Research ArticleAntichronic Gastric Ulcer Effect of Zinc-Baicalin Complex on theAcetic Acid-Induced Chronic Gastric Ulcer Rat Model
Hui Yang 1 Yi Lu2 Xiao-Feng Zeng3 Ling Li1 Rong-Ping Zhang1 Zhong-Kun Ren 2
and Xu Liu 1
1Biomedical Engineering Center Kunming Medical University Kunming 650500 China2Neurosurgery The 1st Affiliated Hospital of Kunming Medical University Kunming 650032 China3School of Forensic Medicine Kunming Medical University Kunming 650500 China
Correspondence should be addressed to Zhong-Kun Ren renzhongkunbio163com and Xu Liu liuxu1956163com
Received 28 February 2018 Revised 11 August 2018 Accepted 2 September 2018 Published 28 October 2018
Academic Editor Haruhiko Sugimura
Copyright copy 2018 Hui Yang et al This is an open access article distributed under the Creative Commons Attribution License whichpermits unrestricted use distribution and reproduction in any medium provided the original work is properly cited
Background Baicalin (BA) has been shown to have anti-inflammatory and antioxidant activity Zinc is a nutrient elementObjective This study is aimed at investigating the antichronic gastric ulcer activity of Zn-Baicalin complex (BA-Zn) and itsrelated mechanisms in an acetic acid-induced gastric ulcer rat model Results The severely ulcerated gastric mucosa of modelrats had lower GSH-Px (5221plusmn 713) and SOD (703plusmn 010) activity and higher MDA (239plusmn 003) content compared to shamrats BA-Zn reduced the gastric ulcer index in a dose-dependent manner significantly increased SOD activity and GSH-Px leveland reduced the MDA content and IL-8 and TNF-α levels in the gastric mucosa BA-Zn (65 and 13mgkg) exerted a greaterantiulcerogenic effect than both BA and zinc-gluconate leading to a reduced ulcer index (1843plusmn 111 1500plusmn 144) decreasedMDA content (133plusmn 007 063plusmn 001) and increased SOD activity (1762plusmn 011 2012plusmn 032) and GSH-Px levels (10212plusmn 91112025plusmn 907) In addition our results from Western blot suggested that BA-Zn (65 and 13mgkg) has a greater antiulcerogeniceffect than both BA and zinc-gluconate Conclusion The BA-Zn complex possesses greater antichronic gastric ulcer propertiescompared to BA and zinc-gluconate due to its ability of oxidation resistance and anti-inflammatory effects
1 Introduction
Peptic ulcers create a serious disease state in humans arecommon worldwide and have an increasing incidence rateGastric ulceration often increases the level of gastric acidsecretion can damage the gastric mucosal barrier and pene-trates the mucus layer [1 2] An ulcer model induced byacetic acid in rats resembles human chronic ulcers in bothpathological features and healing process Therefore thismodel is more promising and useful for researchers toexplore gastric ulcer The pathogenesis of gastric ulcers iscomplex due to multifactorial and complex interactionbetween protective and destructive factors Nonsteroidalanti-inflammatory drugs (NSAIDs) are the most commonlyrecommended medication and are comprehensively used todecrease clinical cases of pain and inflammation [3] How-ever these drugs are known to induce intestinal ulcerations
and hinder ulcer healing [4] Traditional medicinal herbsand plants offer great promise in the treatment of many dis-eases and are an important source of new chemical substanceswith potential therapeutic effects to treat several diseases
Chemical moieties isolated from plants have a long his-tory of beneficial effects for treating ulcers Baicalin (BA) is aflavonoid compound extracted and purified from the Chinesemedicinal herb Scutellaria baicalensisGeorgi which has beendemonstrated to have antiulcer antipyretic anti-inflamma-tory analgesic anticancer antioxidant and wound healingproperties [5ndash10] Zinc is essential for the maintenance ofhuman cell functions Moreover it is reported that zinc canpromote the healing of small intestinal mucosal damageZinc loss could significantly impair wound healing [11] Zincis also a free radical scavenger and anti-inflammatory agentwhich can halt the progression of gastrointestinal diseaseand interrupt the associated inflammatory processes Zinc
HindawiGastroenterology Research and PracticeVolume 2018 Article ID 1275486 9 pageshttpsdoiorg10115520181275486
complexes have always exerted potent antiulcer activityZinc-carnosine is a common antiulcer drug used in the treat-ment of gastric ulcers in Japan [12] However there is littleresearch about the antichronic gastric ulcer ability of BA-Zn and its related mechanism is still unclear
It was reported that reactive oxygen species (ROS) playedan important role in digestive disorders [13 14] In additionoxygen free radical production and lipid peroxidation play anessential function in the development of gastric ulceration[15 16] Moreover alterations to the antioxidant defense sys-tem in ulcerative disorders suggest a vital role for free radicalsin ulcerations induced by acetic acid Inflammatory cytokinessuch as IL-8 can also influence gastric ulcer healing [17 18]Thus inflammatory cytokines are regarded as indicators ofgastric ulcers
In this study we investigated whether the BA-Zn com-plex possesses antiulcer activity in a rat model of aceticacid-induced chronic gastric ulcer through free radical scav-enging and anti-inflammatory activity
2 Materials and Methods
21 Chemicals andReagentsBaicalin (BAMw 46438)waspur-chased from Wanfang Chemical Company (Yunnan China)The zinc complex of baicalin (BA-Zn Zn(C21H17O11)(CH3-COO)sdot35H2O Mw 632) was synthesized by the College ofPharmacy of Kunming Medical University The LD50 ofthe zinc-baicalin (BA-Zn) complex is 476 gkgmiddotbw and theED50 is 1042mgkg IL-8 TNF-α SOD GSH-Px andMDA kits were purchased from Nanjing Jiancheng ResearchInstitute (Nanjing China)
22 Preparation of BA-Zn 500ml of water was added to 50 gof BA in a beaker stirring constantly and making this into asuspension liquid heating to 55degC at pH65ndash70 then add-ing a zinc acetate-saturated solution and mixing fully Thiswas then cooled to room temperature and filtered for redprecipitation This was then washed with 75 ethanol andddH2O2 respectively and finally drying these precipitationat 60degC
23 Animals Healthy male Sprague-Dawley rats 7weeks oldand weighing 180ndash200 g were from the experimental animalcenter of Kunming Medical College (certificate numberSCXK2005-0008) The Animal Ethics Committee agreementnumber is KMMU2015011 The animals were housed on apathogen-free environment with a constant 12h light12 hdark cycle in a temperature-controlled central facility (18ndash22degC) with free access to normal chow and tap water for aweek All procedures were in accordance with the AnimalEthics Committee of Kunming Medical University and theGuide for the Care and Use of Laboratory Animals
24 Experimental Protocol for Ulceration and Healing Ani-mals were divided randomly into eight experimental groupswith 10 animals in each group the sham group (water vehi-cle po (per os)) model group (chronic gastric ulcers) BA-Zn groups (325 65 and 13mgkg BA-Zn po) BA group(46mgkg BA po) zinc-gluconate group (932mgkgpo) and omeprazole group (40mgkg omeprazole po)
Chronic gastric ulcers were induced with acetic acid accord-ing to the method of Okabe et al [19] Briefly the rats wereanesthetized with sodium pentobarbital (30mgkg respec-tively ip (intraperitoneal injection)) and then the abdomenwas opened and the stomach exposed A solution of 80acetic acid (vv 05ml) was instilled into a cylinder (5mmof diameter) that was applied to the serosal surface of thestomach and after 1min was removed by aspiration the areaof contact was washed with sterile saline Forty-eight hoursafter ulcer induction the rats were orally treated with vehicle(sham water 1mgkg) BA (46mgkg) zinc-gluconate(932mgkg) omeprazole (40mgkg) and BA-Zn (32565 13mgkg) once a day for 7days On the day followingthe last treatment all animals were alive Then the animalswere euthanatized by an overdose of pentobarbital sodium(150mgkg ip) and the stomachs were removed andopened for the measurement of the ulcer area (mm2) aslength (mm)timeswidth (mm) The gastric ulcer tissue was usedfor the following tests
25 Histological Preparation A sample obtained from themiddle of the gastric lesion was processed according to theconventional procedure and stained with hematoxylin-eosin The stomachs were removed filled with 5ml of 10formalin and allowed to stand for 5min then these werecut open along the greater curvature The longitudinal andabscissal lengths of the upper opened part of the ulcer weremeasured with a micrometer that was attached to a stereo-scopic microscope and the product of both lengths (mm2)is expressed in terms of the ulcer index (Table 1) After theulcer size was measured the stomach tissue was againimmersed in 10 formalin for 24 h The formalin-fixed tis-sues were then cut so that a small amount of the normal tis-sue surrounding the ulcer remained
26 Hematoxylin and Eosin Staining The stomach tissueswere immediately fixed in 4 paraformaldehyde for 48h at4degC Paraffin sections (5μm) were prepared and then stainedwith hematoxylin and eosin (HE) according to standard pro-cedures Tissue were observed and microphotographedunder a light microscope
27 Detection of SOD Activity GSH-Px MDA IL-8 andTNF-α Levels Gastric tissue from the ulcerated portion ofthe stomach was excised washed with distilled waterchopped and homogenized at 3000 rpm in chilled Tris buffer(10mM pH74) at a concentration of 10 wv Then thehomogenate was centrifuged at 9000timesg at 4degC for 20minand the supernatants were used for the determination ofsuperoxide dismutase (SOD) methylenedioxyamphetamine(MDA) and GSH-Px (glutathione peroxidase) contents aswell as IL-8 and TNF-α expression levels by using the follow-ing detection kits purchased from Nanjing Jiancheng Bio-technology Co Ltd a superoxide dismutase (SOD) assaykit (WST-1 method) (no 20160914) glutathione peroxidase(GSH-Px) assay kit (colorimetric method) (no 20160115)malondialdehyde (MDA) assay kit (TBA method) (no20161130) interleukin-8 assay kit (no 20160815) and tumornecrosis factor-α assay kit (no 20160703) The changes in
2 Gastroenterology Research and Practice
absorbance were determined using a spectrophotometer theresults are expressed as Ul and μmoll for GSH-Px andMDA Umg protein for SOD activity and ngml for IL-8and TNF-α levels
28 Western Blot Analysis Western blot analysis was usedfor the protein expression levels of SOD1 TNF-α andIL-8 Total proteins of tissues were extracted with lysisbuffer (Beyotime China) The insoluble protein lysate wasremoved by centrifugation at 10000timesg for 10min at 4degCTotal proteins were separated by 10 sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE)followed by blocking in 5 skim milk on a PVDF mem-brane The membranes were hybridized with primary anti-bodies (Proteintech USA) for 2 h at 4degC and then withsecondary antibodies (Proteintech USA) for 2 h at roomtemperature The bands were developed using an enhancedchemiluminescence (ECL) detection system (EMDMilliporeUSA) for horseradish peroxidase (HRP) The relativeamounts of the various proteins were analyzed β-Actin wasused as a loading control The results were quantified usingImageJ software
29 Statistical Analysis All the results were expressed asmeanplusmn SD Statistical comparisons were made betweendrug-treated groups and acetic acid groups The data was sta-tistically analyzed by one-way analysis of variance (ANOVA)(Tukeyrsquos post hoc test) using GraphPad Prism softwareversion 50a (GraphPad Software Inc California USA)P lt 0 05 was considered to be statistically significant
3 Results
31 BA-Zn Protects against Acetic Acid-Induced GastricLesions The molecular formula of BA-Zn isZn(C21H17O11)(CH3COO)sdot35H2O and it has a molecularweight of 632 gmol (Figure 1) The macroscopic appearanceof the gastric tissue is shown in Figure 2 Rats treated withonly water (Figure 2(a)) showed a normal glandular stomachFigure 2(b) shows the deep ulceration and severe edematouschanges in the gastric mucosa of the model group that wasinduced with 80 acetic acid and treated with water dailyBy contrast rats treated with BA-Zn (325 65 or 13mg
kg) or BA zinc-gluconate or omeprazole showed less severeulceration and less edema in the gastric mucosa induced by80 acetic acid (Figures 2(c)ndash2(h))
As shown in Figure 3(a) the microscopic histologicalappearance of the gastric tissue and the normal gastric epi-thelium was observed in the sham group The applicationof acetic acid induced the disruption of the superficial regionof the gastric gland with loss of epithelial cells as well as pro-nounced edema of the submucosa and degradation of themucosa in the model group (Figure 3(b))
BA-Zn (325 65 and 13mgkg) and omeprazole mark-edly reduced the severity of gastric ulcers (swelling destruc-tion and extensive destruction on the surface of theepithelium) and promoted marginal regeneration of the epi-thelium compared to the model group (Figures 3(c)ndash3(e) and3(h)) In the BA (46mgkg) and zinc-gluconate- (932mgkg) treated groups the severity of the gastric ulcers was alsoinhibited (Figures 3(f) and 3(g))
In all animals from all the groups that survived the lon-gitudinal and abscissal lengths of the upper opened part ofthe ulcer were measured with a micrometer that wasattached to a stereoscopic microscope and the product ofboth lengths (mm2) was expressed in terms of the ulcerindex As shown in Table 1 the sham group showed noulcer index and administration of BA-Zn at doses of 32565 and 13mgkg decreased the gastric ulcer index to2494plusmn 200 (P lt 0 05) 1843plusmn 111 (P lt 0 001) and 1500plusmn144mm2 (P lt 0 001) (120 350 and 471 protectionrespectively) compared to the ulcer index of the model groupwhich was 2835plusmn 327mm2 BA (46mgkg) reduced thegastric ulcer index to 2438plusmn 230 (P lt 0 05) compared tothat of the model group Zinc-gluconate (932mgkg) alsoreduced the gastric ulcer index to 2371plusmn 200 (P lt 0 05)compared to that of the model group Moreover zinc-gluconate had a higher gastric ulcer index than the BA-Zngroup (65 and 13mgkg P lt 0 001 respectively) It indicatedthat BA-Zn (65 and 13mgkg) has a stronger healing effectthan zinc-gluconate Omeprazole (40mgkg) the positivecontrol drug demonstrated a potency for reducing the gas-tric ulcer index (1535plusmn 122mm2 P lt 0 001 compared tothe model group) BA-Zn (13mgkg) showed the bestpotency for reducing the gastric ulcer index which was thesame as omeprazole
Table 1 Effect of BA-Zn on oxidant stress in rat mucosa induced by acetic acid
Group (mgkg) Ulcer index (mm2) SOD (Umg) MDA (μmoll) GSH-Px (Ul)
Omeprazole 4 1535plusmn 122lowastlowastlowast 1932plusmn 009lowastlowastlowast 100plusmn 011lowastlowastlowast 10712plusmn 905lowastlowastlowastlowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
3Gastroenterology Research and Practice
32 BA-Zn Suppressed Oxidative Stress in Acetic Acid-Induced Gastric Tissue of Rats Increased oxidative stresswas shown in the ulcerated gastric mucosa of the modelgroup and this group also had significantly decreased SODand GSH-Px activities and an increased level of lipid peroxi-dation (MDA) content compared to those of the sham group(P lt 0 001)
As shown in Table 1 SOD activity in the mucosa of themodel group was significantly lower (703plusmn 010Umg pro-tein) than in the sham group (2209plusmn 009Umg proteinP lt 0 001) BA-Zn treatment at 65 and 13mgkg significantlyincreased the SOD activity to 1762plusmn 011 and 2012plusmn 032Umg protein (P lt 0 001 and P lt 0 001) respectively comparedto that of the model group (703plusmn 010Umg protein) More-over the administration of 65 and 13mgkg BA-Zn led tohigher SOD activity than did the administration of BA(1762plusmn 011 and 2012plusmn 032 vs 1209plusmn 013Umg proteinP lt 0 05 and P lt 0 01) and these also markedly increasedSOD activity than that of the zinc-gluconate group (907plusmn033Umg protein P lt 0 001) It indicated that BA-Zn hasa stronger antioxidative effect than BA and zinc-gluconateZinc-gluconate (932mgkg) significantly increased SODactivity to 907plusmn 033Umg protein (P lt 0 05) compared tothat of the model group (703plusmn 010Umg protein) Omep-razole (40mgkg) demonstrated an increase in SOD activity(1932plusmn 009Umg protein P lt 0 001 compared to that ofthe model group)
GSH-Px levels in the gastric mucosa of the model groupwere significantly lower than in the sham group (5221plusmn713 vs 13609plusmn 909Ul P lt 0 001) Administration of 65and 13mgkg BA-Zn significantly increased the GSH-Pxlevel in a dose-dependent manner (P lt 0 001 and P lt 0 001respectively compared to that of the model group) More-over the administration of 65 and 13mgkg BA-Zn led toincreased GSH-Px activity compared to that of the BA group(10212plusmn 911 and12025plusmn 907 vs 8507plusmn 711UlP lt 0 05)and the administration of 65 and 13mgkg BA-Zn alsomarkedly increased GSH-Px activity compared to that ofthe zinc-gluconate group (8035plusmn 677Ul P lt 0 001) Itindicated that BA-Zn has a stronger antioxidative effectthan BA and zinc-gluconate Zinc-gluconate (932mgkg)
significantly increased GSH-Px activity to 8035plusmn 677Ul(P lt 0 05) compared to that of the model group (5221plusmn713Ul) Omeprazole (40mgkg) demonstrated an increasein GSH-Px activity (10712plusmn 905Ul P lt 0 001 comparedto that of the model group)
The inhibitory effects of BA-Zn on lipid peroxidation(MDA) are shown in Table 1 The MDA content in thegastric mucosa of the model group was higher than in thesham group (239plusmn 003 vs 091plusmn 006μmoll P lt 0 001)Treatment with 325 65 and 13mgkg BA-Zn significantlydecreased the MDA content to 175plusmn 007 133plusmn 007 and063plusmn 001μmoll (P lt 0 01 P lt 0 001 and P lt 0 001respectively compared to that of the model group) More-over the administration of 325 65 and 13mgkg BA-Znled to lower MDA activity than BA (175plusmn 007 133plusmn007 and 063plusmn 901 vs 354plusmn 004μmoll P lt 0 05) andthe zinc-gluconate group (200plusmn 012μmoll P lt 0 001)indicating that BA-Zn had a stronger antioxidative effectthan BA and zinc-gluconate Zinc-gluconate (932mgkg)showed a decrease in MDA content (200plusmn 012μmollP lt 0 05 compared to that the model group) Omeprazole(40mgkg) also demonstrated a decrease in MDA con-tent (100plusmn 011μmoll P lt 0 001 compared to that of themodel group)
33 Effect of BA-Zn on the Concentration of TNF-α and IL-8As shown in Table 2 the level of TNF-α in the model groupwas significantly higher than in the sham group (273plusmn 010vs 072plusmn 009 ngml P lt 0 001) The administration of 32565 and 13mgkg BA-Zn significantly decreased the TNF-αconcentration in a dose-dependent manner (195plusmn 006162plusmn 011 and 112plusmn 032 P lt 0 05 P lt 0 001 and P lt0 001 respectively compared to that of the model group)Zinc-gluconate (932mgkg) demonstrated a decreased TNF-α level (200plusmn011ngml P lt 0 05 compared to that of themodel group) Administration of 65 and 13mgkg BA-Zn sig-nificantly decreased the TNF-α concentration compared to thatof the zinc-gluconate group (200plusmn011ngml P lt 0 001)Omeprazole (40mgkg) demonstrated a decreased TNF-αconcentration (132plusmn 009 ngml P lt 0 001 compared to thatof the model group)
CH3
O
OO
O
OO
O
35H2OOH
OH
OH
OH
HO
OZn
Figure 1 Structural formula of BA-Zn
4 Gastroenterology Research and Practice
The level of IL-8 in the model group was significantlyhigher than in the sham group (069plusmn 003 vs 021plusmn006 ngml P lt 0 01) Administration of 325 65 and13mgkg BA-Zn significantly decreased the IL-8 level in adose-dependent manner (036plusmn 007 033plusmn 007 and 029plusmn001 P lt 0 01 P lt 0 01 and P lt 0 001 respectively com-pared to that of the model group) Zinc-gluconate (932mgkg) demonstrated a decreased IL-8 level (060plusmn 001 ngmlP lt 0 05 compared to that of the model group) Administra-tion of 325 65 and 13mgkg BA-Zn significantly decreasedthe IL-8 concentration compared to that of the zinc-gluconate group (060plusmn 001 ngml P lt 0 001) Omeprazole(40mgkg) also demonstrated a decreased IL-8 level (045plusmn001 ngml P lt 0 05 compared to the model group)
To further demonstrate the effect of BA-Zn on the con-centration of SOD TNF-α and IL-8 in the above groupsWestern blot assays were used to detect the expression levelsof these proteins In Figure 4(a) and 4(b) we reveal thatBA-Zn treatment significantly increased SOD expression
compared to that in the model and zinc-gluconate groupsBA-Zn also significantly decreased the expression of TNF-αand IL-8 compared to that in the model and zinc-gluconategroups In summary the above results indicate that BA-Znhad better antioxidative and anti-inflammatory effects thanboth BA and zinc-gluconate
4 Discussion
Gastric ulcer is a common dysfunction of the digestive sys-tem and an increasing number of people worldwide are suf-fering damage from ulcers The acetic acid-induced ulcermodel resembles human chronic ulcers in both pathologicalfeatures and aspects of the healing process [20 21] thus itis themostusefulmodel forus tousewhen investigating gastriculcers Previous studies have demonstrated that experimentalgastric ulcers have many histological and ultrastructuralabnormalities including a reduced height marked dilationof gastric glands and increased connective tissue that may
(a) (b) (c)
(d) (e) (f)
(g) (h)
Figure 2 Appearances of acetic acid-induced gastric ulcers in different groups (a) the sham group treated daily with water (b) an ulcerationfrom the model group induced by acetic acid (cndashe) an ulceration from the BA-Zn group induced by acetic acid and treated daily with BA-Zn(325 65 and 13mgkg po) (f) an ulceration from the BA group induced by acetic acid and treated daily with BA (46mgkg po) (g) anulceration from the zinc-gluconate group induced by acetic acid and treated daily with zinc-gluconate (932mgkg po) and (h) an ulcerationfrom the omeprazole group induced by acetic acid and treated daily with omeprazole (40mgkg po) Black arrows indicate ulcer location
5Gastroenterology Research and Practice
interfere with the mucosal defense system and cause ulcerrecurrence with some ulcerogenic factors [22 23]
In recent years chemical drugs used for the treatmentof gastric ulcers have induced many side effects Recentlynewly developed drugs with herbal origins may offerreduced side effects compared with chemical drugs [24]
In folk knowledge medicinal plants have been used forthe treatment of various disorders More and more medic-inal plants with various therapeutic properties especially forthe treatment of gastritis and gastric ulcers have been identi-fied [25ndash27] However few traditional Chinese medicinalplants for gastric ulcer treatment have been studied Cur-rently because of the lack of effective and applicable pharma-cological treatments for gastric ulcer more and more peoplehave focused on traditional medicines The investigation ofthe therapeutic functions of traditional medicinal herbs ingastric ulcer offer promising potential
Scutellaria baicalensis is a popular medicinal herb used intraditional Chinese medicine and it is used for the treatmentof high fevers ulcers inflammation and even cancer Themain bioactive flavonoids in Scutellaria baicalensis includebaicalein baicalin (BA) (baicalein-7-glucuronide) wogoninwogonoside (wogonin-7-glucuronide) oroxylin A and orox-ylin A-7-glucuronide Scutellaria baicalensis and its flavoneshave been studied for their various pharmacological activi-ties including anti-inflammatory [28] antibacterial [29]neuroprotective [30] anticonvulsant [31] antiviral [32]antitumor [33] and antioxidant [34] activities BA is themostpopular bioactive flavonoid for treating ulcers However the
(a) (b) (c)
(d) (e) (f)
(g) (h)
Figure 3 Photomicrographs of acetic acid-induced gastric ulcers from different groups (a) sham group (b) HE staining of the model groupinduced by acetic acid (cndashe) HE staining of the BA-Zn group induced by acetic acid and treated daily with BA-Zn (325 65 and 13mgkgpo) (f) HE staining of the BA group induced by acetic acid and treated daily with BA (46mgkg po) (g) HE staining of the zinc-gluconategroup induced by acetic acid and treated daily with zinc-gluconate (932mgkg po) and (h) HE staining of the omeprazole group inducedby acetic acid and treated daily with omeprazole (40mgkg po) The HE stained slides were visualized under a bright field microscopewith 20x magnification
Table 2 Concentration of TNF-α and IL-8 in rat mucosa inducedby acetic acid
Omeprazole 4 132plusmn 009lowastlowastlowast 045plusmn 001lowastlowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
6 Gastroenterology Research and Practice
antichronic gastric ulcer effects of BA alone or in complexhave not yet been elucidated
In this paper we examined the effects of BA-Zn BA andzinc-gluconate and related mechanisms on gastric ulcer heal-ing in an acetic acid-induced gastric ulcer rat model It hasbeen reported that zinc-gluconate has a protective effect ongastric ulcers [35] Acetic acid induces a state of acute stressin the gastric mucosa subsequently inducing gastric ulcersMoreover acetic acid-induced gastric ulceration leads tochronic oxidative stress with decreased SOD activity andGSH-Px expression levels and increased lipid peroxidation(MDA) It is well known that SOD GSH-Px and MDA playimportant roles in protecting the gastric mucosa against var-ious damaging agents [36 37] GSH-Px also plays an impor-tant role in protecting against oxidative gastric mucosalinjury [38] MDA is currently regarded as a reliable indexof ROS-induced mucosal injury [39] Therefore the detec-tion of SOD GSH-Px and MDA contents can reflect andindicate the level of oxidative stress In addition increasedconcentrations of TNF-α and IL-8 were detected in the ulcer-ated gastric mucosa BA-Zn (13mgkg) significantly acceler-ated the healing of gastric ulcers through an increase in SODand GSH-Px activity and a decrease in MDA IL-8 and TNF-α contents We also detected the levels of SOD IL-8 andTNF-α by Western blot We found that BA-Zn significantlyaccelerated ulcer healing by decreasing oxidative stress andattenuating inflammation In our results zinc-gluconate alsohas a protective effect on gastric ulcers but BA-Zn has much
stronger protective and healing abilities in gastric ulcers Onthe basis of our data BA-Zn (13mgkg) has greater antigas-tric ulcer abilities than either BA or zinc-gluconate
Collectively BA-Zn presents important ulcer-healingproperties in the model of chronic ulcer induced by aceticacid in rats Omeprazole is one of the most popular drugsused for the therapeutic control of gastroduodenal ulcers inhumans In our work BA-Zn also exerted an antiulcerogeniceffect similar to that of omeprazole against the developmentof acetic acid-induced gastric ulcers in rats using antioxidantand anti-inflammatory abilities Therefore the BA-Zn com-plex may become a potential and promising drug for thetreatment of human gastroduodenal ulcers In summaryour study indicates that BA-Zn promotes ulcer healing bydecreasing oxidative stress and attenuating inflammation inan acetic acid-induced gastric ulcer rat model Howeveradditional studies are needed to explore the novel mecha-nisms of BA-Zn and determine whether other mechanismsare also involved in the antiulcer effects of this complex
5 Conclusion
In conclusion BA-Zn facilitates the healing of acetic-inducedchronic ulcers in rats through its antioxidant and anti-inflammatory properties The results of this study provide afoundation for the clinical application of BA-Zn in the treat-ment of gastroduodenal ulcers
SOD
IL-8
TNF-훼
훽-Actin
Sham Model BA O325
BA-Zn (mgkg)
Z1365
(a)
SOD25
2015100500
Sham
Mod
el BA 325 6
5
BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Sham
Mod
el BA 325 6
5BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Sham
Mod
el BA 325 6
5
BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Prot
ein
leve
l
20
15
10
05
00
Prot
ein
leve
l20
15
10
05
00
Prot
ein
leve
l
IL-8 TNF-훼
(b)
Figure 4 Western blot analysis of SOD TNF-α and IL-8 expression (a) The protein expression levels of SOD TNF-α and IL-8 wereanalyzed by Western blot analysis β-Actin was used as a loading control (b) Quantification of SOD TNF-α and IL-8 protein expressionlevels using ImageJ software Z zinc-gluconate O omeprazole lowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
7Gastroenterology Research and Practice
Data Availability
The data used to support the findings of this study are avail-able from the corresponding author upon request
Conflicts of Interest
The authors declare that there are no conflicts of interest andno financial conflicts regarding the publication of this paper
Authorsrsquo Contributions
This study was designed by Xu Liu Experimental work wasdone by Hui Yang Zhong-Kun Ren Yi Lu Xiao-Feng Zengand Ling Li The first draft of this paper was written by HuiYang and reviewed by Xu Liu and Rong-Ping ZhangZhong-Kun Ren and Yi Lu reviewed the methodology andresults All authors reviewed and approved the final version
Acknowledgments
The present study was supported by the Yunnan AppliedBasic Research Projects (Grant no 2005C00092)
References
[1] J L Goldstein J Aisenberg F Lanza et al ldquoA multicenterrandomized double-blind active-comparator placebo-con-trolled parallel-group comparison of the incidence of endo-scopic gastric and duodenal ulcer rates with valdecoxib ornaproxen in healthy subjects aged 65 to 75 yearsrdquo ClinicalTherapeutics vol 28 no 3 pp 340ndash351 2006
[2] G H Heeba M K A Hassan and R S Amin ldquoGastroprotec-tive effect of simvastatin against indomethacin-induced gastriculcer in rats role of nitric oxide and prostaglandinsrdquo EuropeanJournal of Pharmacology vol 607 no 1ndash3 pp 188ndash193 2009
[3] P A Gladding M W I Webster H B Farrell I S L ZengR Park and N Ruijne ldquoThe antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacody-namic interaction with aspirin in healthy volunteersrdquo TheAmerican Journal of Cardiology vol 101 no 7 pp 1060ndash1063 2008
[4] A Lanas M A Perez-Aisa F Feu et al ldquoA nationwide studyof mortality associated with hospital admission due to severegastrointestinal events and those associated with nonsteroidalantiinflammatory drug userdquo The American Journal of Gastro-enterology vol 100 no 8 pp 1685ndash1693 2005
[5] B Cryer and K W Mahaffey ldquoGastrointestinal ulcers role ofaspirin and clinical outcomes pathobiology diagnosis andtreatmentrdquo Journal of Multidisciplinary Healthcare vol 7pp 137ndash146 2014
[6] J Lu J S Wang and L Y Kong ldquoAnti-inflammatory effects ofHuang-Lian-Jie-Du decoction its two fractions and four typi-cal compoundsrdquo Journal of Ethnopharmacology vol 134no 3 pp 911ndash918 2011
[7] J M Hwang T H Tseng Y Y Tsai et al ldquoProtective effects ofbaicalein on tert-butyl hydroperoxide-induced hepatic toxicityin rat hepatocytesrdquo Journal of Biomedical Science vol 12no 2 pp 389ndash397 2005
[8] J Dou L Chen G Xu et al ldquoEffects of baicalein on Sendaivirus in vivo are linked to serum baicalin and its inhibition
of hemagglutinin-neuraminidaserdquo Archives of Virologyvol 156 no 5 pp 793ndash801 2011
[9] M Y Yun J H Yang D K Kim et al ldquoTherapeutic effects ofbaicalein on atopic dermatitis-like skin lesions of NCNgamice induced by Dermatophagoides pteronyssinusrdquo Interna-tional Immunopharmacology vol 10 no 9 pp 1142ndash11482010
[10] J H Liu H Wann M M Chen et al ldquoBaicalein signifi-cantly protects human retinal pigment epithelium cellsagainst H2O2-induced oxidative stress by scavenging reac-tive oxygen species and downregulating the expression ofmatrix metalloproteinase-9 and vascular endothelial growthfactorrdquo Journal of Ocular Pharmacology and Therapeuticsvol 26 no 5 pp 421ndash429 2010
[11] P D Zalewski A Q Truong-Tran D Grosser L JayaramC Murgia and R E Ruffin ldquoZinc metabolism in airway epi-thelium and airway inflammation basic mechanisms and clin-ical targets A reviewrdquo Pharmacology amp Therapeutics vol 105no 2 pp 127ndash149 2005
[12] M Odashima M Otaka M Jin et al ldquoZinc L-carnosine pro-tects colonic mucosal injury through induction of heat shockprotein 72 and suppression of NF-κB activationrdquo Life Sciencesvol 79 no 24 pp 2245ndash2250 2006
[13] A Bhattacharyya R Chattopadhyay S Mitra and S E CroweldquoOxidative stress an essential factor in the pathogenesis of gas-trointestinal mucosal diseasesrdquo Physiological Reviews vol 94no 2 pp 329ndash354 2014
[14] L Chanudom and J Tangpong ldquoAnti-inflammation propertyof Syzygium cumini (L) Skeels on indomethacin-inducedacute gastric ulcerationrdquo Gastroenterology Research and Prac-tice vol 2015 Article ID 343642 12 pages 2015
[15] L M da Silva A Allemand D A G B Mendes et al ldquoEtha-nolic extract of roots from Arctium lappa L accelerates thehealing of acetic acid-induced gastric ulcer in rats involve-ment of the antioxidant systemrdquo Food and Chemical Toxicol-ogy vol 51 pp 179ndash187 2013
[16] S K Jaiswal C V Rao B Sharma P Mishra S Das andM KDubey ldquoGastroprotective effect of standardized leaf extractfrom Argyreia speciosa on experimental gastric ulcers in ratsrdquoJournal of Ethnopharmacology vol 137 no 1 pp 341ndash3442011
[17] A A El-Fakhry M A El-Daker R I Badr et al ldquoAssociationof the CagA gene positive Helicobacter pylori and tissue levelsof interleukin-17 and interleukin-8 in gastric ulcer patientsrdquoThe Egyptian Journal of Immunology vol 19 no 1 pp 51ndash62 2012
[18] Y W Yin A M Hu Q Q Sun et al ldquoAssociation betweeninterleukin-8 gene minus251 TA polymorphism and the risk ofpeptic ulcer disease a meta-analysisrdquo Human Immunologyvol 74 no 1 pp 125ndash130 2013
[19] S Okabe J L A Roth and C J Pfeiffer ldquoA method for exper-imental penetrating gastric and duodenal ulcers in ratsObservations on normal healingrdquo The American Journal ofDigestive Diseases vol 16 no 3 pp 277ndash284 1971
[20] K Takagi S Okabe and R Saziki ldquoA newmethod for the pro-duction of chronic gastric ulcer in rats and the effect of severaldrugs on its healingrdquo Japanese Journal of Pharmacologyvol 19 no 3 pp 418ndash426 1969
[21] S Okabe and K Amagase ldquoAn overview of acetic acid ulcermodelsmdashthe history and state of the art of peptic ulcerresearchrdquo Biological amp Pharmaceutical Bulletin vol 28no 8 pp 1321ndash1341 2005
8 Gastroenterology Research and Practice
[22] A Tarnawski J Stachura W J Krause T G Douglass andH Gergely ldquoQuality of gastric ulcer healing a new emerg-ing conceptrdquo Journal of Clinical Gastroenterology vol 13Supplement 1 pp S42ndashS47 1991
[23] A S Tarnawski ldquoCellular and molecular mechanisms of gas-trointestinal ulcer healingrdquo Digestive Diseases and Sciencesvol 50 Supplement 1 pp S24ndashS33 2005
[24] M Arun and V V Asha ldquoGastroprotective effect of Dodonaeaviscosa on various experimental ulcer modelsrdquo Journal of Eth-nopharmacology vol 118 no 3 pp 460ndash465 2008
[25] A Alkofahi and A H Atta ldquoPharmacological screening of theanti-ulcerogenic effects of some Jordanian medicinal plants inratsrdquo Journal of Ethnopharmacology vol 67 no 3 pp 341ndash345 1999
[26] S Khennouf H Benabdallah K Gharzouli et al ldquoEffect oftannins from Quercus suber and Quercus coccifera leaves onethanol-induced gastric lesions in micerdquo Journal of Agricul-tural and Food Chemistry vol 51 no 5 pp 1469ndash1473 2003
[27] S Bhattacharya S R Chaudhuri S Chattopadhyay and S KBandyopadhyay ldquoHealing properties of some Indian medici-nal plants against indomethacin-induced gastric ulceration ofratsrdquo Journal of Clinical Biochemistry and Nutrition vol 41no 2 pp 106ndash114 2007
[28] B Q Li T Fu W H Gong et al ldquoThe flavonoid baicalinexhibits anti-inflammatory activity by binding to chemo-kinesrdquo Immunopharmacology vol 49 no 3 pp 295ndash3062000
[29] J Wu D Hu and K X Wang ldquoStudy of Scutellaria baicalensisand Baicalin against antimicrobial susceptibility of Helicobac-ter pylori strains in vitrordquo Zhong yao cai = Zhongyaocai = Jour-nal of Chinese Medicinal Materials vol 31 no 5 pp 707ndash7102008
[30] A M Y Lin Y H Ping G F Chang et al ldquoNeuroprotectiveeffect of oral SB remedy (Scutellaria baicalensis Georgi andBupleurum scorzonerifolfium Willd) on iron-induced neuro-degeneration in the nigrostriatal dopaminergic system of ratbrainrdquo Journal of Ethnopharmacology vol 134 no 3pp 884ndash891 2011
[31] S Y Yoon I C dela Pena C Y Shin et al ldquoConvulsion-related activities of Scutellaria flavones are related to the 57-dihydroxyl structuresrdquo European Journal of Pharmacologyvol 659 no 2-3 pp 155ndash160 2011
[32] L Chen J Dou Z Su et al ldquoSynergistic activity of baicaleinwith ribavirin against influenza A (H1N1) virus infections incell culture and in micerdquo Antiviral Research vol 91 no 3pp 314ndash320 2011
[33] M Li-Weber ldquoNew therapeutic aspects of flavones the anti-cancer properties of Scutellaria and its main active constitu-ents wogonin baicalein and baicalinrdquo Cancer TreatmentReviews vol 35 no 1 pp 57ndash68 2009
[34] D E Shieh L T Liu and C C Lin ldquoAntioxidant and free rad-ical scavenging effects of baicalein baicalin and wogoninrdquoAnticancer Research vol 20 no 5A pp 2861ndash2865 2000
[35] B Bandyopadhyay and S K Bandyopadhyay ldquoProtectiveeffect of zinc gluconate on chemically induced gastric ulcerrdquoThe Indian Journal of Medical Research vol 106 pp 27ndash321997
[36] S S Poulsen ldquoOn the role of epidermal growth factor in thedefence of the gastroduodenal mucosardquo Scandinavian Journalof Gastroenterology vol 128 pp 20ndash23 1987
[37] S Kwiecień T Brzozowski P C H Konturek and S JKonturek ldquoThe role of reactive oxygen species in action ofnitric oxide-donors on stress-induced gastric mucosal lesionsrdquoJournal of Physiology and Pharmacology vol 53 4 Part 2pp 761ndash773 2002
[38] I Chattopadhyay U Bandyopadhyay K Biswas P Maity andR K Banerjee ldquoIndomethacin inactivates gastric peroxidase toinduce reactive-oxygen-mediated gastric mucosal injury andcurcumin protects it by preventing peroxidase inactivationand scavenging reactive oxygenrdquo Free Radical Biology amp Med-icine vol 40 no 8 pp 1397ndash1408 2006
[39] M Maes P Ruckoanich Y S Chang N Mahanonda andM Berk ldquoMultiple aberrations in shared inflammatory andoxidative amp nitrosative stress (IOampNS) pathways explain theco-association of depression and cardiovascular disorder(CVD) and the increased risk for CVD and due mortality indepressed patientsrdquo Progress in Neuro-Psychopharmacologyand Biological Psychiatry vol 35 no 3 pp 769ndash783 2011
Computational and Mathematical Methods in Medicine
Hindawiwwwhindawicom Volume 2018
Behavioural Neurology
OphthalmologyJournal of
Hindawiwwwhindawicom Volume 2018
Diabetes ResearchJournal of
Hindawiwwwhindawicom Volume 2018
Hindawiwwwhindawicom Volume 2018
Research and TreatmentAIDS
Hindawiwwwhindawicom Volume 2018
Gastroenterology Research and Practice
Hindawiwwwhindawicom Volume 2018
Parkinsonrsquos Disease
Evidence-Based Complementary andAlternative Medicine
Volume 2018Hindawiwwwhindawicom
Submit your manuscripts atwwwhindawicom
complexes have always exerted potent antiulcer activityZinc-carnosine is a common antiulcer drug used in the treat-ment of gastric ulcers in Japan [12] However there is littleresearch about the antichronic gastric ulcer ability of BA-Zn and its related mechanism is still unclear
It was reported that reactive oxygen species (ROS) playedan important role in digestive disorders [13 14] In additionoxygen free radical production and lipid peroxidation play anessential function in the development of gastric ulceration[15 16] Moreover alterations to the antioxidant defense sys-tem in ulcerative disorders suggest a vital role for free radicalsin ulcerations induced by acetic acid Inflammatory cytokinessuch as IL-8 can also influence gastric ulcer healing [17 18]Thus inflammatory cytokines are regarded as indicators ofgastric ulcers
In this study we investigated whether the BA-Zn com-plex possesses antiulcer activity in a rat model of aceticacid-induced chronic gastric ulcer through free radical scav-enging and anti-inflammatory activity
2 Materials and Methods
21 Chemicals andReagentsBaicalin (BAMw 46438)waspur-chased from Wanfang Chemical Company (Yunnan China)The zinc complex of baicalin (BA-Zn Zn(C21H17O11)(CH3-COO)sdot35H2O Mw 632) was synthesized by the College ofPharmacy of Kunming Medical University The LD50 ofthe zinc-baicalin (BA-Zn) complex is 476 gkgmiddotbw and theED50 is 1042mgkg IL-8 TNF-α SOD GSH-Px andMDA kits were purchased from Nanjing Jiancheng ResearchInstitute (Nanjing China)
22 Preparation of BA-Zn 500ml of water was added to 50 gof BA in a beaker stirring constantly and making this into asuspension liquid heating to 55degC at pH65ndash70 then add-ing a zinc acetate-saturated solution and mixing fully Thiswas then cooled to room temperature and filtered for redprecipitation This was then washed with 75 ethanol andddH2O2 respectively and finally drying these precipitationat 60degC
23 Animals Healthy male Sprague-Dawley rats 7weeks oldand weighing 180ndash200 g were from the experimental animalcenter of Kunming Medical College (certificate numberSCXK2005-0008) The Animal Ethics Committee agreementnumber is KMMU2015011 The animals were housed on apathogen-free environment with a constant 12h light12 hdark cycle in a temperature-controlled central facility (18ndash22degC) with free access to normal chow and tap water for aweek All procedures were in accordance with the AnimalEthics Committee of Kunming Medical University and theGuide for the Care and Use of Laboratory Animals
24 Experimental Protocol for Ulceration and Healing Ani-mals were divided randomly into eight experimental groupswith 10 animals in each group the sham group (water vehi-cle po (per os)) model group (chronic gastric ulcers) BA-Zn groups (325 65 and 13mgkg BA-Zn po) BA group(46mgkg BA po) zinc-gluconate group (932mgkgpo) and omeprazole group (40mgkg omeprazole po)
Chronic gastric ulcers were induced with acetic acid accord-ing to the method of Okabe et al [19] Briefly the rats wereanesthetized with sodium pentobarbital (30mgkg respec-tively ip (intraperitoneal injection)) and then the abdomenwas opened and the stomach exposed A solution of 80acetic acid (vv 05ml) was instilled into a cylinder (5mmof diameter) that was applied to the serosal surface of thestomach and after 1min was removed by aspiration the areaof contact was washed with sterile saline Forty-eight hoursafter ulcer induction the rats were orally treated with vehicle(sham water 1mgkg) BA (46mgkg) zinc-gluconate(932mgkg) omeprazole (40mgkg) and BA-Zn (32565 13mgkg) once a day for 7days On the day followingthe last treatment all animals were alive Then the animalswere euthanatized by an overdose of pentobarbital sodium(150mgkg ip) and the stomachs were removed andopened for the measurement of the ulcer area (mm2) aslength (mm)timeswidth (mm) The gastric ulcer tissue was usedfor the following tests
25 Histological Preparation A sample obtained from themiddle of the gastric lesion was processed according to theconventional procedure and stained with hematoxylin-eosin The stomachs were removed filled with 5ml of 10formalin and allowed to stand for 5min then these werecut open along the greater curvature The longitudinal andabscissal lengths of the upper opened part of the ulcer weremeasured with a micrometer that was attached to a stereo-scopic microscope and the product of both lengths (mm2)is expressed in terms of the ulcer index (Table 1) After theulcer size was measured the stomach tissue was againimmersed in 10 formalin for 24 h The formalin-fixed tis-sues were then cut so that a small amount of the normal tis-sue surrounding the ulcer remained
26 Hematoxylin and Eosin Staining The stomach tissueswere immediately fixed in 4 paraformaldehyde for 48h at4degC Paraffin sections (5μm) were prepared and then stainedwith hematoxylin and eosin (HE) according to standard pro-cedures Tissue were observed and microphotographedunder a light microscope
27 Detection of SOD Activity GSH-Px MDA IL-8 andTNF-α Levels Gastric tissue from the ulcerated portion ofthe stomach was excised washed with distilled waterchopped and homogenized at 3000 rpm in chilled Tris buffer(10mM pH74) at a concentration of 10 wv Then thehomogenate was centrifuged at 9000timesg at 4degC for 20minand the supernatants were used for the determination ofsuperoxide dismutase (SOD) methylenedioxyamphetamine(MDA) and GSH-Px (glutathione peroxidase) contents aswell as IL-8 and TNF-α expression levels by using the follow-ing detection kits purchased from Nanjing Jiancheng Bio-technology Co Ltd a superoxide dismutase (SOD) assaykit (WST-1 method) (no 20160914) glutathione peroxidase(GSH-Px) assay kit (colorimetric method) (no 20160115)malondialdehyde (MDA) assay kit (TBA method) (no20161130) interleukin-8 assay kit (no 20160815) and tumornecrosis factor-α assay kit (no 20160703) The changes in
2 Gastroenterology Research and Practice
absorbance were determined using a spectrophotometer theresults are expressed as Ul and μmoll for GSH-Px andMDA Umg protein for SOD activity and ngml for IL-8and TNF-α levels
28 Western Blot Analysis Western blot analysis was usedfor the protein expression levels of SOD1 TNF-α andIL-8 Total proteins of tissues were extracted with lysisbuffer (Beyotime China) The insoluble protein lysate wasremoved by centrifugation at 10000timesg for 10min at 4degCTotal proteins were separated by 10 sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE)followed by blocking in 5 skim milk on a PVDF mem-brane The membranes were hybridized with primary anti-bodies (Proteintech USA) for 2 h at 4degC and then withsecondary antibodies (Proteintech USA) for 2 h at roomtemperature The bands were developed using an enhancedchemiluminescence (ECL) detection system (EMDMilliporeUSA) for horseradish peroxidase (HRP) The relativeamounts of the various proteins were analyzed β-Actin wasused as a loading control The results were quantified usingImageJ software
29 Statistical Analysis All the results were expressed asmeanplusmn SD Statistical comparisons were made betweendrug-treated groups and acetic acid groups The data was sta-tistically analyzed by one-way analysis of variance (ANOVA)(Tukeyrsquos post hoc test) using GraphPad Prism softwareversion 50a (GraphPad Software Inc California USA)P lt 0 05 was considered to be statistically significant
3 Results
31 BA-Zn Protects against Acetic Acid-Induced GastricLesions The molecular formula of BA-Zn isZn(C21H17O11)(CH3COO)sdot35H2O and it has a molecularweight of 632 gmol (Figure 1) The macroscopic appearanceof the gastric tissue is shown in Figure 2 Rats treated withonly water (Figure 2(a)) showed a normal glandular stomachFigure 2(b) shows the deep ulceration and severe edematouschanges in the gastric mucosa of the model group that wasinduced with 80 acetic acid and treated with water dailyBy contrast rats treated with BA-Zn (325 65 or 13mg
kg) or BA zinc-gluconate or omeprazole showed less severeulceration and less edema in the gastric mucosa induced by80 acetic acid (Figures 2(c)ndash2(h))
As shown in Figure 3(a) the microscopic histologicalappearance of the gastric tissue and the normal gastric epi-thelium was observed in the sham group The applicationof acetic acid induced the disruption of the superficial regionof the gastric gland with loss of epithelial cells as well as pro-nounced edema of the submucosa and degradation of themucosa in the model group (Figure 3(b))
BA-Zn (325 65 and 13mgkg) and omeprazole mark-edly reduced the severity of gastric ulcers (swelling destruc-tion and extensive destruction on the surface of theepithelium) and promoted marginal regeneration of the epi-thelium compared to the model group (Figures 3(c)ndash3(e) and3(h)) In the BA (46mgkg) and zinc-gluconate- (932mgkg) treated groups the severity of the gastric ulcers was alsoinhibited (Figures 3(f) and 3(g))
In all animals from all the groups that survived the lon-gitudinal and abscissal lengths of the upper opened part ofthe ulcer were measured with a micrometer that wasattached to a stereoscopic microscope and the product ofboth lengths (mm2) was expressed in terms of the ulcerindex As shown in Table 1 the sham group showed noulcer index and administration of BA-Zn at doses of 32565 and 13mgkg decreased the gastric ulcer index to2494plusmn 200 (P lt 0 05) 1843plusmn 111 (P lt 0 001) and 1500plusmn144mm2 (P lt 0 001) (120 350 and 471 protectionrespectively) compared to the ulcer index of the model groupwhich was 2835plusmn 327mm2 BA (46mgkg) reduced thegastric ulcer index to 2438plusmn 230 (P lt 0 05) compared tothat of the model group Zinc-gluconate (932mgkg) alsoreduced the gastric ulcer index to 2371plusmn 200 (P lt 0 05)compared to that of the model group Moreover zinc-gluconate had a higher gastric ulcer index than the BA-Zngroup (65 and 13mgkg P lt 0 001 respectively) It indicatedthat BA-Zn (65 and 13mgkg) has a stronger healing effectthan zinc-gluconate Omeprazole (40mgkg) the positivecontrol drug demonstrated a potency for reducing the gas-tric ulcer index (1535plusmn 122mm2 P lt 0 001 compared tothe model group) BA-Zn (13mgkg) showed the bestpotency for reducing the gastric ulcer index which was thesame as omeprazole
Table 1 Effect of BA-Zn on oxidant stress in rat mucosa induced by acetic acid
Group (mgkg) Ulcer index (mm2) SOD (Umg) MDA (μmoll) GSH-Px (Ul)
Omeprazole 4 1535plusmn 122lowastlowastlowast 1932plusmn 009lowastlowastlowast 100plusmn 011lowastlowastlowast 10712plusmn 905lowastlowastlowastlowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
3Gastroenterology Research and Practice
32 BA-Zn Suppressed Oxidative Stress in Acetic Acid-Induced Gastric Tissue of Rats Increased oxidative stresswas shown in the ulcerated gastric mucosa of the modelgroup and this group also had significantly decreased SODand GSH-Px activities and an increased level of lipid peroxi-dation (MDA) content compared to those of the sham group(P lt 0 001)
As shown in Table 1 SOD activity in the mucosa of themodel group was significantly lower (703plusmn 010Umg pro-tein) than in the sham group (2209plusmn 009Umg proteinP lt 0 001) BA-Zn treatment at 65 and 13mgkg significantlyincreased the SOD activity to 1762plusmn 011 and 2012plusmn 032Umg protein (P lt 0 001 and P lt 0 001) respectively comparedto that of the model group (703plusmn 010Umg protein) More-over the administration of 65 and 13mgkg BA-Zn led tohigher SOD activity than did the administration of BA(1762plusmn 011 and 2012plusmn 032 vs 1209plusmn 013Umg proteinP lt 0 05 and P lt 0 01) and these also markedly increasedSOD activity than that of the zinc-gluconate group (907plusmn033Umg protein P lt 0 001) It indicated that BA-Zn hasa stronger antioxidative effect than BA and zinc-gluconateZinc-gluconate (932mgkg) significantly increased SODactivity to 907plusmn 033Umg protein (P lt 0 05) compared tothat of the model group (703plusmn 010Umg protein) Omep-razole (40mgkg) demonstrated an increase in SOD activity(1932plusmn 009Umg protein P lt 0 001 compared to that ofthe model group)
GSH-Px levels in the gastric mucosa of the model groupwere significantly lower than in the sham group (5221plusmn713 vs 13609plusmn 909Ul P lt 0 001) Administration of 65and 13mgkg BA-Zn significantly increased the GSH-Pxlevel in a dose-dependent manner (P lt 0 001 and P lt 0 001respectively compared to that of the model group) More-over the administration of 65 and 13mgkg BA-Zn led toincreased GSH-Px activity compared to that of the BA group(10212plusmn 911 and12025plusmn 907 vs 8507plusmn 711UlP lt 0 05)and the administration of 65 and 13mgkg BA-Zn alsomarkedly increased GSH-Px activity compared to that ofthe zinc-gluconate group (8035plusmn 677Ul P lt 0 001) Itindicated that BA-Zn has a stronger antioxidative effectthan BA and zinc-gluconate Zinc-gluconate (932mgkg)
significantly increased GSH-Px activity to 8035plusmn 677Ul(P lt 0 05) compared to that of the model group (5221plusmn713Ul) Omeprazole (40mgkg) demonstrated an increasein GSH-Px activity (10712plusmn 905Ul P lt 0 001 comparedto that of the model group)
The inhibitory effects of BA-Zn on lipid peroxidation(MDA) are shown in Table 1 The MDA content in thegastric mucosa of the model group was higher than in thesham group (239plusmn 003 vs 091plusmn 006μmoll P lt 0 001)Treatment with 325 65 and 13mgkg BA-Zn significantlydecreased the MDA content to 175plusmn 007 133plusmn 007 and063plusmn 001μmoll (P lt 0 01 P lt 0 001 and P lt 0 001respectively compared to that of the model group) More-over the administration of 325 65 and 13mgkg BA-Znled to lower MDA activity than BA (175plusmn 007 133plusmn007 and 063plusmn 901 vs 354plusmn 004μmoll P lt 0 05) andthe zinc-gluconate group (200plusmn 012μmoll P lt 0 001)indicating that BA-Zn had a stronger antioxidative effectthan BA and zinc-gluconate Zinc-gluconate (932mgkg)showed a decrease in MDA content (200plusmn 012μmollP lt 0 05 compared to that the model group) Omeprazole(40mgkg) also demonstrated a decrease in MDA con-tent (100plusmn 011μmoll P lt 0 001 compared to that of themodel group)
33 Effect of BA-Zn on the Concentration of TNF-α and IL-8As shown in Table 2 the level of TNF-α in the model groupwas significantly higher than in the sham group (273plusmn 010vs 072plusmn 009 ngml P lt 0 001) The administration of 32565 and 13mgkg BA-Zn significantly decreased the TNF-αconcentration in a dose-dependent manner (195plusmn 006162plusmn 011 and 112plusmn 032 P lt 0 05 P lt 0 001 and P lt0 001 respectively compared to that of the model group)Zinc-gluconate (932mgkg) demonstrated a decreased TNF-α level (200plusmn011ngml P lt 0 05 compared to that of themodel group) Administration of 65 and 13mgkg BA-Zn sig-nificantly decreased the TNF-α concentration compared to thatof the zinc-gluconate group (200plusmn011ngml P lt 0 001)Omeprazole (40mgkg) demonstrated a decreased TNF-αconcentration (132plusmn 009 ngml P lt 0 001 compared to thatof the model group)
CH3
O
OO
O
OO
O
35H2OOH
OH
OH
OH
HO
OZn
Figure 1 Structural formula of BA-Zn
4 Gastroenterology Research and Practice
The level of IL-8 in the model group was significantlyhigher than in the sham group (069plusmn 003 vs 021plusmn006 ngml P lt 0 01) Administration of 325 65 and13mgkg BA-Zn significantly decreased the IL-8 level in adose-dependent manner (036plusmn 007 033plusmn 007 and 029plusmn001 P lt 0 01 P lt 0 01 and P lt 0 001 respectively com-pared to that of the model group) Zinc-gluconate (932mgkg) demonstrated a decreased IL-8 level (060plusmn 001 ngmlP lt 0 05 compared to that of the model group) Administra-tion of 325 65 and 13mgkg BA-Zn significantly decreasedthe IL-8 concentration compared to that of the zinc-gluconate group (060plusmn 001 ngml P lt 0 001) Omeprazole(40mgkg) also demonstrated a decreased IL-8 level (045plusmn001 ngml P lt 0 05 compared to the model group)
To further demonstrate the effect of BA-Zn on the con-centration of SOD TNF-α and IL-8 in the above groupsWestern blot assays were used to detect the expression levelsof these proteins In Figure 4(a) and 4(b) we reveal thatBA-Zn treatment significantly increased SOD expression
compared to that in the model and zinc-gluconate groupsBA-Zn also significantly decreased the expression of TNF-αand IL-8 compared to that in the model and zinc-gluconategroups In summary the above results indicate that BA-Znhad better antioxidative and anti-inflammatory effects thanboth BA and zinc-gluconate
4 Discussion
Gastric ulcer is a common dysfunction of the digestive sys-tem and an increasing number of people worldwide are suf-fering damage from ulcers The acetic acid-induced ulcermodel resembles human chronic ulcers in both pathologicalfeatures and aspects of the healing process [20 21] thus itis themostusefulmodel forus tousewhen investigating gastriculcers Previous studies have demonstrated that experimentalgastric ulcers have many histological and ultrastructuralabnormalities including a reduced height marked dilationof gastric glands and increased connective tissue that may
(a) (b) (c)
(d) (e) (f)
(g) (h)
Figure 2 Appearances of acetic acid-induced gastric ulcers in different groups (a) the sham group treated daily with water (b) an ulcerationfrom the model group induced by acetic acid (cndashe) an ulceration from the BA-Zn group induced by acetic acid and treated daily with BA-Zn(325 65 and 13mgkg po) (f) an ulceration from the BA group induced by acetic acid and treated daily with BA (46mgkg po) (g) anulceration from the zinc-gluconate group induced by acetic acid and treated daily with zinc-gluconate (932mgkg po) and (h) an ulcerationfrom the omeprazole group induced by acetic acid and treated daily with omeprazole (40mgkg po) Black arrows indicate ulcer location
5Gastroenterology Research and Practice
interfere with the mucosal defense system and cause ulcerrecurrence with some ulcerogenic factors [22 23]
In recent years chemical drugs used for the treatmentof gastric ulcers have induced many side effects Recentlynewly developed drugs with herbal origins may offerreduced side effects compared with chemical drugs [24]
In folk knowledge medicinal plants have been used forthe treatment of various disorders More and more medic-inal plants with various therapeutic properties especially forthe treatment of gastritis and gastric ulcers have been identi-fied [25ndash27] However few traditional Chinese medicinalplants for gastric ulcer treatment have been studied Cur-rently because of the lack of effective and applicable pharma-cological treatments for gastric ulcer more and more peoplehave focused on traditional medicines The investigation ofthe therapeutic functions of traditional medicinal herbs ingastric ulcer offer promising potential
Scutellaria baicalensis is a popular medicinal herb used intraditional Chinese medicine and it is used for the treatmentof high fevers ulcers inflammation and even cancer Themain bioactive flavonoids in Scutellaria baicalensis includebaicalein baicalin (BA) (baicalein-7-glucuronide) wogoninwogonoside (wogonin-7-glucuronide) oroxylin A and orox-ylin A-7-glucuronide Scutellaria baicalensis and its flavoneshave been studied for their various pharmacological activi-ties including anti-inflammatory [28] antibacterial [29]neuroprotective [30] anticonvulsant [31] antiviral [32]antitumor [33] and antioxidant [34] activities BA is themostpopular bioactive flavonoid for treating ulcers However the
(a) (b) (c)
(d) (e) (f)
(g) (h)
Figure 3 Photomicrographs of acetic acid-induced gastric ulcers from different groups (a) sham group (b) HE staining of the model groupinduced by acetic acid (cndashe) HE staining of the BA-Zn group induced by acetic acid and treated daily with BA-Zn (325 65 and 13mgkgpo) (f) HE staining of the BA group induced by acetic acid and treated daily with BA (46mgkg po) (g) HE staining of the zinc-gluconategroup induced by acetic acid and treated daily with zinc-gluconate (932mgkg po) and (h) HE staining of the omeprazole group inducedby acetic acid and treated daily with omeprazole (40mgkg po) The HE stained slides were visualized under a bright field microscopewith 20x magnification
Table 2 Concentration of TNF-α and IL-8 in rat mucosa inducedby acetic acid
Omeprazole 4 132plusmn 009lowastlowastlowast 045plusmn 001lowastlowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
6 Gastroenterology Research and Practice
antichronic gastric ulcer effects of BA alone or in complexhave not yet been elucidated
In this paper we examined the effects of BA-Zn BA andzinc-gluconate and related mechanisms on gastric ulcer heal-ing in an acetic acid-induced gastric ulcer rat model It hasbeen reported that zinc-gluconate has a protective effect ongastric ulcers [35] Acetic acid induces a state of acute stressin the gastric mucosa subsequently inducing gastric ulcersMoreover acetic acid-induced gastric ulceration leads tochronic oxidative stress with decreased SOD activity andGSH-Px expression levels and increased lipid peroxidation(MDA) It is well known that SOD GSH-Px and MDA playimportant roles in protecting the gastric mucosa against var-ious damaging agents [36 37] GSH-Px also plays an impor-tant role in protecting against oxidative gastric mucosalinjury [38] MDA is currently regarded as a reliable indexof ROS-induced mucosal injury [39] Therefore the detec-tion of SOD GSH-Px and MDA contents can reflect andindicate the level of oxidative stress In addition increasedconcentrations of TNF-α and IL-8 were detected in the ulcer-ated gastric mucosa BA-Zn (13mgkg) significantly acceler-ated the healing of gastric ulcers through an increase in SODand GSH-Px activity and a decrease in MDA IL-8 and TNF-α contents We also detected the levels of SOD IL-8 andTNF-α by Western blot We found that BA-Zn significantlyaccelerated ulcer healing by decreasing oxidative stress andattenuating inflammation In our results zinc-gluconate alsohas a protective effect on gastric ulcers but BA-Zn has much
stronger protective and healing abilities in gastric ulcers Onthe basis of our data BA-Zn (13mgkg) has greater antigas-tric ulcer abilities than either BA or zinc-gluconate
Collectively BA-Zn presents important ulcer-healingproperties in the model of chronic ulcer induced by aceticacid in rats Omeprazole is one of the most popular drugsused for the therapeutic control of gastroduodenal ulcers inhumans In our work BA-Zn also exerted an antiulcerogeniceffect similar to that of omeprazole against the developmentof acetic acid-induced gastric ulcers in rats using antioxidantand anti-inflammatory abilities Therefore the BA-Zn com-plex may become a potential and promising drug for thetreatment of human gastroduodenal ulcers In summaryour study indicates that BA-Zn promotes ulcer healing bydecreasing oxidative stress and attenuating inflammation inan acetic acid-induced gastric ulcer rat model Howeveradditional studies are needed to explore the novel mecha-nisms of BA-Zn and determine whether other mechanismsare also involved in the antiulcer effects of this complex
5 Conclusion
In conclusion BA-Zn facilitates the healing of acetic-inducedchronic ulcers in rats through its antioxidant and anti-inflammatory properties The results of this study provide afoundation for the clinical application of BA-Zn in the treat-ment of gastroduodenal ulcers
SOD
IL-8
TNF-훼
훽-Actin
Sham Model BA O325
BA-Zn (mgkg)
Z1365
(a)
SOD25
2015100500
Sham
Mod
el BA 325 6
5
BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Sham
Mod
el BA 325 6
5BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Sham
Mod
el BA 325 6
5
BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Prot
ein
leve
l
20
15
10
05
00
Prot
ein
leve
l20
15
10
05
00
Prot
ein
leve
l
IL-8 TNF-훼
(b)
Figure 4 Western blot analysis of SOD TNF-α and IL-8 expression (a) The protein expression levels of SOD TNF-α and IL-8 wereanalyzed by Western blot analysis β-Actin was used as a loading control (b) Quantification of SOD TNF-α and IL-8 protein expressionlevels using ImageJ software Z zinc-gluconate O omeprazole lowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
7Gastroenterology Research and Practice
Data Availability
The data used to support the findings of this study are avail-able from the corresponding author upon request
Conflicts of Interest
The authors declare that there are no conflicts of interest andno financial conflicts regarding the publication of this paper
Authorsrsquo Contributions
This study was designed by Xu Liu Experimental work wasdone by Hui Yang Zhong-Kun Ren Yi Lu Xiao-Feng Zengand Ling Li The first draft of this paper was written by HuiYang and reviewed by Xu Liu and Rong-Ping ZhangZhong-Kun Ren and Yi Lu reviewed the methodology andresults All authors reviewed and approved the final version
Acknowledgments
The present study was supported by the Yunnan AppliedBasic Research Projects (Grant no 2005C00092)
References
[1] J L Goldstein J Aisenberg F Lanza et al ldquoA multicenterrandomized double-blind active-comparator placebo-con-trolled parallel-group comparison of the incidence of endo-scopic gastric and duodenal ulcer rates with valdecoxib ornaproxen in healthy subjects aged 65 to 75 yearsrdquo ClinicalTherapeutics vol 28 no 3 pp 340ndash351 2006
[2] G H Heeba M K A Hassan and R S Amin ldquoGastroprotec-tive effect of simvastatin against indomethacin-induced gastriculcer in rats role of nitric oxide and prostaglandinsrdquo EuropeanJournal of Pharmacology vol 607 no 1ndash3 pp 188ndash193 2009
[3] P A Gladding M W I Webster H B Farrell I S L ZengR Park and N Ruijne ldquoThe antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacody-namic interaction with aspirin in healthy volunteersrdquo TheAmerican Journal of Cardiology vol 101 no 7 pp 1060ndash1063 2008
[4] A Lanas M A Perez-Aisa F Feu et al ldquoA nationwide studyof mortality associated with hospital admission due to severegastrointestinal events and those associated with nonsteroidalantiinflammatory drug userdquo The American Journal of Gastro-enterology vol 100 no 8 pp 1685ndash1693 2005
[5] B Cryer and K W Mahaffey ldquoGastrointestinal ulcers role ofaspirin and clinical outcomes pathobiology diagnosis andtreatmentrdquo Journal of Multidisciplinary Healthcare vol 7pp 137ndash146 2014
[6] J Lu J S Wang and L Y Kong ldquoAnti-inflammatory effects ofHuang-Lian-Jie-Du decoction its two fractions and four typi-cal compoundsrdquo Journal of Ethnopharmacology vol 134no 3 pp 911ndash918 2011
[7] J M Hwang T H Tseng Y Y Tsai et al ldquoProtective effects ofbaicalein on tert-butyl hydroperoxide-induced hepatic toxicityin rat hepatocytesrdquo Journal of Biomedical Science vol 12no 2 pp 389ndash397 2005
[8] J Dou L Chen G Xu et al ldquoEffects of baicalein on Sendaivirus in vivo are linked to serum baicalin and its inhibition
of hemagglutinin-neuraminidaserdquo Archives of Virologyvol 156 no 5 pp 793ndash801 2011
[9] M Y Yun J H Yang D K Kim et al ldquoTherapeutic effects ofbaicalein on atopic dermatitis-like skin lesions of NCNgamice induced by Dermatophagoides pteronyssinusrdquo Interna-tional Immunopharmacology vol 10 no 9 pp 1142ndash11482010
[10] J H Liu H Wann M M Chen et al ldquoBaicalein signifi-cantly protects human retinal pigment epithelium cellsagainst H2O2-induced oxidative stress by scavenging reac-tive oxygen species and downregulating the expression ofmatrix metalloproteinase-9 and vascular endothelial growthfactorrdquo Journal of Ocular Pharmacology and Therapeuticsvol 26 no 5 pp 421ndash429 2010
[11] P D Zalewski A Q Truong-Tran D Grosser L JayaramC Murgia and R E Ruffin ldquoZinc metabolism in airway epi-thelium and airway inflammation basic mechanisms and clin-ical targets A reviewrdquo Pharmacology amp Therapeutics vol 105no 2 pp 127ndash149 2005
[12] M Odashima M Otaka M Jin et al ldquoZinc L-carnosine pro-tects colonic mucosal injury through induction of heat shockprotein 72 and suppression of NF-κB activationrdquo Life Sciencesvol 79 no 24 pp 2245ndash2250 2006
[13] A Bhattacharyya R Chattopadhyay S Mitra and S E CroweldquoOxidative stress an essential factor in the pathogenesis of gas-trointestinal mucosal diseasesrdquo Physiological Reviews vol 94no 2 pp 329ndash354 2014
[14] L Chanudom and J Tangpong ldquoAnti-inflammation propertyof Syzygium cumini (L) Skeels on indomethacin-inducedacute gastric ulcerationrdquo Gastroenterology Research and Prac-tice vol 2015 Article ID 343642 12 pages 2015
[15] L M da Silva A Allemand D A G B Mendes et al ldquoEtha-nolic extract of roots from Arctium lappa L accelerates thehealing of acetic acid-induced gastric ulcer in rats involve-ment of the antioxidant systemrdquo Food and Chemical Toxicol-ogy vol 51 pp 179ndash187 2013
[16] S K Jaiswal C V Rao B Sharma P Mishra S Das andM KDubey ldquoGastroprotective effect of standardized leaf extractfrom Argyreia speciosa on experimental gastric ulcers in ratsrdquoJournal of Ethnopharmacology vol 137 no 1 pp 341ndash3442011
[17] A A El-Fakhry M A El-Daker R I Badr et al ldquoAssociationof the CagA gene positive Helicobacter pylori and tissue levelsof interleukin-17 and interleukin-8 in gastric ulcer patientsrdquoThe Egyptian Journal of Immunology vol 19 no 1 pp 51ndash62 2012
[18] Y W Yin A M Hu Q Q Sun et al ldquoAssociation betweeninterleukin-8 gene minus251 TA polymorphism and the risk ofpeptic ulcer disease a meta-analysisrdquo Human Immunologyvol 74 no 1 pp 125ndash130 2013
[19] S Okabe J L A Roth and C J Pfeiffer ldquoA method for exper-imental penetrating gastric and duodenal ulcers in ratsObservations on normal healingrdquo The American Journal ofDigestive Diseases vol 16 no 3 pp 277ndash284 1971
[20] K Takagi S Okabe and R Saziki ldquoA newmethod for the pro-duction of chronic gastric ulcer in rats and the effect of severaldrugs on its healingrdquo Japanese Journal of Pharmacologyvol 19 no 3 pp 418ndash426 1969
[21] S Okabe and K Amagase ldquoAn overview of acetic acid ulcermodelsmdashthe history and state of the art of peptic ulcerresearchrdquo Biological amp Pharmaceutical Bulletin vol 28no 8 pp 1321ndash1341 2005
8 Gastroenterology Research and Practice
[22] A Tarnawski J Stachura W J Krause T G Douglass andH Gergely ldquoQuality of gastric ulcer healing a new emerg-ing conceptrdquo Journal of Clinical Gastroenterology vol 13Supplement 1 pp S42ndashS47 1991
[23] A S Tarnawski ldquoCellular and molecular mechanisms of gas-trointestinal ulcer healingrdquo Digestive Diseases and Sciencesvol 50 Supplement 1 pp S24ndashS33 2005
[24] M Arun and V V Asha ldquoGastroprotective effect of Dodonaeaviscosa on various experimental ulcer modelsrdquo Journal of Eth-nopharmacology vol 118 no 3 pp 460ndash465 2008
[25] A Alkofahi and A H Atta ldquoPharmacological screening of theanti-ulcerogenic effects of some Jordanian medicinal plants inratsrdquo Journal of Ethnopharmacology vol 67 no 3 pp 341ndash345 1999
[26] S Khennouf H Benabdallah K Gharzouli et al ldquoEffect oftannins from Quercus suber and Quercus coccifera leaves onethanol-induced gastric lesions in micerdquo Journal of Agricul-tural and Food Chemistry vol 51 no 5 pp 1469ndash1473 2003
[27] S Bhattacharya S R Chaudhuri S Chattopadhyay and S KBandyopadhyay ldquoHealing properties of some Indian medici-nal plants against indomethacin-induced gastric ulceration ofratsrdquo Journal of Clinical Biochemistry and Nutrition vol 41no 2 pp 106ndash114 2007
[28] B Q Li T Fu W H Gong et al ldquoThe flavonoid baicalinexhibits anti-inflammatory activity by binding to chemo-kinesrdquo Immunopharmacology vol 49 no 3 pp 295ndash3062000
[29] J Wu D Hu and K X Wang ldquoStudy of Scutellaria baicalensisand Baicalin against antimicrobial susceptibility of Helicobac-ter pylori strains in vitrordquo Zhong yao cai = Zhongyaocai = Jour-nal of Chinese Medicinal Materials vol 31 no 5 pp 707ndash7102008
[30] A M Y Lin Y H Ping G F Chang et al ldquoNeuroprotectiveeffect of oral SB remedy (Scutellaria baicalensis Georgi andBupleurum scorzonerifolfium Willd) on iron-induced neuro-degeneration in the nigrostriatal dopaminergic system of ratbrainrdquo Journal of Ethnopharmacology vol 134 no 3pp 884ndash891 2011
[31] S Y Yoon I C dela Pena C Y Shin et al ldquoConvulsion-related activities of Scutellaria flavones are related to the 57-dihydroxyl structuresrdquo European Journal of Pharmacologyvol 659 no 2-3 pp 155ndash160 2011
[32] L Chen J Dou Z Su et al ldquoSynergistic activity of baicaleinwith ribavirin against influenza A (H1N1) virus infections incell culture and in micerdquo Antiviral Research vol 91 no 3pp 314ndash320 2011
[33] M Li-Weber ldquoNew therapeutic aspects of flavones the anti-cancer properties of Scutellaria and its main active constitu-ents wogonin baicalein and baicalinrdquo Cancer TreatmentReviews vol 35 no 1 pp 57ndash68 2009
[34] D E Shieh L T Liu and C C Lin ldquoAntioxidant and free rad-ical scavenging effects of baicalein baicalin and wogoninrdquoAnticancer Research vol 20 no 5A pp 2861ndash2865 2000
[35] B Bandyopadhyay and S K Bandyopadhyay ldquoProtectiveeffect of zinc gluconate on chemically induced gastric ulcerrdquoThe Indian Journal of Medical Research vol 106 pp 27ndash321997
[36] S S Poulsen ldquoOn the role of epidermal growth factor in thedefence of the gastroduodenal mucosardquo Scandinavian Journalof Gastroenterology vol 128 pp 20ndash23 1987
[37] S Kwiecień T Brzozowski P C H Konturek and S JKonturek ldquoThe role of reactive oxygen species in action ofnitric oxide-donors on stress-induced gastric mucosal lesionsrdquoJournal of Physiology and Pharmacology vol 53 4 Part 2pp 761ndash773 2002
[38] I Chattopadhyay U Bandyopadhyay K Biswas P Maity andR K Banerjee ldquoIndomethacin inactivates gastric peroxidase toinduce reactive-oxygen-mediated gastric mucosal injury andcurcumin protects it by preventing peroxidase inactivationand scavenging reactive oxygenrdquo Free Radical Biology amp Med-icine vol 40 no 8 pp 1397ndash1408 2006
[39] M Maes P Ruckoanich Y S Chang N Mahanonda andM Berk ldquoMultiple aberrations in shared inflammatory andoxidative amp nitrosative stress (IOampNS) pathways explain theco-association of depression and cardiovascular disorder(CVD) and the increased risk for CVD and due mortality indepressed patientsrdquo Progress in Neuro-Psychopharmacologyand Biological Psychiatry vol 35 no 3 pp 769ndash783 2011
Computational and Mathematical Methods in Medicine
Hindawiwwwhindawicom Volume 2018
Behavioural Neurology
OphthalmologyJournal of
Hindawiwwwhindawicom Volume 2018
Diabetes ResearchJournal of
Hindawiwwwhindawicom Volume 2018
Hindawiwwwhindawicom Volume 2018
Research and TreatmentAIDS
Hindawiwwwhindawicom Volume 2018
Gastroenterology Research and Practice
Hindawiwwwhindawicom Volume 2018
Parkinsonrsquos Disease
Evidence-Based Complementary andAlternative Medicine
Volume 2018Hindawiwwwhindawicom
Submit your manuscripts atwwwhindawicom
absorbance were determined using a spectrophotometer theresults are expressed as Ul and μmoll for GSH-Px andMDA Umg protein for SOD activity and ngml for IL-8and TNF-α levels
28 Western Blot Analysis Western blot analysis was usedfor the protein expression levels of SOD1 TNF-α andIL-8 Total proteins of tissues were extracted with lysisbuffer (Beyotime China) The insoluble protein lysate wasremoved by centrifugation at 10000timesg for 10min at 4degCTotal proteins were separated by 10 sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE)followed by blocking in 5 skim milk on a PVDF mem-brane The membranes were hybridized with primary anti-bodies (Proteintech USA) for 2 h at 4degC and then withsecondary antibodies (Proteintech USA) for 2 h at roomtemperature The bands were developed using an enhancedchemiluminescence (ECL) detection system (EMDMilliporeUSA) for horseradish peroxidase (HRP) The relativeamounts of the various proteins were analyzed β-Actin wasused as a loading control The results were quantified usingImageJ software
29 Statistical Analysis All the results were expressed asmeanplusmn SD Statistical comparisons were made betweendrug-treated groups and acetic acid groups The data was sta-tistically analyzed by one-way analysis of variance (ANOVA)(Tukeyrsquos post hoc test) using GraphPad Prism softwareversion 50a (GraphPad Software Inc California USA)P lt 0 05 was considered to be statistically significant
3 Results
31 BA-Zn Protects against Acetic Acid-Induced GastricLesions The molecular formula of BA-Zn isZn(C21H17O11)(CH3COO)sdot35H2O and it has a molecularweight of 632 gmol (Figure 1) The macroscopic appearanceof the gastric tissue is shown in Figure 2 Rats treated withonly water (Figure 2(a)) showed a normal glandular stomachFigure 2(b) shows the deep ulceration and severe edematouschanges in the gastric mucosa of the model group that wasinduced with 80 acetic acid and treated with water dailyBy contrast rats treated with BA-Zn (325 65 or 13mg
kg) or BA zinc-gluconate or omeprazole showed less severeulceration and less edema in the gastric mucosa induced by80 acetic acid (Figures 2(c)ndash2(h))
As shown in Figure 3(a) the microscopic histologicalappearance of the gastric tissue and the normal gastric epi-thelium was observed in the sham group The applicationof acetic acid induced the disruption of the superficial regionof the gastric gland with loss of epithelial cells as well as pro-nounced edema of the submucosa and degradation of themucosa in the model group (Figure 3(b))
BA-Zn (325 65 and 13mgkg) and omeprazole mark-edly reduced the severity of gastric ulcers (swelling destruc-tion and extensive destruction on the surface of theepithelium) and promoted marginal regeneration of the epi-thelium compared to the model group (Figures 3(c)ndash3(e) and3(h)) In the BA (46mgkg) and zinc-gluconate- (932mgkg) treated groups the severity of the gastric ulcers was alsoinhibited (Figures 3(f) and 3(g))
In all animals from all the groups that survived the lon-gitudinal and abscissal lengths of the upper opened part ofthe ulcer were measured with a micrometer that wasattached to a stereoscopic microscope and the product ofboth lengths (mm2) was expressed in terms of the ulcerindex As shown in Table 1 the sham group showed noulcer index and administration of BA-Zn at doses of 32565 and 13mgkg decreased the gastric ulcer index to2494plusmn 200 (P lt 0 05) 1843plusmn 111 (P lt 0 001) and 1500plusmn144mm2 (P lt 0 001) (120 350 and 471 protectionrespectively) compared to the ulcer index of the model groupwhich was 2835plusmn 327mm2 BA (46mgkg) reduced thegastric ulcer index to 2438plusmn 230 (P lt 0 05) compared tothat of the model group Zinc-gluconate (932mgkg) alsoreduced the gastric ulcer index to 2371plusmn 200 (P lt 0 05)compared to that of the model group Moreover zinc-gluconate had a higher gastric ulcer index than the BA-Zngroup (65 and 13mgkg P lt 0 001 respectively) It indicatedthat BA-Zn (65 and 13mgkg) has a stronger healing effectthan zinc-gluconate Omeprazole (40mgkg) the positivecontrol drug demonstrated a potency for reducing the gas-tric ulcer index (1535plusmn 122mm2 P lt 0 001 compared tothe model group) BA-Zn (13mgkg) showed the bestpotency for reducing the gastric ulcer index which was thesame as omeprazole
Table 1 Effect of BA-Zn on oxidant stress in rat mucosa induced by acetic acid
Group (mgkg) Ulcer index (mm2) SOD (Umg) MDA (μmoll) GSH-Px (Ul)
Omeprazole 4 1535plusmn 122lowastlowastlowast 1932plusmn 009lowastlowastlowast 100plusmn 011lowastlowastlowast 10712plusmn 905lowastlowastlowastlowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
3Gastroenterology Research and Practice
32 BA-Zn Suppressed Oxidative Stress in Acetic Acid-Induced Gastric Tissue of Rats Increased oxidative stresswas shown in the ulcerated gastric mucosa of the modelgroup and this group also had significantly decreased SODand GSH-Px activities and an increased level of lipid peroxi-dation (MDA) content compared to those of the sham group(P lt 0 001)
As shown in Table 1 SOD activity in the mucosa of themodel group was significantly lower (703plusmn 010Umg pro-tein) than in the sham group (2209plusmn 009Umg proteinP lt 0 001) BA-Zn treatment at 65 and 13mgkg significantlyincreased the SOD activity to 1762plusmn 011 and 2012plusmn 032Umg protein (P lt 0 001 and P lt 0 001) respectively comparedto that of the model group (703plusmn 010Umg protein) More-over the administration of 65 and 13mgkg BA-Zn led tohigher SOD activity than did the administration of BA(1762plusmn 011 and 2012plusmn 032 vs 1209plusmn 013Umg proteinP lt 0 05 and P lt 0 01) and these also markedly increasedSOD activity than that of the zinc-gluconate group (907plusmn033Umg protein P lt 0 001) It indicated that BA-Zn hasa stronger antioxidative effect than BA and zinc-gluconateZinc-gluconate (932mgkg) significantly increased SODactivity to 907plusmn 033Umg protein (P lt 0 05) compared tothat of the model group (703plusmn 010Umg protein) Omep-razole (40mgkg) demonstrated an increase in SOD activity(1932plusmn 009Umg protein P lt 0 001 compared to that ofthe model group)
GSH-Px levels in the gastric mucosa of the model groupwere significantly lower than in the sham group (5221plusmn713 vs 13609plusmn 909Ul P lt 0 001) Administration of 65and 13mgkg BA-Zn significantly increased the GSH-Pxlevel in a dose-dependent manner (P lt 0 001 and P lt 0 001respectively compared to that of the model group) More-over the administration of 65 and 13mgkg BA-Zn led toincreased GSH-Px activity compared to that of the BA group(10212plusmn 911 and12025plusmn 907 vs 8507plusmn 711UlP lt 0 05)and the administration of 65 and 13mgkg BA-Zn alsomarkedly increased GSH-Px activity compared to that ofthe zinc-gluconate group (8035plusmn 677Ul P lt 0 001) Itindicated that BA-Zn has a stronger antioxidative effectthan BA and zinc-gluconate Zinc-gluconate (932mgkg)
significantly increased GSH-Px activity to 8035plusmn 677Ul(P lt 0 05) compared to that of the model group (5221plusmn713Ul) Omeprazole (40mgkg) demonstrated an increasein GSH-Px activity (10712plusmn 905Ul P lt 0 001 comparedto that of the model group)
The inhibitory effects of BA-Zn on lipid peroxidation(MDA) are shown in Table 1 The MDA content in thegastric mucosa of the model group was higher than in thesham group (239plusmn 003 vs 091plusmn 006μmoll P lt 0 001)Treatment with 325 65 and 13mgkg BA-Zn significantlydecreased the MDA content to 175plusmn 007 133plusmn 007 and063plusmn 001μmoll (P lt 0 01 P lt 0 001 and P lt 0 001respectively compared to that of the model group) More-over the administration of 325 65 and 13mgkg BA-Znled to lower MDA activity than BA (175plusmn 007 133plusmn007 and 063plusmn 901 vs 354plusmn 004μmoll P lt 0 05) andthe zinc-gluconate group (200plusmn 012μmoll P lt 0 001)indicating that BA-Zn had a stronger antioxidative effectthan BA and zinc-gluconate Zinc-gluconate (932mgkg)showed a decrease in MDA content (200plusmn 012μmollP lt 0 05 compared to that the model group) Omeprazole(40mgkg) also demonstrated a decrease in MDA con-tent (100plusmn 011μmoll P lt 0 001 compared to that of themodel group)
33 Effect of BA-Zn on the Concentration of TNF-α and IL-8As shown in Table 2 the level of TNF-α in the model groupwas significantly higher than in the sham group (273plusmn 010vs 072plusmn 009 ngml P lt 0 001) The administration of 32565 and 13mgkg BA-Zn significantly decreased the TNF-αconcentration in a dose-dependent manner (195plusmn 006162plusmn 011 and 112plusmn 032 P lt 0 05 P lt 0 001 and P lt0 001 respectively compared to that of the model group)Zinc-gluconate (932mgkg) demonstrated a decreased TNF-α level (200plusmn011ngml P lt 0 05 compared to that of themodel group) Administration of 65 and 13mgkg BA-Zn sig-nificantly decreased the TNF-α concentration compared to thatof the zinc-gluconate group (200plusmn011ngml P lt 0 001)Omeprazole (40mgkg) demonstrated a decreased TNF-αconcentration (132plusmn 009 ngml P lt 0 001 compared to thatof the model group)
CH3
O
OO
O
OO
O
35H2OOH
OH
OH
OH
HO
OZn
Figure 1 Structural formula of BA-Zn
4 Gastroenterology Research and Practice
The level of IL-8 in the model group was significantlyhigher than in the sham group (069plusmn 003 vs 021plusmn006 ngml P lt 0 01) Administration of 325 65 and13mgkg BA-Zn significantly decreased the IL-8 level in adose-dependent manner (036plusmn 007 033plusmn 007 and 029plusmn001 P lt 0 01 P lt 0 01 and P lt 0 001 respectively com-pared to that of the model group) Zinc-gluconate (932mgkg) demonstrated a decreased IL-8 level (060plusmn 001 ngmlP lt 0 05 compared to that of the model group) Administra-tion of 325 65 and 13mgkg BA-Zn significantly decreasedthe IL-8 concentration compared to that of the zinc-gluconate group (060plusmn 001 ngml P lt 0 001) Omeprazole(40mgkg) also demonstrated a decreased IL-8 level (045plusmn001 ngml P lt 0 05 compared to the model group)
To further demonstrate the effect of BA-Zn on the con-centration of SOD TNF-α and IL-8 in the above groupsWestern blot assays were used to detect the expression levelsof these proteins In Figure 4(a) and 4(b) we reveal thatBA-Zn treatment significantly increased SOD expression
compared to that in the model and zinc-gluconate groupsBA-Zn also significantly decreased the expression of TNF-αand IL-8 compared to that in the model and zinc-gluconategroups In summary the above results indicate that BA-Znhad better antioxidative and anti-inflammatory effects thanboth BA and zinc-gluconate
4 Discussion
Gastric ulcer is a common dysfunction of the digestive sys-tem and an increasing number of people worldwide are suf-fering damage from ulcers The acetic acid-induced ulcermodel resembles human chronic ulcers in both pathologicalfeatures and aspects of the healing process [20 21] thus itis themostusefulmodel forus tousewhen investigating gastriculcers Previous studies have demonstrated that experimentalgastric ulcers have many histological and ultrastructuralabnormalities including a reduced height marked dilationof gastric glands and increased connective tissue that may
(a) (b) (c)
(d) (e) (f)
(g) (h)
Figure 2 Appearances of acetic acid-induced gastric ulcers in different groups (a) the sham group treated daily with water (b) an ulcerationfrom the model group induced by acetic acid (cndashe) an ulceration from the BA-Zn group induced by acetic acid and treated daily with BA-Zn(325 65 and 13mgkg po) (f) an ulceration from the BA group induced by acetic acid and treated daily with BA (46mgkg po) (g) anulceration from the zinc-gluconate group induced by acetic acid and treated daily with zinc-gluconate (932mgkg po) and (h) an ulcerationfrom the omeprazole group induced by acetic acid and treated daily with omeprazole (40mgkg po) Black arrows indicate ulcer location
5Gastroenterology Research and Practice
interfere with the mucosal defense system and cause ulcerrecurrence with some ulcerogenic factors [22 23]
In recent years chemical drugs used for the treatmentof gastric ulcers have induced many side effects Recentlynewly developed drugs with herbal origins may offerreduced side effects compared with chemical drugs [24]
In folk knowledge medicinal plants have been used forthe treatment of various disorders More and more medic-inal plants with various therapeutic properties especially forthe treatment of gastritis and gastric ulcers have been identi-fied [25ndash27] However few traditional Chinese medicinalplants for gastric ulcer treatment have been studied Cur-rently because of the lack of effective and applicable pharma-cological treatments for gastric ulcer more and more peoplehave focused on traditional medicines The investigation ofthe therapeutic functions of traditional medicinal herbs ingastric ulcer offer promising potential
Scutellaria baicalensis is a popular medicinal herb used intraditional Chinese medicine and it is used for the treatmentof high fevers ulcers inflammation and even cancer Themain bioactive flavonoids in Scutellaria baicalensis includebaicalein baicalin (BA) (baicalein-7-glucuronide) wogoninwogonoside (wogonin-7-glucuronide) oroxylin A and orox-ylin A-7-glucuronide Scutellaria baicalensis and its flavoneshave been studied for their various pharmacological activi-ties including anti-inflammatory [28] antibacterial [29]neuroprotective [30] anticonvulsant [31] antiviral [32]antitumor [33] and antioxidant [34] activities BA is themostpopular bioactive flavonoid for treating ulcers However the
(a) (b) (c)
(d) (e) (f)
(g) (h)
Figure 3 Photomicrographs of acetic acid-induced gastric ulcers from different groups (a) sham group (b) HE staining of the model groupinduced by acetic acid (cndashe) HE staining of the BA-Zn group induced by acetic acid and treated daily with BA-Zn (325 65 and 13mgkgpo) (f) HE staining of the BA group induced by acetic acid and treated daily with BA (46mgkg po) (g) HE staining of the zinc-gluconategroup induced by acetic acid and treated daily with zinc-gluconate (932mgkg po) and (h) HE staining of the omeprazole group inducedby acetic acid and treated daily with omeprazole (40mgkg po) The HE stained slides were visualized under a bright field microscopewith 20x magnification
Table 2 Concentration of TNF-α and IL-8 in rat mucosa inducedby acetic acid
Omeprazole 4 132plusmn 009lowastlowastlowast 045plusmn 001lowastlowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
6 Gastroenterology Research and Practice
antichronic gastric ulcer effects of BA alone or in complexhave not yet been elucidated
In this paper we examined the effects of BA-Zn BA andzinc-gluconate and related mechanisms on gastric ulcer heal-ing in an acetic acid-induced gastric ulcer rat model It hasbeen reported that zinc-gluconate has a protective effect ongastric ulcers [35] Acetic acid induces a state of acute stressin the gastric mucosa subsequently inducing gastric ulcersMoreover acetic acid-induced gastric ulceration leads tochronic oxidative stress with decreased SOD activity andGSH-Px expression levels and increased lipid peroxidation(MDA) It is well known that SOD GSH-Px and MDA playimportant roles in protecting the gastric mucosa against var-ious damaging agents [36 37] GSH-Px also plays an impor-tant role in protecting against oxidative gastric mucosalinjury [38] MDA is currently regarded as a reliable indexof ROS-induced mucosal injury [39] Therefore the detec-tion of SOD GSH-Px and MDA contents can reflect andindicate the level of oxidative stress In addition increasedconcentrations of TNF-α and IL-8 were detected in the ulcer-ated gastric mucosa BA-Zn (13mgkg) significantly acceler-ated the healing of gastric ulcers through an increase in SODand GSH-Px activity and a decrease in MDA IL-8 and TNF-α contents We also detected the levels of SOD IL-8 andTNF-α by Western blot We found that BA-Zn significantlyaccelerated ulcer healing by decreasing oxidative stress andattenuating inflammation In our results zinc-gluconate alsohas a protective effect on gastric ulcers but BA-Zn has much
stronger protective and healing abilities in gastric ulcers Onthe basis of our data BA-Zn (13mgkg) has greater antigas-tric ulcer abilities than either BA or zinc-gluconate
Collectively BA-Zn presents important ulcer-healingproperties in the model of chronic ulcer induced by aceticacid in rats Omeprazole is one of the most popular drugsused for the therapeutic control of gastroduodenal ulcers inhumans In our work BA-Zn also exerted an antiulcerogeniceffect similar to that of omeprazole against the developmentof acetic acid-induced gastric ulcers in rats using antioxidantand anti-inflammatory abilities Therefore the BA-Zn com-plex may become a potential and promising drug for thetreatment of human gastroduodenal ulcers In summaryour study indicates that BA-Zn promotes ulcer healing bydecreasing oxidative stress and attenuating inflammation inan acetic acid-induced gastric ulcer rat model Howeveradditional studies are needed to explore the novel mecha-nisms of BA-Zn and determine whether other mechanismsare also involved in the antiulcer effects of this complex
5 Conclusion
In conclusion BA-Zn facilitates the healing of acetic-inducedchronic ulcers in rats through its antioxidant and anti-inflammatory properties The results of this study provide afoundation for the clinical application of BA-Zn in the treat-ment of gastroduodenal ulcers
SOD
IL-8
TNF-훼
훽-Actin
Sham Model BA O325
BA-Zn (mgkg)
Z1365
(a)
SOD25
2015100500
Sham
Mod
el BA 325 6
5
BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Sham
Mod
el BA 325 6
5BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Sham
Mod
el BA 325 6
5
BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Prot
ein
leve
l
20
15
10
05
00
Prot
ein
leve
l20
15
10
05
00
Prot
ein
leve
l
IL-8 TNF-훼
(b)
Figure 4 Western blot analysis of SOD TNF-α and IL-8 expression (a) The protein expression levels of SOD TNF-α and IL-8 wereanalyzed by Western blot analysis β-Actin was used as a loading control (b) Quantification of SOD TNF-α and IL-8 protein expressionlevels using ImageJ software Z zinc-gluconate O omeprazole lowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
7Gastroenterology Research and Practice
Data Availability
The data used to support the findings of this study are avail-able from the corresponding author upon request
Conflicts of Interest
The authors declare that there are no conflicts of interest andno financial conflicts regarding the publication of this paper
Authorsrsquo Contributions
This study was designed by Xu Liu Experimental work wasdone by Hui Yang Zhong-Kun Ren Yi Lu Xiao-Feng Zengand Ling Li The first draft of this paper was written by HuiYang and reviewed by Xu Liu and Rong-Ping ZhangZhong-Kun Ren and Yi Lu reviewed the methodology andresults All authors reviewed and approved the final version
Acknowledgments
The present study was supported by the Yunnan AppliedBasic Research Projects (Grant no 2005C00092)
References
[1] J L Goldstein J Aisenberg F Lanza et al ldquoA multicenterrandomized double-blind active-comparator placebo-con-trolled parallel-group comparison of the incidence of endo-scopic gastric and duodenal ulcer rates with valdecoxib ornaproxen in healthy subjects aged 65 to 75 yearsrdquo ClinicalTherapeutics vol 28 no 3 pp 340ndash351 2006
[2] G H Heeba M K A Hassan and R S Amin ldquoGastroprotec-tive effect of simvastatin against indomethacin-induced gastriculcer in rats role of nitric oxide and prostaglandinsrdquo EuropeanJournal of Pharmacology vol 607 no 1ndash3 pp 188ndash193 2009
[3] P A Gladding M W I Webster H B Farrell I S L ZengR Park and N Ruijne ldquoThe antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacody-namic interaction with aspirin in healthy volunteersrdquo TheAmerican Journal of Cardiology vol 101 no 7 pp 1060ndash1063 2008
[4] A Lanas M A Perez-Aisa F Feu et al ldquoA nationwide studyof mortality associated with hospital admission due to severegastrointestinal events and those associated with nonsteroidalantiinflammatory drug userdquo The American Journal of Gastro-enterology vol 100 no 8 pp 1685ndash1693 2005
[5] B Cryer and K W Mahaffey ldquoGastrointestinal ulcers role ofaspirin and clinical outcomes pathobiology diagnosis andtreatmentrdquo Journal of Multidisciplinary Healthcare vol 7pp 137ndash146 2014
[6] J Lu J S Wang and L Y Kong ldquoAnti-inflammatory effects ofHuang-Lian-Jie-Du decoction its two fractions and four typi-cal compoundsrdquo Journal of Ethnopharmacology vol 134no 3 pp 911ndash918 2011
[7] J M Hwang T H Tseng Y Y Tsai et al ldquoProtective effects ofbaicalein on tert-butyl hydroperoxide-induced hepatic toxicityin rat hepatocytesrdquo Journal of Biomedical Science vol 12no 2 pp 389ndash397 2005
[8] J Dou L Chen G Xu et al ldquoEffects of baicalein on Sendaivirus in vivo are linked to serum baicalin and its inhibition
of hemagglutinin-neuraminidaserdquo Archives of Virologyvol 156 no 5 pp 793ndash801 2011
[9] M Y Yun J H Yang D K Kim et al ldquoTherapeutic effects ofbaicalein on atopic dermatitis-like skin lesions of NCNgamice induced by Dermatophagoides pteronyssinusrdquo Interna-tional Immunopharmacology vol 10 no 9 pp 1142ndash11482010
[10] J H Liu H Wann M M Chen et al ldquoBaicalein signifi-cantly protects human retinal pigment epithelium cellsagainst H2O2-induced oxidative stress by scavenging reac-tive oxygen species and downregulating the expression ofmatrix metalloproteinase-9 and vascular endothelial growthfactorrdquo Journal of Ocular Pharmacology and Therapeuticsvol 26 no 5 pp 421ndash429 2010
[11] P D Zalewski A Q Truong-Tran D Grosser L JayaramC Murgia and R E Ruffin ldquoZinc metabolism in airway epi-thelium and airway inflammation basic mechanisms and clin-ical targets A reviewrdquo Pharmacology amp Therapeutics vol 105no 2 pp 127ndash149 2005
[12] M Odashima M Otaka M Jin et al ldquoZinc L-carnosine pro-tects colonic mucosal injury through induction of heat shockprotein 72 and suppression of NF-κB activationrdquo Life Sciencesvol 79 no 24 pp 2245ndash2250 2006
[13] A Bhattacharyya R Chattopadhyay S Mitra and S E CroweldquoOxidative stress an essential factor in the pathogenesis of gas-trointestinal mucosal diseasesrdquo Physiological Reviews vol 94no 2 pp 329ndash354 2014
[14] L Chanudom and J Tangpong ldquoAnti-inflammation propertyof Syzygium cumini (L) Skeels on indomethacin-inducedacute gastric ulcerationrdquo Gastroenterology Research and Prac-tice vol 2015 Article ID 343642 12 pages 2015
[15] L M da Silva A Allemand D A G B Mendes et al ldquoEtha-nolic extract of roots from Arctium lappa L accelerates thehealing of acetic acid-induced gastric ulcer in rats involve-ment of the antioxidant systemrdquo Food and Chemical Toxicol-ogy vol 51 pp 179ndash187 2013
[16] S K Jaiswal C V Rao B Sharma P Mishra S Das andM KDubey ldquoGastroprotective effect of standardized leaf extractfrom Argyreia speciosa on experimental gastric ulcers in ratsrdquoJournal of Ethnopharmacology vol 137 no 1 pp 341ndash3442011
[17] A A El-Fakhry M A El-Daker R I Badr et al ldquoAssociationof the CagA gene positive Helicobacter pylori and tissue levelsof interleukin-17 and interleukin-8 in gastric ulcer patientsrdquoThe Egyptian Journal of Immunology vol 19 no 1 pp 51ndash62 2012
[18] Y W Yin A M Hu Q Q Sun et al ldquoAssociation betweeninterleukin-8 gene minus251 TA polymorphism and the risk ofpeptic ulcer disease a meta-analysisrdquo Human Immunologyvol 74 no 1 pp 125ndash130 2013
[19] S Okabe J L A Roth and C J Pfeiffer ldquoA method for exper-imental penetrating gastric and duodenal ulcers in ratsObservations on normal healingrdquo The American Journal ofDigestive Diseases vol 16 no 3 pp 277ndash284 1971
[20] K Takagi S Okabe and R Saziki ldquoA newmethod for the pro-duction of chronic gastric ulcer in rats and the effect of severaldrugs on its healingrdquo Japanese Journal of Pharmacologyvol 19 no 3 pp 418ndash426 1969
[21] S Okabe and K Amagase ldquoAn overview of acetic acid ulcermodelsmdashthe history and state of the art of peptic ulcerresearchrdquo Biological amp Pharmaceutical Bulletin vol 28no 8 pp 1321ndash1341 2005
8 Gastroenterology Research and Practice
[22] A Tarnawski J Stachura W J Krause T G Douglass andH Gergely ldquoQuality of gastric ulcer healing a new emerg-ing conceptrdquo Journal of Clinical Gastroenterology vol 13Supplement 1 pp S42ndashS47 1991
[23] A S Tarnawski ldquoCellular and molecular mechanisms of gas-trointestinal ulcer healingrdquo Digestive Diseases and Sciencesvol 50 Supplement 1 pp S24ndashS33 2005
[24] M Arun and V V Asha ldquoGastroprotective effect of Dodonaeaviscosa on various experimental ulcer modelsrdquo Journal of Eth-nopharmacology vol 118 no 3 pp 460ndash465 2008
[25] A Alkofahi and A H Atta ldquoPharmacological screening of theanti-ulcerogenic effects of some Jordanian medicinal plants inratsrdquo Journal of Ethnopharmacology vol 67 no 3 pp 341ndash345 1999
[26] S Khennouf H Benabdallah K Gharzouli et al ldquoEffect oftannins from Quercus suber and Quercus coccifera leaves onethanol-induced gastric lesions in micerdquo Journal of Agricul-tural and Food Chemistry vol 51 no 5 pp 1469ndash1473 2003
[27] S Bhattacharya S R Chaudhuri S Chattopadhyay and S KBandyopadhyay ldquoHealing properties of some Indian medici-nal plants against indomethacin-induced gastric ulceration ofratsrdquo Journal of Clinical Biochemistry and Nutrition vol 41no 2 pp 106ndash114 2007
[28] B Q Li T Fu W H Gong et al ldquoThe flavonoid baicalinexhibits anti-inflammatory activity by binding to chemo-kinesrdquo Immunopharmacology vol 49 no 3 pp 295ndash3062000
[29] J Wu D Hu and K X Wang ldquoStudy of Scutellaria baicalensisand Baicalin against antimicrobial susceptibility of Helicobac-ter pylori strains in vitrordquo Zhong yao cai = Zhongyaocai = Jour-nal of Chinese Medicinal Materials vol 31 no 5 pp 707ndash7102008
[30] A M Y Lin Y H Ping G F Chang et al ldquoNeuroprotectiveeffect of oral SB remedy (Scutellaria baicalensis Georgi andBupleurum scorzonerifolfium Willd) on iron-induced neuro-degeneration in the nigrostriatal dopaminergic system of ratbrainrdquo Journal of Ethnopharmacology vol 134 no 3pp 884ndash891 2011
[31] S Y Yoon I C dela Pena C Y Shin et al ldquoConvulsion-related activities of Scutellaria flavones are related to the 57-dihydroxyl structuresrdquo European Journal of Pharmacologyvol 659 no 2-3 pp 155ndash160 2011
[32] L Chen J Dou Z Su et al ldquoSynergistic activity of baicaleinwith ribavirin against influenza A (H1N1) virus infections incell culture and in micerdquo Antiviral Research vol 91 no 3pp 314ndash320 2011
[33] M Li-Weber ldquoNew therapeutic aspects of flavones the anti-cancer properties of Scutellaria and its main active constitu-ents wogonin baicalein and baicalinrdquo Cancer TreatmentReviews vol 35 no 1 pp 57ndash68 2009
[34] D E Shieh L T Liu and C C Lin ldquoAntioxidant and free rad-ical scavenging effects of baicalein baicalin and wogoninrdquoAnticancer Research vol 20 no 5A pp 2861ndash2865 2000
[35] B Bandyopadhyay and S K Bandyopadhyay ldquoProtectiveeffect of zinc gluconate on chemically induced gastric ulcerrdquoThe Indian Journal of Medical Research vol 106 pp 27ndash321997
[36] S S Poulsen ldquoOn the role of epidermal growth factor in thedefence of the gastroduodenal mucosardquo Scandinavian Journalof Gastroenterology vol 128 pp 20ndash23 1987
[37] S Kwiecień T Brzozowski P C H Konturek and S JKonturek ldquoThe role of reactive oxygen species in action ofnitric oxide-donors on stress-induced gastric mucosal lesionsrdquoJournal of Physiology and Pharmacology vol 53 4 Part 2pp 761ndash773 2002
[38] I Chattopadhyay U Bandyopadhyay K Biswas P Maity andR K Banerjee ldquoIndomethacin inactivates gastric peroxidase toinduce reactive-oxygen-mediated gastric mucosal injury andcurcumin protects it by preventing peroxidase inactivationand scavenging reactive oxygenrdquo Free Radical Biology amp Med-icine vol 40 no 8 pp 1397ndash1408 2006
[39] M Maes P Ruckoanich Y S Chang N Mahanonda andM Berk ldquoMultiple aberrations in shared inflammatory andoxidative amp nitrosative stress (IOampNS) pathways explain theco-association of depression and cardiovascular disorder(CVD) and the increased risk for CVD and due mortality indepressed patientsrdquo Progress in Neuro-Psychopharmacologyand Biological Psychiatry vol 35 no 3 pp 769ndash783 2011
Computational and Mathematical Methods in Medicine
Hindawiwwwhindawicom Volume 2018
Behavioural Neurology
OphthalmologyJournal of
Hindawiwwwhindawicom Volume 2018
Diabetes ResearchJournal of
Hindawiwwwhindawicom Volume 2018
Hindawiwwwhindawicom Volume 2018
Research and TreatmentAIDS
Hindawiwwwhindawicom Volume 2018
Gastroenterology Research and Practice
Hindawiwwwhindawicom Volume 2018
Parkinsonrsquos Disease
Evidence-Based Complementary andAlternative Medicine
Volume 2018Hindawiwwwhindawicom
Submit your manuscripts atwwwhindawicom
32 BA-Zn Suppressed Oxidative Stress in Acetic Acid-Induced Gastric Tissue of Rats Increased oxidative stresswas shown in the ulcerated gastric mucosa of the modelgroup and this group also had significantly decreased SODand GSH-Px activities and an increased level of lipid peroxi-dation (MDA) content compared to those of the sham group(P lt 0 001)
As shown in Table 1 SOD activity in the mucosa of themodel group was significantly lower (703plusmn 010Umg pro-tein) than in the sham group (2209plusmn 009Umg proteinP lt 0 001) BA-Zn treatment at 65 and 13mgkg significantlyincreased the SOD activity to 1762plusmn 011 and 2012plusmn 032Umg protein (P lt 0 001 and P lt 0 001) respectively comparedto that of the model group (703plusmn 010Umg protein) More-over the administration of 65 and 13mgkg BA-Zn led tohigher SOD activity than did the administration of BA(1762plusmn 011 and 2012plusmn 032 vs 1209plusmn 013Umg proteinP lt 0 05 and P lt 0 01) and these also markedly increasedSOD activity than that of the zinc-gluconate group (907plusmn033Umg protein P lt 0 001) It indicated that BA-Zn hasa stronger antioxidative effect than BA and zinc-gluconateZinc-gluconate (932mgkg) significantly increased SODactivity to 907plusmn 033Umg protein (P lt 0 05) compared tothat of the model group (703plusmn 010Umg protein) Omep-razole (40mgkg) demonstrated an increase in SOD activity(1932plusmn 009Umg protein P lt 0 001 compared to that ofthe model group)
GSH-Px levels in the gastric mucosa of the model groupwere significantly lower than in the sham group (5221plusmn713 vs 13609plusmn 909Ul P lt 0 001) Administration of 65and 13mgkg BA-Zn significantly increased the GSH-Pxlevel in a dose-dependent manner (P lt 0 001 and P lt 0 001respectively compared to that of the model group) More-over the administration of 65 and 13mgkg BA-Zn led toincreased GSH-Px activity compared to that of the BA group(10212plusmn 911 and12025plusmn 907 vs 8507plusmn 711UlP lt 0 05)and the administration of 65 and 13mgkg BA-Zn alsomarkedly increased GSH-Px activity compared to that ofthe zinc-gluconate group (8035plusmn 677Ul P lt 0 001) Itindicated that BA-Zn has a stronger antioxidative effectthan BA and zinc-gluconate Zinc-gluconate (932mgkg)
significantly increased GSH-Px activity to 8035plusmn 677Ul(P lt 0 05) compared to that of the model group (5221plusmn713Ul) Omeprazole (40mgkg) demonstrated an increasein GSH-Px activity (10712plusmn 905Ul P lt 0 001 comparedto that of the model group)
The inhibitory effects of BA-Zn on lipid peroxidation(MDA) are shown in Table 1 The MDA content in thegastric mucosa of the model group was higher than in thesham group (239plusmn 003 vs 091plusmn 006μmoll P lt 0 001)Treatment with 325 65 and 13mgkg BA-Zn significantlydecreased the MDA content to 175plusmn 007 133plusmn 007 and063plusmn 001μmoll (P lt 0 01 P lt 0 001 and P lt 0 001respectively compared to that of the model group) More-over the administration of 325 65 and 13mgkg BA-Znled to lower MDA activity than BA (175plusmn 007 133plusmn007 and 063plusmn 901 vs 354plusmn 004μmoll P lt 0 05) andthe zinc-gluconate group (200plusmn 012μmoll P lt 0 001)indicating that BA-Zn had a stronger antioxidative effectthan BA and zinc-gluconate Zinc-gluconate (932mgkg)showed a decrease in MDA content (200plusmn 012μmollP lt 0 05 compared to that the model group) Omeprazole(40mgkg) also demonstrated a decrease in MDA con-tent (100plusmn 011μmoll P lt 0 001 compared to that of themodel group)
33 Effect of BA-Zn on the Concentration of TNF-α and IL-8As shown in Table 2 the level of TNF-α in the model groupwas significantly higher than in the sham group (273plusmn 010vs 072plusmn 009 ngml P lt 0 001) The administration of 32565 and 13mgkg BA-Zn significantly decreased the TNF-αconcentration in a dose-dependent manner (195plusmn 006162plusmn 011 and 112plusmn 032 P lt 0 05 P lt 0 001 and P lt0 001 respectively compared to that of the model group)Zinc-gluconate (932mgkg) demonstrated a decreased TNF-α level (200plusmn011ngml P lt 0 05 compared to that of themodel group) Administration of 65 and 13mgkg BA-Zn sig-nificantly decreased the TNF-α concentration compared to thatof the zinc-gluconate group (200plusmn011ngml P lt 0 001)Omeprazole (40mgkg) demonstrated a decreased TNF-αconcentration (132plusmn 009 ngml P lt 0 001 compared to thatof the model group)
CH3
O
OO
O
OO
O
35H2OOH
OH
OH
OH
HO
OZn
Figure 1 Structural formula of BA-Zn
4 Gastroenterology Research and Practice
The level of IL-8 in the model group was significantlyhigher than in the sham group (069plusmn 003 vs 021plusmn006 ngml P lt 0 01) Administration of 325 65 and13mgkg BA-Zn significantly decreased the IL-8 level in adose-dependent manner (036plusmn 007 033plusmn 007 and 029plusmn001 P lt 0 01 P lt 0 01 and P lt 0 001 respectively com-pared to that of the model group) Zinc-gluconate (932mgkg) demonstrated a decreased IL-8 level (060plusmn 001 ngmlP lt 0 05 compared to that of the model group) Administra-tion of 325 65 and 13mgkg BA-Zn significantly decreasedthe IL-8 concentration compared to that of the zinc-gluconate group (060plusmn 001 ngml P lt 0 001) Omeprazole(40mgkg) also demonstrated a decreased IL-8 level (045plusmn001 ngml P lt 0 05 compared to the model group)
To further demonstrate the effect of BA-Zn on the con-centration of SOD TNF-α and IL-8 in the above groupsWestern blot assays were used to detect the expression levelsof these proteins In Figure 4(a) and 4(b) we reveal thatBA-Zn treatment significantly increased SOD expression
compared to that in the model and zinc-gluconate groupsBA-Zn also significantly decreased the expression of TNF-αand IL-8 compared to that in the model and zinc-gluconategroups In summary the above results indicate that BA-Znhad better antioxidative and anti-inflammatory effects thanboth BA and zinc-gluconate
4 Discussion
Gastric ulcer is a common dysfunction of the digestive sys-tem and an increasing number of people worldwide are suf-fering damage from ulcers The acetic acid-induced ulcermodel resembles human chronic ulcers in both pathologicalfeatures and aspects of the healing process [20 21] thus itis themostusefulmodel forus tousewhen investigating gastriculcers Previous studies have demonstrated that experimentalgastric ulcers have many histological and ultrastructuralabnormalities including a reduced height marked dilationof gastric glands and increased connective tissue that may
(a) (b) (c)
(d) (e) (f)
(g) (h)
Figure 2 Appearances of acetic acid-induced gastric ulcers in different groups (a) the sham group treated daily with water (b) an ulcerationfrom the model group induced by acetic acid (cndashe) an ulceration from the BA-Zn group induced by acetic acid and treated daily with BA-Zn(325 65 and 13mgkg po) (f) an ulceration from the BA group induced by acetic acid and treated daily with BA (46mgkg po) (g) anulceration from the zinc-gluconate group induced by acetic acid and treated daily with zinc-gluconate (932mgkg po) and (h) an ulcerationfrom the omeprazole group induced by acetic acid and treated daily with omeprazole (40mgkg po) Black arrows indicate ulcer location
5Gastroenterology Research and Practice
interfere with the mucosal defense system and cause ulcerrecurrence with some ulcerogenic factors [22 23]
In recent years chemical drugs used for the treatmentof gastric ulcers have induced many side effects Recentlynewly developed drugs with herbal origins may offerreduced side effects compared with chemical drugs [24]
In folk knowledge medicinal plants have been used forthe treatment of various disorders More and more medic-inal plants with various therapeutic properties especially forthe treatment of gastritis and gastric ulcers have been identi-fied [25ndash27] However few traditional Chinese medicinalplants for gastric ulcer treatment have been studied Cur-rently because of the lack of effective and applicable pharma-cological treatments for gastric ulcer more and more peoplehave focused on traditional medicines The investigation ofthe therapeutic functions of traditional medicinal herbs ingastric ulcer offer promising potential
Scutellaria baicalensis is a popular medicinal herb used intraditional Chinese medicine and it is used for the treatmentof high fevers ulcers inflammation and even cancer Themain bioactive flavonoids in Scutellaria baicalensis includebaicalein baicalin (BA) (baicalein-7-glucuronide) wogoninwogonoside (wogonin-7-glucuronide) oroxylin A and orox-ylin A-7-glucuronide Scutellaria baicalensis and its flavoneshave been studied for their various pharmacological activi-ties including anti-inflammatory [28] antibacterial [29]neuroprotective [30] anticonvulsant [31] antiviral [32]antitumor [33] and antioxidant [34] activities BA is themostpopular bioactive flavonoid for treating ulcers However the
(a) (b) (c)
(d) (e) (f)
(g) (h)
Figure 3 Photomicrographs of acetic acid-induced gastric ulcers from different groups (a) sham group (b) HE staining of the model groupinduced by acetic acid (cndashe) HE staining of the BA-Zn group induced by acetic acid and treated daily with BA-Zn (325 65 and 13mgkgpo) (f) HE staining of the BA group induced by acetic acid and treated daily with BA (46mgkg po) (g) HE staining of the zinc-gluconategroup induced by acetic acid and treated daily with zinc-gluconate (932mgkg po) and (h) HE staining of the omeprazole group inducedby acetic acid and treated daily with omeprazole (40mgkg po) The HE stained slides were visualized under a bright field microscopewith 20x magnification
Table 2 Concentration of TNF-α and IL-8 in rat mucosa inducedby acetic acid
Omeprazole 4 132plusmn 009lowastlowastlowast 045plusmn 001lowastlowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
6 Gastroenterology Research and Practice
antichronic gastric ulcer effects of BA alone or in complexhave not yet been elucidated
In this paper we examined the effects of BA-Zn BA andzinc-gluconate and related mechanisms on gastric ulcer heal-ing in an acetic acid-induced gastric ulcer rat model It hasbeen reported that zinc-gluconate has a protective effect ongastric ulcers [35] Acetic acid induces a state of acute stressin the gastric mucosa subsequently inducing gastric ulcersMoreover acetic acid-induced gastric ulceration leads tochronic oxidative stress with decreased SOD activity andGSH-Px expression levels and increased lipid peroxidation(MDA) It is well known that SOD GSH-Px and MDA playimportant roles in protecting the gastric mucosa against var-ious damaging agents [36 37] GSH-Px also plays an impor-tant role in protecting against oxidative gastric mucosalinjury [38] MDA is currently regarded as a reliable indexof ROS-induced mucosal injury [39] Therefore the detec-tion of SOD GSH-Px and MDA contents can reflect andindicate the level of oxidative stress In addition increasedconcentrations of TNF-α and IL-8 were detected in the ulcer-ated gastric mucosa BA-Zn (13mgkg) significantly acceler-ated the healing of gastric ulcers through an increase in SODand GSH-Px activity and a decrease in MDA IL-8 and TNF-α contents We also detected the levels of SOD IL-8 andTNF-α by Western blot We found that BA-Zn significantlyaccelerated ulcer healing by decreasing oxidative stress andattenuating inflammation In our results zinc-gluconate alsohas a protective effect on gastric ulcers but BA-Zn has much
stronger protective and healing abilities in gastric ulcers Onthe basis of our data BA-Zn (13mgkg) has greater antigas-tric ulcer abilities than either BA or zinc-gluconate
Collectively BA-Zn presents important ulcer-healingproperties in the model of chronic ulcer induced by aceticacid in rats Omeprazole is one of the most popular drugsused for the therapeutic control of gastroduodenal ulcers inhumans In our work BA-Zn also exerted an antiulcerogeniceffect similar to that of omeprazole against the developmentof acetic acid-induced gastric ulcers in rats using antioxidantand anti-inflammatory abilities Therefore the BA-Zn com-plex may become a potential and promising drug for thetreatment of human gastroduodenal ulcers In summaryour study indicates that BA-Zn promotes ulcer healing bydecreasing oxidative stress and attenuating inflammation inan acetic acid-induced gastric ulcer rat model Howeveradditional studies are needed to explore the novel mecha-nisms of BA-Zn and determine whether other mechanismsare also involved in the antiulcer effects of this complex
5 Conclusion
In conclusion BA-Zn facilitates the healing of acetic-inducedchronic ulcers in rats through its antioxidant and anti-inflammatory properties The results of this study provide afoundation for the clinical application of BA-Zn in the treat-ment of gastroduodenal ulcers
SOD
IL-8
TNF-훼
훽-Actin
Sham Model BA O325
BA-Zn (mgkg)
Z1365
(a)
SOD25
2015100500
Sham
Mod
el BA 325 6
5
BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Sham
Mod
el BA 325 6
5BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Sham
Mod
el BA 325 6
5
BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Prot
ein
leve
l
20
15
10
05
00
Prot
ein
leve
l20
15
10
05
00
Prot
ein
leve
l
IL-8 TNF-훼
(b)
Figure 4 Western blot analysis of SOD TNF-α and IL-8 expression (a) The protein expression levels of SOD TNF-α and IL-8 wereanalyzed by Western blot analysis β-Actin was used as a loading control (b) Quantification of SOD TNF-α and IL-8 protein expressionlevels using ImageJ software Z zinc-gluconate O omeprazole lowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
7Gastroenterology Research and Practice
Data Availability
The data used to support the findings of this study are avail-able from the corresponding author upon request
Conflicts of Interest
The authors declare that there are no conflicts of interest andno financial conflicts regarding the publication of this paper
Authorsrsquo Contributions
This study was designed by Xu Liu Experimental work wasdone by Hui Yang Zhong-Kun Ren Yi Lu Xiao-Feng Zengand Ling Li The first draft of this paper was written by HuiYang and reviewed by Xu Liu and Rong-Ping ZhangZhong-Kun Ren and Yi Lu reviewed the methodology andresults All authors reviewed and approved the final version
Acknowledgments
The present study was supported by the Yunnan AppliedBasic Research Projects (Grant no 2005C00092)
References
[1] J L Goldstein J Aisenberg F Lanza et al ldquoA multicenterrandomized double-blind active-comparator placebo-con-trolled parallel-group comparison of the incidence of endo-scopic gastric and duodenal ulcer rates with valdecoxib ornaproxen in healthy subjects aged 65 to 75 yearsrdquo ClinicalTherapeutics vol 28 no 3 pp 340ndash351 2006
[2] G H Heeba M K A Hassan and R S Amin ldquoGastroprotec-tive effect of simvastatin against indomethacin-induced gastriculcer in rats role of nitric oxide and prostaglandinsrdquo EuropeanJournal of Pharmacology vol 607 no 1ndash3 pp 188ndash193 2009
[3] P A Gladding M W I Webster H B Farrell I S L ZengR Park and N Ruijne ldquoThe antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacody-namic interaction with aspirin in healthy volunteersrdquo TheAmerican Journal of Cardiology vol 101 no 7 pp 1060ndash1063 2008
[4] A Lanas M A Perez-Aisa F Feu et al ldquoA nationwide studyof mortality associated with hospital admission due to severegastrointestinal events and those associated with nonsteroidalantiinflammatory drug userdquo The American Journal of Gastro-enterology vol 100 no 8 pp 1685ndash1693 2005
[5] B Cryer and K W Mahaffey ldquoGastrointestinal ulcers role ofaspirin and clinical outcomes pathobiology diagnosis andtreatmentrdquo Journal of Multidisciplinary Healthcare vol 7pp 137ndash146 2014
[6] J Lu J S Wang and L Y Kong ldquoAnti-inflammatory effects ofHuang-Lian-Jie-Du decoction its two fractions and four typi-cal compoundsrdquo Journal of Ethnopharmacology vol 134no 3 pp 911ndash918 2011
[7] J M Hwang T H Tseng Y Y Tsai et al ldquoProtective effects ofbaicalein on tert-butyl hydroperoxide-induced hepatic toxicityin rat hepatocytesrdquo Journal of Biomedical Science vol 12no 2 pp 389ndash397 2005
[8] J Dou L Chen G Xu et al ldquoEffects of baicalein on Sendaivirus in vivo are linked to serum baicalin and its inhibition
of hemagglutinin-neuraminidaserdquo Archives of Virologyvol 156 no 5 pp 793ndash801 2011
[9] M Y Yun J H Yang D K Kim et al ldquoTherapeutic effects ofbaicalein on atopic dermatitis-like skin lesions of NCNgamice induced by Dermatophagoides pteronyssinusrdquo Interna-tional Immunopharmacology vol 10 no 9 pp 1142ndash11482010
[10] J H Liu H Wann M M Chen et al ldquoBaicalein signifi-cantly protects human retinal pigment epithelium cellsagainst H2O2-induced oxidative stress by scavenging reac-tive oxygen species and downregulating the expression ofmatrix metalloproteinase-9 and vascular endothelial growthfactorrdquo Journal of Ocular Pharmacology and Therapeuticsvol 26 no 5 pp 421ndash429 2010
[11] P D Zalewski A Q Truong-Tran D Grosser L JayaramC Murgia and R E Ruffin ldquoZinc metabolism in airway epi-thelium and airway inflammation basic mechanisms and clin-ical targets A reviewrdquo Pharmacology amp Therapeutics vol 105no 2 pp 127ndash149 2005
[12] M Odashima M Otaka M Jin et al ldquoZinc L-carnosine pro-tects colonic mucosal injury through induction of heat shockprotein 72 and suppression of NF-κB activationrdquo Life Sciencesvol 79 no 24 pp 2245ndash2250 2006
[13] A Bhattacharyya R Chattopadhyay S Mitra and S E CroweldquoOxidative stress an essential factor in the pathogenesis of gas-trointestinal mucosal diseasesrdquo Physiological Reviews vol 94no 2 pp 329ndash354 2014
[14] L Chanudom and J Tangpong ldquoAnti-inflammation propertyof Syzygium cumini (L) Skeels on indomethacin-inducedacute gastric ulcerationrdquo Gastroenterology Research and Prac-tice vol 2015 Article ID 343642 12 pages 2015
[15] L M da Silva A Allemand D A G B Mendes et al ldquoEtha-nolic extract of roots from Arctium lappa L accelerates thehealing of acetic acid-induced gastric ulcer in rats involve-ment of the antioxidant systemrdquo Food and Chemical Toxicol-ogy vol 51 pp 179ndash187 2013
[16] S K Jaiswal C V Rao B Sharma P Mishra S Das andM KDubey ldquoGastroprotective effect of standardized leaf extractfrom Argyreia speciosa on experimental gastric ulcers in ratsrdquoJournal of Ethnopharmacology vol 137 no 1 pp 341ndash3442011
[17] A A El-Fakhry M A El-Daker R I Badr et al ldquoAssociationof the CagA gene positive Helicobacter pylori and tissue levelsof interleukin-17 and interleukin-8 in gastric ulcer patientsrdquoThe Egyptian Journal of Immunology vol 19 no 1 pp 51ndash62 2012
[18] Y W Yin A M Hu Q Q Sun et al ldquoAssociation betweeninterleukin-8 gene minus251 TA polymorphism and the risk ofpeptic ulcer disease a meta-analysisrdquo Human Immunologyvol 74 no 1 pp 125ndash130 2013
[19] S Okabe J L A Roth and C J Pfeiffer ldquoA method for exper-imental penetrating gastric and duodenal ulcers in ratsObservations on normal healingrdquo The American Journal ofDigestive Diseases vol 16 no 3 pp 277ndash284 1971
[20] K Takagi S Okabe and R Saziki ldquoA newmethod for the pro-duction of chronic gastric ulcer in rats and the effect of severaldrugs on its healingrdquo Japanese Journal of Pharmacologyvol 19 no 3 pp 418ndash426 1969
[21] S Okabe and K Amagase ldquoAn overview of acetic acid ulcermodelsmdashthe history and state of the art of peptic ulcerresearchrdquo Biological amp Pharmaceutical Bulletin vol 28no 8 pp 1321ndash1341 2005
8 Gastroenterology Research and Practice
[22] A Tarnawski J Stachura W J Krause T G Douglass andH Gergely ldquoQuality of gastric ulcer healing a new emerg-ing conceptrdquo Journal of Clinical Gastroenterology vol 13Supplement 1 pp S42ndashS47 1991
[23] A S Tarnawski ldquoCellular and molecular mechanisms of gas-trointestinal ulcer healingrdquo Digestive Diseases and Sciencesvol 50 Supplement 1 pp S24ndashS33 2005
[24] M Arun and V V Asha ldquoGastroprotective effect of Dodonaeaviscosa on various experimental ulcer modelsrdquo Journal of Eth-nopharmacology vol 118 no 3 pp 460ndash465 2008
[25] A Alkofahi and A H Atta ldquoPharmacological screening of theanti-ulcerogenic effects of some Jordanian medicinal plants inratsrdquo Journal of Ethnopharmacology vol 67 no 3 pp 341ndash345 1999
[26] S Khennouf H Benabdallah K Gharzouli et al ldquoEffect oftannins from Quercus suber and Quercus coccifera leaves onethanol-induced gastric lesions in micerdquo Journal of Agricul-tural and Food Chemistry vol 51 no 5 pp 1469ndash1473 2003
[27] S Bhattacharya S R Chaudhuri S Chattopadhyay and S KBandyopadhyay ldquoHealing properties of some Indian medici-nal plants against indomethacin-induced gastric ulceration ofratsrdquo Journal of Clinical Biochemistry and Nutrition vol 41no 2 pp 106ndash114 2007
[28] B Q Li T Fu W H Gong et al ldquoThe flavonoid baicalinexhibits anti-inflammatory activity by binding to chemo-kinesrdquo Immunopharmacology vol 49 no 3 pp 295ndash3062000
[29] J Wu D Hu and K X Wang ldquoStudy of Scutellaria baicalensisand Baicalin against antimicrobial susceptibility of Helicobac-ter pylori strains in vitrordquo Zhong yao cai = Zhongyaocai = Jour-nal of Chinese Medicinal Materials vol 31 no 5 pp 707ndash7102008
[30] A M Y Lin Y H Ping G F Chang et al ldquoNeuroprotectiveeffect of oral SB remedy (Scutellaria baicalensis Georgi andBupleurum scorzonerifolfium Willd) on iron-induced neuro-degeneration in the nigrostriatal dopaminergic system of ratbrainrdquo Journal of Ethnopharmacology vol 134 no 3pp 884ndash891 2011
[31] S Y Yoon I C dela Pena C Y Shin et al ldquoConvulsion-related activities of Scutellaria flavones are related to the 57-dihydroxyl structuresrdquo European Journal of Pharmacologyvol 659 no 2-3 pp 155ndash160 2011
[32] L Chen J Dou Z Su et al ldquoSynergistic activity of baicaleinwith ribavirin against influenza A (H1N1) virus infections incell culture and in micerdquo Antiviral Research vol 91 no 3pp 314ndash320 2011
[33] M Li-Weber ldquoNew therapeutic aspects of flavones the anti-cancer properties of Scutellaria and its main active constitu-ents wogonin baicalein and baicalinrdquo Cancer TreatmentReviews vol 35 no 1 pp 57ndash68 2009
[34] D E Shieh L T Liu and C C Lin ldquoAntioxidant and free rad-ical scavenging effects of baicalein baicalin and wogoninrdquoAnticancer Research vol 20 no 5A pp 2861ndash2865 2000
[35] B Bandyopadhyay and S K Bandyopadhyay ldquoProtectiveeffect of zinc gluconate on chemically induced gastric ulcerrdquoThe Indian Journal of Medical Research vol 106 pp 27ndash321997
[36] S S Poulsen ldquoOn the role of epidermal growth factor in thedefence of the gastroduodenal mucosardquo Scandinavian Journalof Gastroenterology vol 128 pp 20ndash23 1987
[37] S Kwiecień T Brzozowski P C H Konturek and S JKonturek ldquoThe role of reactive oxygen species in action ofnitric oxide-donors on stress-induced gastric mucosal lesionsrdquoJournal of Physiology and Pharmacology vol 53 4 Part 2pp 761ndash773 2002
[38] I Chattopadhyay U Bandyopadhyay K Biswas P Maity andR K Banerjee ldquoIndomethacin inactivates gastric peroxidase toinduce reactive-oxygen-mediated gastric mucosal injury andcurcumin protects it by preventing peroxidase inactivationand scavenging reactive oxygenrdquo Free Radical Biology amp Med-icine vol 40 no 8 pp 1397ndash1408 2006
[39] M Maes P Ruckoanich Y S Chang N Mahanonda andM Berk ldquoMultiple aberrations in shared inflammatory andoxidative amp nitrosative stress (IOampNS) pathways explain theco-association of depression and cardiovascular disorder(CVD) and the increased risk for CVD and due mortality indepressed patientsrdquo Progress in Neuro-Psychopharmacologyand Biological Psychiatry vol 35 no 3 pp 769ndash783 2011
Computational and Mathematical Methods in Medicine
Hindawiwwwhindawicom Volume 2018
Behavioural Neurology
OphthalmologyJournal of
Hindawiwwwhindawicom Volume 2018
Diabetes ResearchJournal of
Hindawiwwwhindawicom Volume 2018
Hindawiwwwhindawicom Volume 2018
Research and TreatmentAIDS
Hindawiwwwhindawicom Volume 2018
Gastroenterology Research and Practice
Hindawiwwwhindawicom Volume 2018
Parkinsonrsquos Disease
Evidence-Based Complementary andAlternative Medicine
Volume 2018Hindawiwwwhindawicom
Submit your manuscripts atwwwhindawicom
The level of IL-8 in the model group was significantlyhigher than in the sham group (069plusmn 003 vs 021plusmn006 ngml P lt 0 01) Administration of 325 65 and13mgkg BA-Zn significantly decreased the IL-8 level in adose-dependent manner (036plusmn 007 033plusmn 007 and 029plusmn001 P lt 0 01 P lt 0 01 and P lt 0 001 respectively com-pared to that of the model group) Zinc-gluconate (932mgkg) demonstrated a decreased IL-8 level (060plusmn 001 ngmlP lt 0 05 compared to that of the model group) Administra-tion of 325 65 and 13mgkg BA-Zn significantly decreasedthe IL-8 concentration compared to that of the zinc-gluconate group (060plusmn 001 ngml P lt 0 001) Omeprazole(40mgkg) also demonstrated a decreased IL-8 level (045plusmn001 ngml P lt 0 05 compared to the model group)
To further demonstrate the effect of BA-Zn on the con-centration of SOD TNF-α and IL-8 in the above groupsWestern blot assays were used to detect the expression levelsof these proteins In Figure 4(a) and 4(b) we reveal thatBA-Zn treatment significantly increased SOD expression
compared to that in the model and zinc-gluconate groupsBA-Zn also significantly decreased the expression of TNF-αand IL-8 compared to that in the model and zinc-gluconategroups In summary the above results indicate that BA-Znhad better antioxidative and anti-inflammatory effects thanboth BA and zinc-gluconate
4 Discussion
Gastric ulcer is a common dysfunction of the digestive sys-tem and an increasing number of people worldwide are suf-fering damage from ulcers The acetic acid-induced ulcermodel resembles human chronic ulcers in both pathologicalfeatures and aspects of the healing process [20 21] thus itis themostusefulmodel forus tousewhen investigating gastriculcers Previous studies have demonstrated that experimentalgastric ulcers have many histological and ultrastructuralabnormalities including a reduced height marked dilationof gastric glands and increased connective tissue that may
(a) (b) (c)
(d) (e) (f)
(g) (h)
Figure 2 Appearances of acetic acid-induced gastric ulcers in different groups (a) the sham group treated daily with water (b) an ulcerationfrom the model group induced by acetic acid (cndashe) an ulceration from the BA-Zn group induced by acetic acid and treated daily with BA-Zn(325 65 and 13mgkg po) (f) an ulceration from the BA group induced by acetic acid and treated daily with BA (46mgkg po) (g) anulceration from the zinc-gluconate group induced by acetic acid and treated daily with zinc-gluconate (932mgkg po) and (h) an ulcerationfrom the omeprazole group induced by acetic acid and treated daily with omeprazole (40mgkg po) Black arrows indicate ulcer location
5Gastroenterology Research and Practice
interfere with the mucosal defense system and cause ulcerrecurrence with some ulcerogenic factors [22 23]
In recent years chemical drugs used for the treatmentof gastric ulcers have induced many side effects Recentlynewly developed drugs with herbal origins may offerreduced side effects compared with chemical drugs [24]
In folk knowledge medicinal plants have been used forthe treatment of various disorders More and more medic-inal plants with various therapeutic properties especially forthe treatment of gastritis and gastric ulcers have been identi-fied [25ndash27] However few traditional Chinese medicinalplants for gastric ulcer treatment have been studied Cur-rently because of the lack of effective and applicable pharma-cological treatments for gastric ulcer more and more peoplehave focused on traditional medicines The investigation ofthe therapeutic functions of traditional medicinal herbs ingastric ulcer offer promising potential
Scutellaria baicalensis is a popular medicinal herb used intraditional Chinese medicine and it is used for the treatmentof high fevers ulcers inflammation and even cancer Themain bioactive flavonoids in Scutellaria baicalensis includebaicalein baicalin (BA) (baicalein-7-glucuronide) wogoninwogonoside (wogonin-7-glucuronide) oroxylin A and orox-ylin A-7-glucuronide Scutellaria baicalensis and its flavoneshave been studied for their various pharmacological activi-ties including anti-inflammatory [28] antibacterial [29]neuroprotective [30] anticonvulsant [31] antiviral [32]antitumor [33] and antioxidant [34] activities BA is themostpopular bioactive flavonoid for treating ulcers However the
(a) (b) (c)
(d) (e) (f)
(g) (h)
Figure 3 Photomicrographs of acetic acid-induced gastric ulcers from different groups (a) sham group (b) HE staining of the model groupinduced by acetic acid (cndashe) HE staining of the BA-Zn group induced by acetic acid and treated daily with BA-Zn (325 65 and 13mgkgpo) (f) HE staining of the BA group induced by acetic acid and treated daily with BA (46mgkg po) (g) HE staining of the zinc-gluconategroup induced by acetic acid and treated daily with zinc-gluconate (932mgkg po) and (h) HE staining of the omeprazole group inducedby acetic acid and treated daily with omeprazole (40mgkg po) The HE stained slides were visualized under a bright field microscopewith 20x magnification
Table 2 Concentration of TNF-α and IL-8 in rat mucosa inducedby acetic acid
Omeprazole 4 132plusmn 009lowastlowastlowast 045plusmn 001lowastlowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
6 Gastroenterology Research and Practice
antichronic gastric ulcer effects of BA alone or in complexhave not yet been elucidated
In this paper we examined the effects of BA-Zn BA andzinc-gluconate and related mechanisms on gastric ulcer heal-ing in an acetic acid-induced gastric ulcer rat model It hasbeen reported that zinc-gluconate has a protective effect ongastric ulcers [35] Acetic acid induces a state of acute stressin the gastric mucosa subsequently inducing gastric ulcersMoreover acetic acid-induced gastric ulceration leads tochronic oxidative stress with decreased SOD activity andGSH-Px expression levels and increased lipid peroxidation(MDA) It is well known that SOD GSH-Px and MDA playimportant roles in protecting the gastric mucosa against var-ious damaging agents [36 37] GSH-Px also plays an impor-tant role in protecting against oxidative gastric mucosalinjury [38] MDA is currently regarded as a reliable indexof ROS-induced mucosal injury [39] Therefore the detec-tion of SOD GSH-Px and MDA contents can reflect andindicate the level of oxidative stress In addition increasedconcentrations of TNF-α and IL-8 were detected in the ulcer-ated gastric mucosa BA-Zn (13mgkg) significantly acceler-ated the healing of gastric ulcers through an increase in SODand GSH-Px activity and a decrease in MDA IL-8 and TNF-α contents We also detected the levels of SOD IL-8 andTNF-α by Western blot We found that BA-Zn significantlyaccelerated ulcer healing by decreasing oxidative stress andattenuating inflammation In our results zinc-gluconate alsohas a protective effect on gastric ulcers but BA-Zn has much
stronger protective and healing abilities in gastric ulcers Onthe basis of our data BA-Zn (13mgkg) has greater antigas-tric ulcer abilities than either BA or zinc-gluconate
Collectively BA-Zn presents important ulcer-healingproperties in the model of chronic ulcer induced by aceticacid in rats Omeprazole is one of the most popular drugsused for the therapeutic control of gastroduodenal ulcers inhumans In our work BA-Zn also exerted an antiulcerogeniceffect similar to that of omeprazole against the developmentof acetic acid-induced gastric ulcers in rats using antioxidantand anti-inflammatory abilities Therefore the BA-Zn com-plex may become a potential and promising drug for thetreatment of human gastroduodenal ulcers In summaryour study indicates that BA-Zn promotes ulcer healing bydecreasing oxidative stress and attenuating inflammation inan acetic acid-induced gastric ulcer rat model Howeveradditional studies are needed to explore the novel mecha-nisms of BA-Zn and determine whether other mechanismsare also involved in the antiulcer effects of this complex
5 Conclusion
In conclusion BA-Zn facilitates the healing of acetic-inducedchronic ulcers in rats through its antioxidant and anti-inflammatory properties The results of this study provide afoundation for the clinical application of BA-Zn in the treat-ment of gastroduodenal ulcers
SOD
IL-8
TNF-훼
훽-Actin
Sham Model BA O325
BA-Zn (mgkg)
Z1365
(a)
SOD25
2015100500
Sham
Mod
el BA 325 6
5
BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Sham
Mod
el BA 325 6
5BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Sham
Mod
el BA 325 6
5
BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Prot
ein
leve
l
20
15
10
05
00
Prot
ein
leve
l20
15
10
05
00
Prot
ein
leve
l
IL-8 TNF-훼
(b)
Figure 4 Western blot analysis of SOD TNF-α and IL-8 expression (a) The protein expression levels of SOD TNF-α and IL-8 wereanalyzed by Western blot analysis β-Actin was used as a loading control (b) Quantification of SOD TNF-α and IL-8 protein expressionlevels using ImageJ software Z zinc-gluconate O omeprazole lowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
7Gastroenterology Research and Practice
Data Availability
The data used to support the findings of this study are avail-able from the corresponding author upon request
Conflicts of Interest
The authors declare that there are no conflicts of interest andno financial conflicts regarding the publication of this paper
Authorsrsquo Contributions
This study was designed by Xu Liu Experimental work wasdone by Hui Yang Zhong-Kun Ren Yi Lu Xiao-Feng Zengand Ling Li The first draft of this paper was written by HuiYang and reviewed by Xu Liu and Rong-Ping ZhangZhong-Kun Ren and Yi Lu reviewed the methodology andresults All authors reviewed and approved the final version
Acknowledgments
The present study was supported by the Yunnan AppliedBasic Research Projects (Grant no 2005C00092)
References
[1] J L Goldstein J Aisenberg F Lanza et al ldquoA multicenterrandomized double-blind active-comparator placebo-con-trolled parallel-group comparison of the incidence of endo-scopic gastric and duodenal ulcer rates with valdecoxib ornaproxen in healthy subjects aged 65 to 75 yearsrdquo ClinicalTherapeutics vol 28 no 3 pp 340ndash351 2006
[2] G H Heeba M K A Hassan and R S Amin ldquoGastroprotec-tive effect of simvastatin against indomethacin-induced gastriculcer in rats role of nitric oxide and prostaglandinsrdquo EuropeanJournal of Pharmacology vol 607 no 1ndash3 pp 188ndash193 2009
[3] P A Gladding M W I Webster H B Farrell I S L ZengR Park and N Ruijne ldquoThe antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacody-namic interaction with aspirin in healthy volunteersrdquo TheAmerican Journal of Cardiology vol 101 no 7 pp 1060ndash1063 2008
[4] A Lanas M A Perez-Aisa F Feu et al ldquoA nationwide studyof mortality associated with hospital admission due to severegastrointestinal events and those associated with nonsteroidalantiinflammatory drug userdquo The American Journal of Gastro-enterology vol 100 no 8 pp 1685ndash1693 2005
[5] B Cryer and K W Mahaffey ldquoGastrointestinal ulcers role ofaspirin and clinical outcomes pathobiology diagnosis andtreatmentrdquo Journal of Multidisciplinary Healthcare vol 7pp 137ndash146 2014
[6] J Lu J S Wang and L Y Kong ldquoAnti-inflammatory effects ofHuang-Lian-Jie-Du decoction its two fractions and four typi-cal compoundsrdquo Journal of Ethnopharmacology vol 134no 3 pp 911ndash918 2011
[7] J M Hwang T H Tseng Y Y Tsai et al ldquoProtective effects ofbaicalein on tert-butyl hydroperoxide-induced hepatic toxicityin rat hepatocytesrdquo Journal of Biomedical Science vol 12no 2 pp 389ndash397 2005
[8] J Dou L Chen G Xu et al ldquoEffects of baicalein on Sendaivirus in vivo are linked to serum baicalin and its inhibition
of hemagglutinin-neuraminidaserdquo Archives of Virologyvol 156 no 5 pp 793ndash801 2011
[9] M Y Yun J H Yang D K Kim et al ldquoTherapeutic effects ofbaicalein on atopic dermatitis-like skin lesions of NCNgamice induced by Dermatophagoides pteronyssinusrdquo Interna-tional Immunopharmacology vol 10 no 9 pp 1142ndash11482010
[10] J H Liu H Wann M M Chen et al ldquoBaicalein signifi-cantly protects human retinal pigment epithelium cellsagainst H2O2-induced oxidative stress by scavenging reac-tive oxygen species and downregulating the expression ofmatrix metalloproteinase-9 and vascular endothelial growthfactorrdquo Journal of Ocular Pharmacology and Therapeuticsvol 26 no 5 pp 421ndash429 2010
[11] P D Zalewski A Q Truong-Tran D Grosser L JayaramC Murgia and R E Ruffin ldquoZinc metabolism in airway epi-thelium and airway inflammation basic mechanisms and clin-ical targets A reviewrdquo Pharmacology amp Therapeutics vol 105no 2 pp 127ndash149 2005
[12] M Odashima M Otaka M Jin et al ldquoZinc L-carnosine pro-tects colonic mucosal injury through induction of heat shockprotein 72 and suppression of NF-κB activationrdquo Life Sciencesvol 79 no 24 pp 2245ndash2250 2006
[13] A Bhattacharyya R Chattopadhyay S Mitra and S E CroweldquoOxidative stress an essential factor in the pathogenesis of gas-trointestinal mucosal diseasesrdquo Physiological Reviews vol 94no 2 pp 329ndash354 2014
[14] L Chanudom and J Tangpong ldquoAnti-inflammation propertyof Syzygium cumini (L) Skeels on indomethacin-inducedacute gastric ulcerationrdquo Gastroenterology Research and Prac-tice vol 2015 Article ID 343642 12 pages 2015
[15] L M da Silva A Allemand D A G B Mendes et al ldquoEtha-nolic extract of roots from Arctium lappa L accelerates thehealing of acetic acid-induced gastric ulcer in rats involve-ment of the antioxidant systemrdquo Food and Chemical Toxicol-ogy vol 51 pp 179ndash187 2013
[16] S K Jaiswal C V Rao B Sharma P Mishra S Das andM KDubey ldquoGastroprotective effect of standardized leaf extractfrom Argyreia speciosa on experimental gastric ulcers in ratsrdquoJournal of Ethnopharmacology vol 137 no 1 pp 341ndash3442011
[17] A A El-Fakhry M A El-Daker R I Badr et al ldquoAssociationof the CagA gene positive Helicobacter pylori and tissue levelsof interleukin-17 and interleukin-8 in gastric ulcer patientsrdquoThe Egyptian Journal of Immunology vol 19 no 1 pp 51ndash62 2012
[18] Y W Yin A M Hu Q Q Sun et al ldquoAssociation betweeninterleukin-8 gene minus251 TA polymorphism and the risk ofpeptic ulcer disease a meta-analysisrdquo Human Immunologyvol 74 no 1 pp 125ndash130 2013
[19] S Okabe J L A Roth and C J Pfeiffer ldquoA method for exper-imental penetrating gastric and duodenal ulcers in ratsObservations on normal healingrdquo The American Journal ofDigestive Diseases vol 16 no 3 pp 277ndash284 1971
[20] K Takagi S Okabe and R Saziki ldquoA newmethod for the pro-duction of chronic gastric ulcer in rats and the effect of severaldrugs on its healingrdquo Japanese Journal of Pharmacologyvol 19 no 3 pp 418ndash426 1969
[21] S Okabe and K Amagase ldquoAn overview of acetic acid ulcermodelsmdashthe history and state of the art of peptic ulcerresearchrdquo Biological amp Pharmaceutical Bulletin vol 28no 8 pp 1321ndash1341 2005
8 Gastroenterology Research and Practice
[22] A Tarnawski J Stachura W J Krause T G Douglass andH Gergely ldquoQuality of gastric ulcer healing a new emerg-ing conceptrdquo Journal of Clinical Gastroenterology vol 13Supplement 1 pp S42ndashS47 1991
[23] A S Tarnawski ldquoCellular and molecular mechanisms of gas-trointestinal ulcer healingrdquo Digestive Diseases and Sciencesvol 50 Supplement 1 pp S24ndashS33 2005
[24] M Arun and V V Asha ldquoGastroprotective effect of Dodonaeaviscosa on various experimental ulcer modelsrdquo Journal of Eth-nopharmacology vol 118 no 3 pp 460ndash465 2008
[25] A Alkofahi and A H Atta ldquoPharmacological screening of theanti-ulcerogenic effects of some Jordanian medicinal plants inratsrdquo Journal of Ethnopharmacology vol 67 no 3 pp 341ndash345 1999
[26] S Khennouf H Benabdallah K Gharzouli et al ldquoEffect oftannins from Quercus suber and Quercus coccifera leaves onethanol-induced gastric lesions in micerdquo Journal of Agricul-tural and Food Chemistry vol 51 no 5 pp 1469ndash1473 2003
[27] S Bhattacharya S R Chaudhuri S Chattopadhyay and S KBandyopadhyay ldquoHealing properties of some Indian medici-nal plants against indomethacin-induced gastric ulceration ofratsrdquo Journal of Clinical Biochemistry and Nutrition vol 41no 2 pp 106ndash114 2007
[28] B Q Li T Fu W H Gong et al ldquoThe flavonoid baicalinexhibits anti-inflammatory activity by binding to chemo-kinesrdquo Immunopharmacology vol 49 no 3 pp 295ndash3062000
[29] J Wu D Hu and K X Wang ldquoStudy of Scutellaria baicalensisand Baicalin against antimicrobial susceptibility of Helicobac-ter pylori strains in vitrordquo Zhong yao cai = Zhongyaocai = Jour-nal of Chinese Medicinal Materials vol 31 no 5 pp 707ndash7102008
[30] A M Y Lin Y H Ping G F Chang et al ldquoNeuroprotectiveeffect of oral SB remedy (Scutellaria baicalensis Georgi andBupleurum scorzonerifolfium Willd) on iron-induced neuro-degeneration in the nigrostriatal dopaminergic system of ratbrainrdquo Journal of Ethnopharmacology vol 134 no 3pp 884ndash891 2011
[31] S Y Yoon I C dela Pena C Y Shin et al ldquoConvulsion-related activities of Scutellaria flavones are related to the 57-dihydroxyl structuresrdquo European Journal of Pharmacologyvol 659 no 2-3 pp 155ndash160 2011
[32] L Chen J Dou Z Su et al ldquoSynergistic activity of baicaleinwith ribavirin against influenza A (H1N1) virus infections incell culture and in micerdquo Antiviral Research vol 91 no 3pp 314ndash320 2011
[33] M Li-Weber ldquoNew therapeutic aspects of flavones the anti-cancer properties of Scutellaria and its main active constitu-ents wogonin baicalein and baicalinrdquo Cancer TreatmentReviews vol 35 no 1 pp 57ndash68 2009
[34] D E Shieh L T Liu and C C Lin ldquoAntioxidant and free rad-ical scavenging effects of baicalein baicalin and wogoninrdquoAnticancer Research vol 20 no 5A pp 2861ndash2865 2000
[35] B Bandyopadhyay and S K Bandyopadhyay ldquoProtectiveeffect of zinc gluconate on chemically induced gastric ulcerrdquoThe Indian Journal of Medical Research vol 106 pp 27ndash321997
[36] S S Poulsen ldquoOn the role of epidermal growth factor in thedefence of the gastroduodenal mucosardquo Scandinavian Journalof Gastroenterology vol 128 pp 20ndash23 1987
[37] S Kwiecień T Brzozowski P C H Konturek and S JKonturek ldquoThe role of reactive oxygen species in action ofnitric oxide-donors on stress-induced gastric mucosal lesionsrdquoJournal of Physiology and Pharmacology vol 53 4 Part 2pp 761ndash773 2002
[38] I Chattopadhyay U Bandyopadhyay K Biswas P Maity andR K Banerjee ldquoIndomethacin inactivates gastric peroxidase toinduce reactive-oxygen-mediated gastric mucosal injury andcurcumin protects it by preventing peroxidase inactivationand scavenging reactive oxygenrdquo Free Radical Biology amp Med-icine vol 40 no 8 pp 1397ndash1408 2006
[39] M Maes P Ruckoanich Y S Chang N Mahanonda andM Berk ldquoMultiple aberrations in shared inflammatory andoxidative amp nitrosative stress (IOampNS) pathways explain theco-association of depression and cardiovascular disorder(CVD) and the increased risk for CVD and due mortality indepressed patientsrdquo Progress in Neuro-Psychopharmacologyand Biological Psychiatry vol 35 no 3 pp 769ndash783 2011
Computational and Mathematical Methods in Medicine
Hindawiwwwhindawicom Volume 2018
Behavioural Neurology
OphthalmologyJournal of
Hindawiwwwhindawicom Volume 2018
Diabetes ResearchJournal of
Hindawiwwwhindawicom Volume 2018
Hindawiwwwhindawicom Volume 2018
Research and TreatmentAIDS
Hindawiwwwhindawicom Volume 2018
Gastroenterology Research and Practice
Hindawiwwwhindawicom Volume 2018
Parkinsonrsquos Disease
Evidence-Based Complementary andAlternative Medicine
Volume 2018Hindawiwwwhindawicom
Submit your manuscripts atwwwhindawicom
interfere with the mucosal defense system and cause ulcerrecurrence with some ulcerogenic factors [22 23]
In recent years chemical drugs used for the treatmentof gastric ulcers have induced many side effects Recentlynewly developed drugs with herbal origins may offerreduced side effects compared with chemical drugs [24]
In folk knowledge medicinal plants have been used forthe treatment of various disorders More and more medic-inal plants with various therapeutic properties especially forthe treatment of gastritis and gastric ulcers have been identi-fied [25ndash27] However few traditional Chinese medicinalplants for gastric ulcer treatment have been studied Cur-rently because of the lack of effective and applicable pharma-cological treatments for gastric ulcer more and more peoplehave focused on traditional medicines The investigation ofthe therapeutic functions of traditional medicinal herbs ingastric ulcer offer promising potential
Scutellaria baicalensis is a popular medicinal herb used intraditional Chinese medicine and it is used for the treatmentof high fevers ulcers inflammation and even cancer Themain bioactive flavonoids in Scutellaria baicalensis includebaicalein baicalin (BA) (baicalein-7-glucuronide) wogoninwogonoside (wogonin-7-glucuronide) oroxylin A and orox-ylin A-7-glucuronide Scutellaria baicalensis and its flavoneshave been studied for their various pharmacological activi-ties including anti-inflammatory [28] antibacterial [29]neuroprotective [30] anticonvulsant [31] antiviral [32]antitumor [33] and antioxidant [34] activities BA is themostpopular bioactive flavonoid for treating ulcers However the
(a) (b) (c)
(d) (e) (f)
(g) (h)
Figure 3 Photomicrographs of acetic acid-induced gastric ulcers from different groups (a) sham group (b) HE staining of the model groupinduced by acetic acid (cndashe) HE staining of the BA-Zn group induced by acetic acid and treated daily with BA-Zn (325 65 and 13mgkgpo) (f) HE staining of the BA group induced by acetic acid and treated daily with BA (46mgkg po) (g) HE staining of the zinc-gluconategroup induced by acetic acid and treated daily with zinc-gluconate (932mgkg po) and (h) HE staining of the omeprazole group inducedby acetic acid and treated daily with omeprazole (40mgkg po) The HE stained slides were visualized under a bright field microscopewith 20x magnification
Table 2 Concentration of TNF-α and IL-8 in rat mucosa inducedby acetic acid
Omeprazole 4 132plusmn 009lowastlowastlowast 045plusmn 001lowastlowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
6 Gastroenterology Research and Practice
antichronic gastric ulcer effects of BA alone or in complexhave not yet been elucidated
In this paper we examined the effects of BA-Zn BA andzinc-gluconate and related mechanisms on gastric ulcer heal-ing in an acetic acid-induced gastric ulcer rat model It hasbeen reported that zinc-gluconate has a protective effect ongastric ulcers [35] Acetic acid induces a state of acute stressin the gastric mucosa subsequently inducing gastric ulcersMoreover acetic acid-induced gastric ulceration leads tochronic oxidative stress with decreased SOD activity andGSH-Px expression levels and increased lipid peroxidation(MDA) It is well known that SOD GSH-Px and MDA playimportant roles in protecting the gastric mucosa against var-ious damaging agents [36 37] GSH-Px also plays an impor-tant role in protecting against oxidative gastric mucosalinjury [38] MDA is currently regarded as a reliable indexof ROS-induced mucosal injury [39] Therefore the detec-tion of SOD GSH-Px and MDA contents can reflect andindicate the level of oxidative stress In addition increasedconcentrations of TNF-α and IL-8 were detected in the ulcer-ated gastric mucosa BA-Zn (13mgkg) significantly acceler-ated the healing of gastric ulcers through an increase in SODand GSH-Px activity and a decrease in MDA IL-8 and TNF-α contents We also detected the levels of SOD IL-8 andTNF-α by Western blot We found that BA-Zn significantlyaccelerated ulcer healing by decreasing oxidative stress andattenuating inflammation In our results zinc-gluconate alsohas a protective effect on gastric ulcers but BA-Zn has much
stronger protective and healing abilities in gastric ulcers Onthe basis of our data BA-Zn (13mgkg) has greater antigas-tric ulcer abilities than either BA or zinc-gluconate
Collectively BA-Zn presents important ulcer-healingproperties in the model of chronic ulcer induced by aceticacid in rats Omeprazole is one of the most popular drugsused for the therapeutic control of gastroduodenal ulcers inhumans In our work BA-Zn also exerted an antiulcerogeniceffect similar to that of omeprazole against the developmentof acetic acid-induced gastric ulcers in rats using antioxidantand anti-inflammatory abilities Therefore the BA-Zn com-plex may become a potential and promising drug for thetreatment of human gastroduodenal ulcers In summaryour study indicates that BA-Zn promotes ulcer healing bydecreasing oxidative stress and attenuating inflammation inan acetic acid-induced gastric ulcer rat model Howeveradditional studies are needed to explore the novel mecha-nisms of BA-Zn and determine whether other mechanismsare also involved in the antiulcer effects of this complex
5 Conclusion
In conclusion BA-Zn facilitates the healing of acetic-inducedchronic ulcers in rats through its antioxidant and anti-inflammatory properties The results of this study provide afoundation for the clinical application of BA-Zn in the treat-ment of gastroduodenal ulcers
SOD
IL-8
TNF-훼
훽-Actin
Sham Model BA O325
BA-Zn (mgkg)
Z1365
(a)
SOD25
2015100500
Sham
Mod
el BA 325 6
5
BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Sham
Mod
el BA 325 6
5BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Sham
Mod
el BA 325 6
5
BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Prot
ein
leve
l
20
15
10
05
00
Prot
ein
leve
l20
15
10
05
00
Prot
ein
leve
l
IL-8 TNF-훼
(b)
Figure 4 Western blot analysis of SOD TNF-α and IL-8 expression (a) The protein expression levels of SOD TNF-α and IL-8 wereanalyzed by Western blot analysis β-Actin was used as a loading control (b) Quantification of SOD TNF-α and IL-8 protein expressionlevels using ImageJ software Z zinc-gluconate O omeprazole lowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
7Gastroenterology Research and Practice
Data Availability
The data used to support the findings of this study are avail-able from the corresponding author upon request
Conflicts of Interest
The authors declare that there are no conflicts of interest andno financial conflicts regarding the publication of this paper
Authorsrsquo Contributions
This study was designed by Xu Liu Experimental work wasdone by Hui Yang Zhong-Kun Ren Yi Lu Xiao-Feng Zengand Ling Li The first draft of this paper was written by HuiYang and reviewed by Xu Liu and Rong-Ping ZhangZhong-Kun Ren and Yi Lu reviewed the methodology andresults All authors reviewed and approved the final version
Acknowledgments
The present study was supported by the Yunnan AppliedBasic Research Projects (Grant no 2005C00092)
References
[1] J L Goldstein J Aisenberg F Lanza et al ldquoA multicenterrandomized double-blind active-comparator placebo-con-trolled parallel-group comparison of the incidence of endo-scopic gastric and duodenal ulcer rates with valdecoxib ornaproxen in healthy subjects aged 65 to 75 yearsrdquo ClinicalTherapeutics vol 28 no 3 pp 340ndash351 2006
[2] G H Heeba M K A Hassan and R S Amin ldquoGastroprotec-tive effect of simvastatin against indomethacin-induced gastriculcer in rats role of nitric oxide and prostaglandinsrdquo EuropeanJournal of Pharmacology vol 607 no 1ndash3 pp 188ndash193 2009
[3] P A Gladding M W I Webster H B Farrell I S L ZengR Park and N Ruijne ldquoThe antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacody-namic interaction with aspirin in healthy volunteersrdquo TheAmerican Journal of Cardiology vol 101 no 7 pp 1060ndash1063 2008
[4] A Lanas M A Perez-Aisa F Feu et al ldquoA nationwide studyof mortality associated with hospital admission due to severegastrointestinal events and those associated with nonsteroidalantiinflammatory drug userdquo The American Journal of Gastro-enterology vol 100 no 8 pp 1685ndash1693 2005
[5] B Cryer and K W Mahaffey ldquoGastrointestinal ulcers role ofaspirin and clinical outcomes pathobiology diagnosis andtreatmentrdquo Journal of Multidisciplinary Healthcare vol 7pp 137ndash146 2014
[6] J Lu J S Wang and L Y Kong ldquoAnti-inflammatory effects ofHuang-Lian-Jie-Du decoction its two fractions and four typi-cal compoundsrdquo Journal of Ethnopharmacology vol 134no 3 pp 911ndash918 2011
[7] J M Hwang T H Tseng Y Y Tsai et al ldquoProtective effects ofbaicalein on tert-butyl hydroperoxide-induced hepatic toxicityin rat hepatocytesrdquo Journal of Biomedical Science vol 12no 2 pp 389ndash397 2005
[8] J Dou L Chen G Xu et al ldquoEffects of baicalein on Sendaivirus in vivo are linked to serum baicalin and its inhibition
of hemagglutinin-neuraminidaserdquo Archives of Virologyvol 156 no 5 pp 793ndash801 2011
[9] M Y Yun J H Yang D K Kim et al ldquoTherapeutic effects ofbaicalein on atopic dermatitis-like skin lesions of NCNgamice induced by Dermatophagoides pteronyssinusrdquo Interna-tional Immunopharmacology vol 10 no 9 pp 1142ndash11482010
[10] J H Liu H Wann M M Chen et al ldquoBaicalein signifi-cantly protects human retinal pigment epithelium cellsagainst H2O2-induced oxidative stress by scavenging reac-tive oxygen species and downregulating the expression ofmatrix metalloproteinase-9 and vascular endothelial growthfactorrdquo Journal of Ocular Pharmacology and Therapeuticsvol 26 no 5 pp 421ndash429 2010
[11] P D Zalewski A Q Truong-Tran D Grosser L JayaramC Murgia and R E Ruffin ldquoZinc metabolism in airway epi-thelium and airway inflammation basic mechanisms and clin-ical targets A reviewrdquo Pharmacology amp Therapeutics vol 105no 2 pp 127ndash149 2005
[12] M Odashima M Otaka M Jin et al ldquoZinc L-carnosine pro-tects colonic mucosal injury through induction of heat shockprotein 72 and suppression of NF-κB activationrdquo Life Sciencesvol 79 no 24 pp 2245ndash2250 2006
[13] A Bhattacharyya R Chattopadhyay S Mitra and S E CroweldquoOxidative stress an essential factor in the pathogenesis of gas-trointestinal mucosal diseasesrdquo Physiological Reviews vol 94no 2 pp 329ndash354 2014
[14] L Chanudom and J Tangpong ldquoAnti-inflammation propertyof Syzygium cumini (L) Skeels on indomethacin-inducedacute gastric ulcerationrdquo Gastroenterology Research and Prac-tice vol 2015 Article ID 343642 12 pages 2015
[15] L M da Silva A Allemand D A G B Mendes et al ldquoEtha-nolic extract of roots from Arctium lappa L accelerates thehealing of acetic acid-induced gastric ulcer in rats involve-ment of the antioxidant systemrdquo Food and Chemical Toxicol-ogy vol 51 pp 179ndash187 2013
[16] S K Jaiswal C V Rao B Sharma P Mishra S Das andM KDubey ldquoGastroprotective effect of standardized leaf extractfrom Argyreia speciosa on experimental gastric ulcers in ratsrdquoJournal of Ethnopharmacology vol 137 no 1 pp 341ndash3442011
[17] A A El-Fakhry M A El-Daker R I Badr et al ldquoAssociationof the CagA gene positive Helicobacter pylori and tissue levelsof interleukin-17 and interleukin-8 in gastric ulcer patientsrdquoThe Egyptian Journal of Immunology vol 19 no 1 pp 51ndash62 2012
[18] Y W Yin A M Hu Q Q Sun et al ldquoAssociation betweeninterleukin-8 gene minus251 TA polymorphism and the risk ofpeptic ulcer disease a meta-analysisrdquo Human Immunologyvol 74 no 1 pp 125ndash130 2013
[19] S Okabe J L A Roth and C J Pfeiffer ldquoA method for exper-imental penetrating gastric and duodenal ulcers in ratsObservations on normal healingrdquo The American Journal ofDigestive Diseases vol 16 no 3 pp 277ndash284 1971
[20] K Takagi S Okabe and R Saziki ldquoA newmethod for the pro-duction of chronic gastric ulcer in rats and the effect of severaldrugs on its healingrdquo Japanese Journal of Pharmacologyvol 19 no 3 pp 418ndash426 1969
[21] S Okabe and K Amagase ldquoAn overview of acetic acid ulcermodelsmdashthe history and state of the art of peptic ulcerresearchrdquo Biological amp Pharmaceutical Bulletin vol 28no 8 pp 1321ndash1341 2005
8 Gastroenterology Research and Practice
[22] A Tarnawski J Stachura W J Krause T G Douglass andH Gergely ldquoQuality of gastric ulcer healing a new emerg-ing conceptrdquo Journal of Clinical Gastroenterology vol 13Supplement 1 pp S42ndashS47 1991
[23] A S Tarnawski ldquoCellular and molecular mechanisms of gas-trointestinal ulcer healingrdquo Digestive Diseases and Sciencesvol 50 Supplement 1 pp S24ndashS33 2005
[24] M Arun and V V Asha ldquoGastroprotective effect of Dodonaeaviscosa on various experimental ulcer modelsrdquo Journal of Eth-nopharmacology vol 118 no 3 pp 460ndash465 2008
[25] A Alkofahi and A H Atta ldquoPharmacological screening of theanti-ulcerogenic effects of some Jordanian medicinal plants inratsrdquo Journal of Ethnopharmacology vol 67 no 3 pp 341ndash345 1999
[26] S Khennouf H Benabdallah K Gharzouli et al ldquoEffect oftannins from Quercus suber and Quercus coccifera leaves onethanol-induced gastric lesions in micerdquo Journal of Agricul-tural and Food Chemistry vol 51 no 5 pp 1469ndash1473 2003
[27] S Bhattacharya S R Chaudhuri S Chattopadhyay and S KBandyopadhyay ldquoHealing properties of some Indian medici-nal plants against indomethacin-induced gastric ulceration ofratsrdquo Journal of Clinical Biochemistry and Nutrition vol 41no 2 pp 106ndash114 2007
[28] B Q Li T Fu W H Gong et al ldquoThe flavonoid baicalinexhibits anti-inflammatory activity by binding to chemo-kinesrdquo Immunopharmacology vol 49 no 3 pp 295ndash3062000
[29] J Wu D Hu and K X Wang ldquoStudy of Scutellaria baicalensisand Baicalin against antimicrobial susceptibility of Helicobac-ter pylori strains in vitrordquo Zhong yao cai = Zhongyaocai = Jour-nal of Chinese Medicinal Materials vol 31 no 5 pp 707ndash7102008
[30] A M Y Lin Y H Ping G F Chang et al ldquoNeuroprotectiveeffect of oral SB remedy (Scutellaria baicalensis Georgi andBupleurum scorzonerifolfium Willd) on iron-induced neuro-degeneration in the nigrostriatal dopaminergic system of ratbrainrdquo Journal of Ethnopharmacology vol 134 no 3pp 884ndash891 2011
[31] S Y Yoon I C dela Pena C Y Shin et al ldquoConvulsion-related activities of Scutellaria flavones are related to the 57-dihydroxyl structuresrdquo European Journal of Pharmacologyvol 659 no 2-3 pp 155ndash160 2011
[32] L Chen J Dou Z Su et al ldquoSynergistic activity of baicaleinwith ribavirin against influenza A (H1N1) virus infections incell culture and in micerdquo Antiviral Research vol 91 no 3pp 314ndash320 2011
[33] M Li-Weber ldquoNew therapeutic aspects of flavones the anti-cancer properties of Scutellaria and its main active constitu-ents wogonin baicalein and baicalinrdquo Cancer TreatmentReviews vol 35 no 1 pp 57ndash68 2009
[34] D E Shieh L T Liu and C C Lin ldquoAntioxidant and free rad-ical scavenging effects of baicalein baicalin and wogoninrdquoAnticancer Research vol 20 no 5A pp 2861ndash2865 2000
[35] B Bandyopadhyay and S K Bandyopadhyay ldquoProtectiveeffect of zinc gluconate on chemically induced gastric ulcerrdquoThe Indian Journal of Medical Research vol 106 pp 27ndash321997
[36] S S Poulsen ldquoOn the role of epidermal growth factor in thedefence of the gastroduodenal mucosardquo Scandinavian Journalof Gastroenterology vol 128 pp 20ndash23 1987
[37] S Kwiecień T Brzozowski P C H Konturek and S JKonturek ldquoThe role of reactive oxygen species in action ofnitric oxide-donors on stress-induced gastric mucosal lesionsrdquoJournal of Physiology and Pharmacology vol 53 4 Part 2pp 761ndash773 2002
[38] I Chattopadhyay U Bandyopadhyay K Biswas P Maity andR K Banerjee ldquoIndomethacin inactivates gastric peroxidase toinduce reactive-oxygen-mediated gastric mucosal injury andcurcumin protects it by preventing peroxidase inactivationand scavenging reactive oxygenrdquo Free Radical Biology amp Med-icine vol 40 no 8 pp 1397ndash1408 2006
[39] M Maes P Ruckoanich Y S Chang N Mahanonda andM Berk ldquoMultiple aberrations in shared inflammatory andoxidative amp nitrosative stress (IOampNS) pathways explain theco-association of depression and cardiovascular disorder(CVD) and the increased risk for CVD and due mortality indepressed patientsrdquo Progress in Neuro-Psychopharmacologyand Biological Psychiatry vol 35 no 3 pp 769ndash783 2011
Computational and Mathematical Methods in Medicine
Hindawiwwwhindawicom Volume 2018
Behavioural Neurology
OphthalmologyJournal of
Hindawiwwwhindawicom Volume 2018
Diabetes ResearchJournal of
Hindawiwwwhindawicom Volume 2018
Hindawiwwwhindawicom Volume 2018
Research and TreatmentAIDS
Hindawiwwwhindawicom Volume 2018
Gastroenterology Research and Practice
Hindawiwwwhindawicom Volume 2018
Parkinsonrsquos Disease
Evidence-Based Complementary andAlternative Medicine
Volume 2018Hindawiwwwhindawicom
Submit your manuscripts atwwwhindawicom
antichronic gastric ulcer effects of BA alone or in complexhave not yet been elucidated
In this paper we examined the effects of BA-Zn BA andzinc-gluconate and related mechanisms on gastric ulcer heal-ing in an acetic acid-induced gastric ulcer rat model It hasbeen reported that zinc-gluconate has a protective effect ongastric ulcers [35] Acetic acid induces a state of acute stressin the gastric mucosa subsequently inducing gastric ulcersMoreover acetic acid-induced gastric ulceration leads tochronic oxidative stress with decreased SOD activity andGSH-Px expression levels and increased lipid peroxidation(MDA) It is well known that SOD GSH-Px and MDA playimportant roles in protecting the gastric mucosa against var-ious damaging agents [36 37] GSH-Px also plays an impor-tant role in protecting against oxidative gastric mucosalinjury [38] MDA is currently regarded as a reliable indexof ROS-induced mucosal injury [39] Therefore the detec-tion of SOD GSH-Px and MDA contents can reflect andindicate the level of oxidative stress In addition increasedconcentrations of TNF-α and IL-8 were detected in the ulcer-ated gastric mucosa BA-Zn (13mgkg) significantly acceler-ated the healing of gastric ulcers through an increase in SODand GSH-Px activity and a decrease in MDA IL-8 and TNF-α contents We also detected the levels of SOD IL-8 andTNF-α by Western blot We found that BA-Zn significantlyaccelerated ulcer healing by decreasing oxidative stress andattenuating inflammation In our results zinc-gluconate alsohas a protective effect on gastric ulcers but BA-Zn has much
stronger protective and healing abilities in gastric ulcers Onthe basis of our data BA-Zn (13mgkg) has greater antigas-tric ulcer abilities than either BA or zinc-gluconate
Collectively BA-Zn presents important ulcer-healingproperties in the model of chronic ulcer induced by aceticacid in rats Omeprazole is one of the most popular drugsused for the therapeutic control of gastroduodenal ulcers inhumans In our work BA-Zn also exerted an antiulcerogeniceffect similar to that of omeprazole against the developmentof acetic acid-induced gastric ulcers in rats using antioxidantand anti-inflammatory abilities Therefore the BA-Zn com-plex may become a potential and promising drug for thetreatment of human gastroduodenal ulcers In summaryour study indicates that BA-Zn promotes ulcer healing bydecreasing oxidative stress and attenuating inflammation inan acetic acid-induced gastric ulcer rat model Howeveradditional studies are needed to explore the novel mecha-nisms of BA-Zn and determine whether other mechanismsare also involved in the antiulcer effects of this complex
5 Conclusion
In conclusion BA-Zn facilitates the healing of acetic-inducedchronic ulcers in rats through its antioxidant and anti-inflammatory properties The results of this study provide afoundation for the clinical application of BA-Zn in the treat-ment of gastroduodenal ulcers
SOD
IL-8
TNF-훼
훽-Actin
Sham Model BA O325
BA-Zn (mgkg)
Z1365
(a)
SOD25
2015100500
Sham
Mod
el BA 325 6
5
BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Sham
Mod
el BA 325 6
5BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Sham
Mod
el BA 325 6
5
BA-Zn (mgkg)
13
Om
epra
zole
Zinc
-glu
cona
te
Prot
ein
leve
l
20
15
10
05
00
Prot
ein
leve
l20
15
10
05
00
Prot
ein
leve
l
IL-8 TNF-훼
(b)
Figure 4 Western blot analysis of SOD TNF-α and IL-8 expression (a) The protein expression levels of SOD TNF-α and IL-8 wereanalyzed by Western blot analysis β-Actin was used as a loading control (b) Quantification of SOD TNF-α and IL-8 protein expressionlevels using ImageJ software Z zinc-gluconate O omeprazole lowastP lt 0 05 lowastlowastP lt 0 01 and lowastlowastlowastP lt 0 001 vs the model group
7Gastroenterology Research and Practice
Data Availability
The data used to support the findings of this study are avail-able from the corresponding author upon request
Conflicts of Interest
The authors declare that there are no conflicts of interest andno financial conflicts regarding the publication of this paper
Authorsrsquo Contributions
This study was designed by Xu Liu Experimental work wasdone by Hui Yang Zhong-Kun Ren Yi Lu Xiao-Feng Zengand Ling Li The first draft of this paper was written by HuiYang and reviewed by Xu Liu and Rong-Ping ZhangZhong-Kun Ren and Yi Lu reviewed the methodology andresults All authors reviewed and approved the final version
Acknowledgments
The present study was supported by the Yunnan AppliedBasic Research Projects (Grant no 2005C00092)
References
[1] J L Goldstein J Aisenberg F Lanza et al ldquoA multicenterrandomized double-blind active-comparator placebo-con-trolled parallel-group comparison of the incidence of endo-scopic gastric and duodenal ulcer rates with valdecoxib ornaproxen in healthy subjects aged 65 to 75 yearsrdquo ClinicalTherapeutics vol 28 no 3 pp 340ndash351 2006
[2] G H Heeba M K A Hassan and R S Amin ldquoGastroprotec-tive effect of simvastatin against indomethacin-induced gastriculcer in rats role of nitric oxide and prostaglandinsrdquo EuropeanJournal of Pharmacology vol 607 no 1ndash3 pp 188ndash193 2009
[3] P A Gladding M W I Webster H B Farrell I S L ZengR Park and N Ruijne ldquoThe antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacody-namic interaction with aspirin in healthy volunteersrdquo TheAmerican Journal of Cardiology vol 101 no 7 pp 1060ndash1063 2008
[4] A Lanas M A Perez-Aisa F Feu et al ldquoA nationwide studyof mortality associated with hospital admission due to severegastrointestinal events and those associated with nonsteroidalantiinflammatory drug userdquo The American Journal of Gastro-enterology vol 100 no 8 pp 1685ndash1693 2005
[5] B Cryer and K W Mahaffey ldquoGastrointestinal ulcers role ofaspirin and clinical outcomes pathobiology diagnosis andtreatmentrdquo Journal of Multidisciplinary Healthcare vol 7pp 137ndash146 2014
[6] J Lu J S Wang and L Y Kong ldquoAnti-inflammatory effects ofHuang-Lian-Jie-Du decoction its two fractions and four typi-cal compoundsrdquo Journal of Ethnopharmacology vol 134no 3 pp 911ndash918 2011
[7] J M Hwang T H Tseng Y Y Tsai et al ldquoProtective effects ofbaicalein on tert-butyl hydroperoxide-induced hepatic toxicityin rat hepatocytesrdquo Journal of Biomedical Science vol 12no 2 pp 389ndash397 2005
[8] J Dou L Chen G Xu et al ldquoEffects of baicalein on Sendaivirus in vivo are linked to serum baicalin and its inhibition
of hemagglutinin-neuraminidaserdquo Archives of Virologyvol 156 no 5 pp 793ndash801 2011
[9] M Y Yun J H Yang D K Kim et al ldquoTherapeutic effects ofbaicalein on atopic dermatitis-like skin lesions of NCNgamice induced by Dermatophagoides pteronyssinusrdquo Interna-tional Immunopharmacology vol 10 no 9 pp 1142ndash11482010
[10] J H Liu H Wann M M Chen et al ldquoBaicalein signifi-cantly protects human retinal pigment epithelium cellsagainst H2O2-induced oxidative stress by scavenging reac-tive oxygen species and downregulating the expression ofmatrix metalloproteinase-9 and vascular endothelial growthfactorrdquo Journal of Ocular Pharmacology and Therapeuticsvol 26 no 5 pp 421ndash429 2010
[11] P D Zalewski A Q Truong-Tran D Grosser L JayaramC Murgia and R E Ruffin ldquoZinc metabolism in airway epi-thelium and airway inflammation basic mechanisms and clin-ical targets A reviewrdquo Pharmacology amp Therapeutics vol 105no 2 pp 127ndash149 2005
[12] M Odashima M Otaka M Jin et al ldquoZinc L-carnosine pro-tects colonic mucosal injury through induction of heat shockprotein 72 and suppression of NF-κB activationrdquo Life Sciencesvol 79 no 24 pp 2245ndash2250 2006
[13] A Bhattacharyya R Chattopadhyay S Mitra and S E CroweldquoOxidative stress an essential factor in the pathogenesis of gas-trointestinal mucosal diseasesrdquo Physiological Reviews vol 94no 2 pp 329ndash354 2014
[14] L Chanudom and J Tangpong ldquoAnti-inflammation propertyof Syzygium cumini (L) Skeels on indomethacin-inducedacute gastric ulcerationrdquo Gastroenterology Research and Prac-tice vol 2015 Article ID 343642 12 pages 2015
[15] L M da Silva A Allemand D A G B Mendes et al ldquoEtha-nolic extract of roots from Arctium lappa L accelerates thehealing of acetic acid-induced gastric ulcer in rats involve-ment of the antioxidant systemrdquo Food and Chemical Toxicol-ogy vol 51 pp 179ndash187 2013
[16] S K Jaiswal C V Rao B Sharma P Mishra S Das andM KDubey ldquoGastroprotective effect of standardized leaf extractfrom Argyreia speciosa on experimental gastric ulcers in ratsrdquoJournal of Ethnopharmacology vol 137 no 1 pp 341ndash3442011
[17] A A El-Fakhry M A El-Daker R I Badr et al ldquoAssociationof the CagA gene positive Helicobacter pylori and tissue levelsof interleukin-17 and interleukin-8 in gastric ulcer patientsrdquoThe Egyptian Journal of Immunology vol 19 no 1 pp 51ndash62 2012
[18] Y W Yin A M Hu Q Q Sun et al ldquoAssociation betweeninterleukin-8 gene minus251 TA polymorphism and the risk ofpeptic ulcer disease a meta-analysisrdquo Human Immunologyvol 74 no 1 pp 125ndash130 2013
[19] S Okabe J L A Roth and C J Pfeiffer ldquoA method for exper-imental penetrating gastric and duodenal ulcers in ratsObservations on normal healingrdquo The American Journal ofDigestive Diseases vol 16 no 3 pp 277ndash284 1971
[20] K Takagi S Okabe and R Saziki ldquoA newmethod for the pro-duction of chronic gastric ulcer in rats and the effect of severaldrugs on its healingrdquo Japanese Journal of Pharmacologyvol 19 no 3 pp 418ndash426 1969
[21] S Okabe and K Amagase ldquoAn overview of acetic acid ulcermodelsmdashthe history and state of the art of peptic ulcerresearchrdquo Biological amp Pharmaceutical Bulletin vol 28no 8 pp 1321ndash1341 2005
8 Gastroenterology Research and Practice
[22] A Tarnawski J Stachura W J Krause T G Douglass andH Gergely ldquoQuality of gastric ulcer healing a new emerg-ing conceptrdquo Journal of Clinical Gastroenterology vol 13Supplement 1 pp S42ndashS47 1991
[23] A S Tarnawski ldquoCellular and molecular mechanisms of gas-trointestinal ulcer healingrdquo Digestive Diseases and Sciencesvol 50 Supplement 1 pp S24ndashS33 2005
[24] M Arun and V V Asha ldquoGastroprotective effect of Dodonaeaviscosa on various experimental ulcer modelsrdquo Journal of Eth-nopharmacology vol 118 no 3 pp 460ndash465 2008
[25] A Alkofahi and A H Atta ldquoPharmacological screening of theanti-ulcerogenic effects of some Jordanian medicinal plants inratsrdquo Journal of Ethnopharmacology vol 67 no 3 pp 341ndash345 1999
[26] S Khennouf H Benabdallah K Gharzouli et al ldquoEffect oftannins from Quercus suber and Quercus coccifera leaves onethanol-induced gastric lesions in micerdquo Journal of Agricul-tural and Food Chemistry vol 51 no 5 pp 1469ndash1473 2003
[27] S Bhattacharya S R Chaudhuri S Chattopadhyay and S KBandyopadhyay ldquoHealing properties of some Indian medici-nal plants against indomethacin-induced gastric ulceration ofratsrdquo Journal of Clinical Biochemistry and Nutrition vol 41no 2 pp 106ndash114 2007
[28] B Q Li T Fu W H Gong et al ldquoThe flavonoid baicalinexhibits anti-inflammatory activity by binding to chemo-kinesrdquo Immunopharmacology vol 49 no 3 pp 295ndash3062000
[29] J Wu D Hu and K X Wang ldquoStudy of Scutellaria baicalensisand Baicalin against antimicrobial susceptibility of Helicobac-ter pylori strains in vitrordquo Zhong yao cai = Zhongyaocai = Jour-nal of Chinese Medicinal Materials vol 31 no 5 pp 707ndash7102008
[30] A M Y Lin Y H Ping G F Chang et al ldquoNeuroprotectiveeffect of oral SB remedy (Scutellaria baicalensis Georgi andBupleurum scorzonerifolfium Willd) on iron-induced neuro-degeneration in the nigrostriatal dopaminergic system of ratbrainrdquo Journal of Ethnopharmacology vol 134 no 3pp 884ndash891 2011
[31] S Y Yoon I C dela Pena C Y Shin et al ldquoConvulsion-related activities of Scutellaria flavones are related to the 57-dihydroxyl structuresrdquo European Journal of Pharmacologyvol 659 no 2-3 pp 155ndash160 2011
[32] L Chen J Dou Z Su et al ldquoSynergistic activity of baicaleinwith ribavirin against influenza A (H1N1) virus infections incell culture and in micerdquo Antiviral Research vol 91 no 3pp 314ndash320 2011
[33] M Li-Weber ldquoNew therapeutic aspects of flavones the anti-cancer properties of Scutellaria and its main active constitu-ents wogonin baicalein and baicalinrdquo Cancer TreatmentReviews vol 35 no 1 pp 57ndash68 2009
[34] D E Shieh L T Liu and C C Lin ldquoAntioxidant and free rad-ical scavenging effects of baicalein baicalin and wogoninrdquoAnticancer Research vol 20 no 5A pp 2861ndash2865 2000
[35] B Bandyopadhyay and S K Bandyopadhyay ldquoProtectiveeffect of zinc gluconate on chemically induced gastric ulcerrdquoThe Indian Journal of Medical Research vol 106 pp 27ndash321997
[36] S S Poulsen ldquoOn the role of epidermal growth factor in thedefence of the gastroduodenal mucosardquo Scandinavian Journalof Gastroenterology vol 128 pp 20ndash23 1987
[37] S Kwiecień T Brzozowski P C H Konturek and S JKonturek ldquoThe role of reactive oxygen species in action ofnitric oxide-donors on stress-induced gastric mucosal lesionsrdquoJournal of Physiology and Pharmacology vol 53 4 Part 2pp 761ndash773 2002
[38] I Chattopadhyay U Bandyopadhyay K Biswas P Maity andR K Banerjee ldquoIndomethacin inactivates gastric peroxidase toinduce reactive-oxygen-mediated gastric mucosal injury andcurcumin protects it by preventing peroxidase inactivationand scavenging reactive oxygenrdquo Free Radical Biology amp Med-icine vol 40 no 8 pp 1397ndash1408 2006
[39] M Maes P Ruckoanich Y S Chang N Mahanonda andM Berk ldquoMultiple aberrations in shared inflammatory andoxidative amp nitrosative stress (IOampNS) pathways explain theco-association of depression and cardiovascular disorder(CVD) and the increased risk for CVD and due mortality indepressed patientsrdquo Progress in Neuro-Psychopharmacologyand Biological Psychiatry vol 35 no 3 pp 769ndash783 2011
Computational and Mathematical Methods in Medicine
Hindawiwwwhindawicom Volume 2018
Behavioural Neurology
OphthalmologyJournal of
Hindawiwwwhindawicom Volume 2018
Diabetes ResearchJournal of
Hindawiwwwhindawicom Volume 2018
Hindawiwwwhindawicom Volume 2018
Research and TreatmentAIDS
Hindawiwwwhindawicom Volume 2018
Gastroenterology Research and Practice
Hindawiwwwhindawicom Volume 2018
Parkinsonrsquos Disease
Evidence-Based Complementary andAlternative Medicine
Volume 2018Hindawiwwwhindawicom
Submit your manuscripts atwwwhindawicom
Data Availability
The data used to support the findings of this study are avail-able from the corresponding author upon request
Conflicts of Interest
The authors declare that there are no conflicts of interest andno financial conflicts regarding the publication of this paper
Authorsrsquo Contributions
This study was designed by Xu Liu Experimental work wasdone by Hui Yang Zhong-Kun Ren Yi Lu Xiao-Feng Zengand Ling Li The first draft of this paper was written by HuiYang and reviewed by Xu Liu and Rong-Ping ZhangZhong-Kun Ren and Yi Lu reviewed the methodology andresults All authors reviewed and approved the final version
Acknowledgments
The present study was supported by the Yunnan AppliedBasic Research Projects (Grant no 2005C00092)
References
[1] J L Goldstein J Aisenberg F Lanza et al ldquoA multicenterrandomized double-blind active-comparator placebo-con-trolled parallel-group comparison of the incidence of endo-scopic gastric and duodenal ulcer rates with valdecoxib ornaproxen in healthy subjects aged 65 to 75 yearsrdquo ClinicalTherapeutics vol 28 no 3 pp 340ndash351 2006
[2] G H Heeba M K A Hassan and R S Amin ldquoGastroprotec-tive effect of simvastatin against indomethacin-induced gastriculcer in rats role of nitric oxide and prostaglandinsrdquo EuropeanJournal of Pharmacology vol 607 no 1ndash3 pp 188ndash193 2009
[3] P A Gladding M W I Webster H B Farrell I S L ZengR Park and N Ruijne ldquoThe antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacody-namic interaction with aspirin in healthy volunteersrdquo TheAmerican Journal of Cardiology vol 101 no 7 pp 1060ndash1063 2008
[4] A Lanas M A Perez-Aisa F Feu et al ldquoA nationwide studyof mortality associated with hospital admission due to severegastrointestinal events and those associated with nonsteroidalantiinflammatory drug userdquo The American Journal of Gastro-enterology vol 100 no 8 pp 1685ndash1693 2005
[5] B Cryer and K W Mahaffey ldquoGastrointestinal ulcers role ofaspirin and clinical outcomes pathobiology diagnosis andtreatmentrdquo Journal of Multidisciplinary Healthcare vol 7pp 137ndash146 2014
[6] J Lu J S Wang and L Y Kong ldquoAnti-inflammatory effects ofHuang-Lian-Jie-Du decoction its two fractions and four typi-cal compoundsrdquo Journal of Ethnopharmacology vol 134no 3 pp 911ndash918 2011
[7] J M Hwang T H Tseng Y Y Tsai et al ldquoProtective effects ofbaicalein on tert-butyl hydroperoxide-induced hepatic toxicityin rat hepatocytesrdquo Journal of Biomedical Science vol 12no 2 pp 389ndash397 2005
[8] J Dou L Chen G Xu et al ldquoEffects of baicalein on Sendaivirus in vivo are linked to serum baicalin and its inhibition
of hemagglutinin-neuraminidaserdquo Archives of Virologyvol 156 no 5 pp 793ndash801 2011
[9] M Y Yun J H Yang D K Kim et al ldquoTherapeutic effects ofbaicalein on atopic dermatitis-like skin lesions of NCNgamice induced by Dermatophagoides pteronyssinusrdquo Interna-tional Immunopharmacology vol 10 no 9 pp 1142ndash11482010
[10] J H Liu H Wann M M Chen et al ldquoBaicalein signifi-cantly protects human retinal pigment epithelium cellsagainst H2O2-induced oxidative stress by scavenging reac-tive oxygen species and downregulating the expression ofmatrix metalloproteinase-9 and vascular endothelial growthfactorrdquo Journal of Ocular Pharmacology and Therapeuticsvol 26 no 5 pp 421ndash429 2010
[11] P D Zalewski A Q Truong-Tran D Grosser L JayaramC Murgia and R E Ruffin ldquoZinc metabolism in airway epi-thelium and airway inflammation basic mechanisms and clin-ical targets A reviewrdquo Pharmacology amp Therapeutics vol 105no 2 pp 127ndash149 2005
[12] M Odashima M Otaka M Jin et al ldquoZinc L-carnosine pro-tects colonic mucosal injury through induction of heat shockprotein 72 and suppression of NF-κB activationrdquo Life Sciencesvol 79 no 24 pp 2245ndash2250 2006
[13] A Bhattacharyya R Chattopadhyay S Mitra and S E CroweldquoOxidative stress an essential factor in the pathogenesis of gas-trointestinal mucosal diseasesrdquo Physiological Reviews vol 94no 2 pp 329ndash354 2014
[14] L Chanudom and J Tangpong ldquoAnti-inflammation propertyof Syzygium cumini (L) Skeels on indomethacin-inducedacute gastric ulcerationrdquo Gastroenterology Research and Prac-tice vol 2015 Article ID 343642 12 pages 2015
[15] L M da Silva A Allemand D A G B Mendes et al ldquoEtha-nolic extract of roots from Arctium lappa L accelerates thehealing of acetic acid-induced gastric ulcer in rats involve-ment of the antioxidant systemrdquo Food and Chemical Toxicol-ogy vol 51 pp 179ndash187 2013
[16] S K Jaiswal C V Rao B Sharma P Mishra S Das andM KDubey ldquoGastroprotective effect of standardized leaf extractfrom Argyreia speciosa on experimental gastric ulcers in ratsrdquoJournal of Ethnopharmacology vol 137 no 1 pp 341ndash3442011
[17] A A El-Fakhry M A El-Daker R I Badr et al ldquoAssociationof the CagA gene positive Helicobacter pylori and tissue levelsof interleukin-17 and interleukin-8 in gastric ulcer patientsrdquoThe Egyptian Journal of Immunology vol 19 no 1 pp 51ndash62 2012
[18] Y W Yin A M Hu Q Q Sun et al ldquoAssociation betweeninterleukin-8 gene minus251 TA polymorphism and the risk ofpeptic ulcer disease a meta-analysisrdquo Human Immunologyvol 74 no 1 pp 125ndash130 2013
[19] S Okabe J L A Roth and C J Pfeiffer ldquoA method for exper-imental penetrating gastric and duodenal ulcers in ratsObservations on normal healingrdquo The American Journal ofDigestive Diseases vol 16 no 3 pp 277ndash284 1971
[20] K Takagi S Okabe and R Saziki ldquoA newmethod for the pro-duction of chronic gastric ulcer in rats and the effect of severaldrugs on its healingrdquo Japanese Journal of Pharmacologyvol 19 no 3 pp 418ndash426 1969
[21] S Okabe and K Amagase ldquoAn overview of acetic acid ulcermodelsmdashthe history and state of the art of peptic ulcerresearchrdquo Biological amp Pharmaceutical Bulletin vol 28no 8 pp 1321ndash1341 2005
8 Gastroenterology Research and Practice
[22] A Tarnawski J Stachura W J Krause T G Douglass andH Gergely ldquoQuality of gastric ulcer healing a new emerg-ing conceptrdquo Journal of Clinical Gastroenterology vol 13Supplement 1 pp S42ndashS47 1991
[23] A S Tarnawski ldquoCellular and molecular mechanisms of gas-trointestinal ulcer healingrdquo Digestive Diseases and Sciencesvol 50 Supplement 1 pp S24ndashS33 2005
[24] M Arun and V V Asha ldquoGastroprotective effect of Dodonaeaviscosa on various experimental ulcer modelsrdquo Journal of Eth-nopharmacology vol 118 no 3 pp 460ndash465 2008
[25] A Alkofahi and A H Atta ldquoPharmacological screening of theanti-ulcerogenic effects of some Jordanian medicinal plants inratsrdquo Journal of Ethnopharmacology vol 67 no 3 pp 341ndash345 1999
[26] S Khennouf H Benabdallah K Gharzouli et al ldquoEffect oftannins from Quercus suber and Quercus coccifera leaves onethanol-induced gastric lesions in micerdquo Journal of Agricul-tural and Food Chemistry vol 51 no 5 pp 1469ndash1473 2003
[27] S Bhattacharya S R Chaudhuri S Chattopadhyay and S KBandyopadhyay ldquoHealing properties of some Indian medici-nal plants against indomethacin-induced gastric ulceration ofratsrdquo Journal of Clinical Biochemistry and Nutrition vol 41no 2 pp 106ndash114 2007
[28] B Q Li T Fu W H Gong et al ldquoThe flavonoid baicalinexhibits anti-inflammatory activity by binding to chemo-kinesrdquo Immunopharmacology vol 49 no 3 pp 295ndash3062000
[29] J Wu D Hu and K X Wang ldquoStudy of Scutellaria baicalensisand Baicalin against antimicrobial susceptibility of Helicobac-ter pylori strains in vitrordquo Zhong yao cai = Zhongyaocai = Jour-nal of Chinese Medicinal Materials vol 31 no 5 pp 707ndash7102008
[30] A M Y Lin Y H Ping G F Chang et al ldquoNeuroprotectiveeffect of oral SB remedy (Scutellaria baicalensis Georgi andBupleurum scorzonerifolfium Willd) on iron-induced neuro-degeneration in the nigrostriatal dopaminergic system of ratbrainrdquo Journal of Ethnopharmacology vol 134 no 3pp 884ndash891 2011
[31] S Y Yoon I C dela Pena C Y Shin et al ldquoConvulsion-related activities of Scutellaria flavones are related to the 57-dihydroxyl structuresrdquo European Journal of Pharmacologyvol 659 no 2-3 pp 155ndash160 2011
[32] L Chen J Dou Z Su et al ldquoSynergistic activity of baicaleinwith ribavirin against influenza A (H1N1) virus infections incell culture and in micerdquo Antiviral Research vol 91 no 3pp 314ndash320 2011
[33] M Li-Weber ldquoNew therapeutic aspects of flavones the anti-cancer properties of Scutellaria and its main active constitu-ents wogonin baicalein and baicalinrdquo Cancer TreatmentReviews vol 35 no 1 pp 57ndash68 2009
[34] D E Shieh L T Liu and C C Lin ldquoAntioxidant and free rad-ical scavenging effects of baicalein baicalin and wogoninrdquoAnticancer Research vol 20 no 5A pp 2861ndash2865 2000
[35] B Bandyopadhyay and S K Bandyopadhyay ldquoProtectiveeffect of zinc gluconate on chemically induced gastric ulcerrdquoThe Indian Journal of Medical Research vol 106 pp 27ndash321997
[36] S S Poulsen ldquoOn the role of epidermal growth factor in thedefence of the gastroduodenal mucosardquo Scandinavian Journalof Gastroenterology vol 128 pp 20ndash23 1987
[37] S Kwiecień T Brzozowski P C H Konturek and S JKonturek ldquoThe role of reactive oxygen species in action ofnitric oxide-donors on stress-induced gastric mucosal lesionsrdquoJournal of Physiology and Pharmacology vol 53 4 Part 2pp 761ndash773 2002
[38] I Chattopadhyay U Bandyopadhyay K Biswas P Maity andR K Banerjee ldquoIndomethacin inactivates gastric peroxidase toinduce reactive-oxygen-mediated gastric mucosal injury andcurcumin protects it by preventing peroxidase inactivationand scavenging reactive oxygenrdquo Free Radical Biology amp Med-icine vol 40 no 8 pp 1397ndash1408 2006
[39] M Maes P Ruckoanich Y S Chang N Mahanonda andM Berk ldquoMultiple aberrations in shared inflammatory andoxidative amp nitrosative stress (IOampNS) pathways explain theco-association of depression and cardiovascular disorder(CVD) and the increased risk for CVD and due mortality indepressed patientsrdquo Progress in Neuro-Psychopharmacologyand Biological Psychiatry vol 35 no 3 pp 769ndash783 2011
Computational and Mathematical Methods in Medicine
Hindawiwwwhindawicom Volume 2018
Behavioural Neurology
OphthalmologyJournal of
Hindawiwwwhindawicom Volume 2018
Diabetes ResearchJournal of
Hindawiwwwhindawicom Volume 2018
Hindawiwwwhindawicom Volume 2018
Research and TreatmentAIDS
Hindawiwwwhindawicom Volume 2018
Gastroenterology Research and Practice
Hindawiwwwhindawicom Volume 2018
Parkinsonrsquos Disease
Evidence-Based Complementary andAlternative Medicine
Volume 2018Hindawiwwwhindawicom
Submit your manuscripts atwwwhindawicom
[22] A Tarnawski J Stachura W J Krause T G Douglass andH Gergely ldquoQuality of gastric ulcer healing a new emerg-ing conceptrdquo Journal of Clinical Gastroenterology vol 13Supplement 1 pp S42ndashS47 1991
[23] A S Tarnawski ldquoCellular and molecular mechanisms of gas-trointestinal ulcer healingrdquo Digestive Diseases and Sciencesvol 50 Supplement 1 pp S24ndashS33 2005
[24] M Arun and V V Asha ldquoGastroprotective effect of Dodonaeaviscosa on various experimental ulcer modelsrdquo Journal of Eth-nopharmacology vol 118 no 3 pp 460ndash465 2008
[25] A Alkofahi and A H Atta ldquoPharmacological screening of theanti-ulcerogenic effects of some Jordanian medicinal plants inratsrdquo Journal of Ethnopharmacology vol 67 no 3 pp 341ndash345 1999
[26] S Khennouf H Benabdallah K Gharzouli et al ldquoEffect oftannins from Quercus suber and Quercus coccifera leaves onethanol-induced gastric lesions in micerdquo Journal of Agricul-tural and Food Chemistry vol 51 no 5 pp 1469ndash1473 2003
[27] S Bhattacharya S R Chaudhuri S Chattopadhyay and S KBandyopadhyay ldquoHealing properties of some Indian medici-nal plants against indomethacin-induced gastric ulceration ofratsrdquo Journal of Clinical Biochemistry and Nutrition vol 41no 2 pp 106ndash114 2007
[28] B Q Li T Fu W H Gong et al ldquoThe flavonoid baicalinexhibits anti-inflammatory activity by binding to chemo-kinesrdquo Immunopharmacology vol 49 no 3 pp 295ndash3062000
[29] J Wu D Hu and K X Wang ldquoStudy of Scutellaria baicalensisand Baicalin against antimicrobial susceptibility of Helicobac-ter pylori strains in vitrordquo Zhong yao cai = Zhongyaocai = Jour-nal of Chinese Medicinal Materials vol 31 no 5 pp 707ndash7102008
[30] A M Y Lin Y H Ping G F Chang et al ldquoNeuroprotectiveeffect of oral SB remedy (Scutellaria baicalensis Georgi andBupleurum scorzonerifolfium Willd) on iron-induced neuro-degeneration in the nigrostriatal dopaminergic system of ratbrainrdquo Journal of Ethnopharmacology vol 134 no 3pp 884ndash891 2011
[31] S Y Yoon I C dela Pena C Y Shin et al ldquoConvulsion-related activities of Scutellaria flavones are related to the 57-dihydroxyl structuresrdquo European Journal of Pharmacologyvol 659 no 2-3 pp 155ndash160 2011
[32] L Chen J Dou Z Su et al ldquoSynergistic activity of baicaleinwith ribavirin against influenza A (H1N1) virus infections incell culture and in micerdquo Antiviral Research vol 91 no 3pp 314ndash320 2011
[33] M Li-Weber ldquoNew therapeutic aspects of flavones the anti-cancer properties of Scutellaria and its main active constitu-ents wogonin baicalein and baicalinrdquo Cancer TreatmentReviews vol 35 no 1 pp 57ndash68 2009
[34] D E Shieh L T Liu and C C Lin ldquoAntioxidant and free rad-ical scavenging effects of baicalein baicalin and wogoninrdquoAnticancer Research vol 20 no 5A pp 2861ndash2865 2000
[35] B Bandyopadhyay and S K Bandyopadhyay ldquoProtectiveeffect of zinc gluconate on chemically induced gastric ulcerrdquoThe Indian Journal of Medical Research vol 106 pp 27ndash321997
[36] S S Poulsen ldquoOn the role of epidermal growth factor in thedefence of the gastroduodenal mucosardquo Scandinavian Journalof Gastroenterology vol 128 pp 20ndash23 1987
[37] S Kwiecień T Brzozowski P C H Konturek and S JKonturek ldquoThe role of reactive oxygen species in action ofnitric oxide-donors on stress-induced gastric mucosal lesionsrdquoJournal of Physiology and Pharmacology vol 53 4 Part 2pp 761ndash773 2002
[38] I Chattopadhyay U Bandyopadhyay K Biswas P Maity andR K Banerjee ldquoIndomethacin inactivates gastric peroxidase toinduce reactive-oxygen-mediated gastric mucosal injury andcurcumin protects it by preventing peroxidase inactivationand scavenging reactive oxygenrdquo Free Radical Biology amp Med-icine vol 40 no 8 pp 1397ndash1408 2006
[39] M Maes P Ruckoanich Y S Chang N Mahanonda andM Berk ldquoMultiple aberrations in shared inflammatory andoxidative amp nitrosative stress (IOampNS) pathways explain theco-association of depression and cardiovascular disorder(CVD) and the increased risk for CVD and due mortality indepressed patientsrdquo Progress in Neuro-Psychopharmacologyand Biological Psychiatry vol 35 no 3 pp 769ndash783 2011
![Original Article Baicalin down regulates the expression of ... · pathway plays an important part in UC [1, 8, 9]. Baicalin and colitis 4064 Int J Clin Exp Med 2014;7(11):4063-4072](https://static.documents.pub/doc/80x56/6081244fc6b52b7ad1642933/original-article-baicalin-down-regulates-the-expression-of-pathway-plays-an.jpg)
