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Ancient HerbSuppresses Inflammation
By Vicki Brower
With the removal of Vioxx® from the market, and sales of other drugs in thisclass plummeting, scientists are working overtime to identify natural agents thatsafely block the underlying factors that give rise to inflammation in the body.
Researchers have focused their microscopes on the herb ^o^uif/// , whichworks to block a lethal pro-inflammatory enzyme called 5-lipoxygenase(5-LOX). Until now, only limited strategies have been available to fight theinsidious effects of 5-LOX, a potent contributor to inflammatory processesinvolved in diseases as diverse as cancer, atherosclerosis, arthritis, inflam-matory bowel disease, and asthma. > > >
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CONTROLLiNG THE iNFLAMMATORY CASCADE
Unlike NSAIDs, boswellia fights inflammation by blocking pro-intlammatory 5-LOX(5-lipoxygenase). 5-LOX is the first enzyme in the metabolic pathway leading to thesynthesis of leukotrienes, which are harmful inflammatory substances that scientistsbelieve may have a direct influence on a number of disease processes. Efforts to develop5-LOX inhibitors that target asthma and cancer' suggest that boswellia extract may wellhave applications in managing these and other disease conditions.
In addition to inhibiting 5-LOX and blocking the biosynthesis of harmful inflammatoryleukotrienes/ boswellic acids decrease the activity of another pro-inflammatory enzyme,HLE (human leukocyte elastase). HLE is associated with rheumatoid arthritis and respira-tory illnesses such as pulmonary emphysema, cystic fibrosis, chronic bronchitis, and acuterespiratory distress syndrome^~all of which are linked by inflammation. Significantly, bothleukotriene levels and HLE release are increased in many inflammatory diseases and allergicreactions. To date, the m/y anti-inflammatory compounds that have been found to inhibitboth HLE and 5-LOX are those derived from bcsweliia,''
Scientists revealed boswellia's mechanism of action in a study in 2005. They found thatboswellia works in part by altering the expression of tumor necrosis factor-alpha (TNF-a),which plays an important role in inflammation. While the body needs pro-inflammatory cyto-kines like TNF-(x to fight off acute infections, an excess of such cytokines promotes chronicinflammation. Applying boswellia to cells had the selective effect of decreasing the TNF-a-induced expression of cell adhesion and matrix metalloproteinase proteins, biochemicalsthat are related to harmful endothelial dysfunction, cancer metastasis, arthritis, and otherdisease processes.^
Boswellia Basics
For thousands ofyears, folk med-icine practitioners have used theherb boswellia [Boswellia serrata)to treat a wide range of conditionsthat we now know are caused byinflammation. This herbal extractis derived from gum resin secretedby the boswellia tree, part of a fam-ily of medicinal plants grown andused in India. Africa, China, and theMiddle East.
Fighting Inflammation byInhibiting LOX Enzymes
In the late 1970s, researchersdiscovered that boswellia producesnotable anti-inflammatory effectsthat are distinct from those producedby nonsteroidal anti-inflammatorydrugs (NSAIDs) such as ibuprofenand aspirin.
NSAIDs quell inflammationprimarily by inhibiting the cyclo-oxygenase-2 (COX-2) enzyme.'Unfortunately, NSAIDs also blockthe COX-1 enzyme, which is neededto maintain a healthy stomach lining.
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While NSAIDs are partially effectivein treating pain and inflammation,side effects such as stomach irrita-tion and bleeding, kidney toxicity,and peptic ulcers make them lessappealing for long-term use. A pri-mary cause of NSAID toxicity is over-inhibition of the COX-1 enzyme.
The stomach-damaging proper-ties of NSAIDs appeared to be solvedin 1999, with the approval of selectiveCOX-2 inhibitors that demonstratedless stomach toxicity than NSAIDs.As early as luly 2000, however, LifeExtension alerted its members tothe risks associated with selective
COX-2 inhibitors. Since then, reportsabout the potentially dangerous car-diac side effects of COX-2 inhibitors-have led scientists to intensify thesearch for safer options.
Potential Uses in Preventing andManaging Cancer
Boswellia shows great prom-ise in the prevention and manage-ment of several forms of cancer.Pharmaceutical companies arenow testing drugs that inhibit LOXenzymes, for use as potential cancertherapeutics.'
German scientists have dem-onstrated that boswellia extractis a more potent inhibitor of theenzymes that encourage cancergrowth in humans than are certainchemotherapy drugs." Based onthese positive results with boswellia,the researchers believe that theplant's extracts may help prevent thedevelopment and spread of cancer.
Other researchers have testedboswellia extract against five differ-ent types of human leukemia cellsand two types of human hrain can-cer cells. They found that boswelliainhibited the proliferation of thesecancerous cells by prompting themto self-destruct. Stronger potenciesof boswellia were more effective inpromoting cancer cell death, thusdemonstrating a dose-dependenteffect. The Swiss researchers con-ducting this trial suggested thatboswellia may be able to prevent ortreat these cancers.'
Scientists from the ClevelandClinic found that an extract ofboswellia was effective against
human meningioma cells, whichare typically benign tumors of thebrain's covering. Boswellia worked bydecreasing the cells' ability to spreadand by killing the tumor cells."
Boswellia has also attracted theattention of prostate cancer research-ers. Prostate cancer cells sampledfrom men with the disease displayan abundance of the 5-LOX enzyme.''Other research has found that agentsthat inhibit the 5-LOX enzyme killhuman prostate cancer cells,'" sug-gesting that 5-LOX inhibitors suchas boswellia may have applicationsin preventing or arresting the growthof prostate cancer.**'"
Boswellia extracts also demon-strate promise in fighting melanoma,the deadliest form of skin cancer.Using advanced microscopy andcell-tracking techniques, scientistswere able to observe how boswelliaextracts caused melanoma cells todifferentiate in a healthy way and toadopt cell-growth patterns resem-bling those of normal cells, whilebecoming less able to metastasize.Using these techniques, they alsoobserved that boswellia causedfibrosarcoma (connective tissuecancer) cells to lose their ability tometastasize, and then induced cellu-lar suicide (apoptosis) in these samecells." At this point, there is enoughevidence to encourage researchersto continue looking for therapeutictreatment options utilizing boswelliain some of the most serious diseases.
Reducing Inflammation to LowerAtherosclerosis Risk
Inflammation is an importantcontributor to atherosclerosis andthe development of heart disease.Using boswellia to inhibit the 5-LOXenzymes and reduce inflammationmay prove to be an important ele-ment in preventing and treatingatherosclerosis.
Genetic research recentlyrevealed an intriguing correlationbetween 5-LOX and atherosclero-sis. Scientists discovered that micewith a genetic defect that resultedin their having only one copy of the5-LOX gene (rather than the usual
two copies) were completely protectedfrom developing atherosclerosis.'-
Researchers believe that 5-LOXcontributes to atherosclerosis in sev-eral ways. As noted earlier, increasesin the 5-LOX enzyme result in excessleukotriene products that chemicallyattract white blood cells to adhere tothe arterial walls. Furthermore, leu- ^kotrienes may promote vascular per- |meability and low-density lipoprotein g(LDL) oxidation. These combined |effects may promote the develop- fe'ment of atherosclerotic plaques in 9the arteries, a known risk factor for gheart attacks.'^
Using boswellia extract to inhibit5-LOX-induced leukotriene pro-duction could thus represent aneffective strategy to prevent or treatatherosclerosis.'^
Boswellia ImprovesSymptoms of Arthritis
Osteoarthritis and rheumatoidarthritis can cause disabling pain andimmobility in aging adults. Boswelliamay offer relief for arthritis suffersbecause of its well-known analgesic,anti-arthritic, and anti-inflammatoryproperties.
Osteoarthritis, the "wear and tear"arthritis, is caused by deteriorationof the cartilage that cushions joints.Research suggests that boswelliahelps prevent the deterioration ofcartilage and joint tissue. Scientistsnow theorize that boswellia maywork by inhibiting the breakdown ofconnective tissues that is caused bytumor necrosis factor-alpha (TNF~a)-induced expression of matrix metal-loproteinase enzymes}^
A pre-clinical animal study dem-onstrated boswellia's benefits in man-aging osteoarthritis. Dogs sufferingfrom osteoarthritis received boswelliaextract once daily for six weeks. Afteronly two weeks of therapy, 71% of theanimals showed significant improve-ments in clinical symptoms of arthri-tis, including reduced pain, stiffness,and lameness.'^
In a human study, boswellia wassimilarly shown to be effective inadults with osteoarthritis. Thirty sub-jects with osteoarthritis of the knee
Scientists now know that chronic inflam-mation underlies many of the diseasesthat afflict aging adults. Because mostanti-inflammatorv drugs work by inhibit-ing the COX enzymes, researchers havesought other means to quell disease-pro-voking inflammation.One of the most promising anti-inflamma-tory agents today comes from boswellia.a traditional herbal remedy long used tomanage conditions such as joint painand gastrointestinal irritation. Modernresearch confirms boswellia's novelinflammation-fighting effects. Boswelliaworks differently from most conventionalanti-inflammatory agents by inhibitinglipoxygenase (LOX) enzymes that arepowerful contributors to inflammationand disease.Boswellia is particularly effective ininhibiting 5-lipoxygenase (5-LOX), whichpromotes disease in part by contributingto the formation of damaging leuko-trienes. Leukotrienes promote asthma,cancer, and other disease processes.Through its action in blocking 5-LOX.boswellia demonstrates effects that mayhelp combat cancer, atherosclerosis,and asthma. Clinical studies reveal thatboswellia also relieves the symptoms anddiscomfort of arthritis and inflammatorybowel disease.An advanced boswellia formulation called5-LOXIN® displays particular efficacy ininhibiting 5-LOX's dangerous inflamma-tory effects.
took part in a 16-week, random-ized, double-blind, placebo-con-trolled trial. All of those who took aboswellia supplement reported lesspain and swelling, increased kneeflexion, and the ability to walk agreater distance.''"
Rheumatoid arthritis is classi-fied as an autoimmune disorder, inwhich the body attacks its own tis-sues as though they were foreigninvaders. Boswellia may also offerrelief of autoimmune-related rheu-matoid arthritis. Boswellia can helpreduce immune cells that encourageinflammation while increasing thenumber of immune cells that inhibitinflammation.'" Studies indicate thatboswellia's ability to modulate theimmune system and inhibit inflam-matory activity may help improve thesymptoms of rheumatoid arthritisand other autoimmune conditions.''
Critical Support AgainstInflammatory Bowel Diseases
Ulcerative colitis and Crohn'sdisease are known as inflammatorybowel diseases. Ulcerative colitisprimarily affects the colon, while(John's disease may affect the entiregastrointestinal tract. These auto-immune conditions are marked bysymptoms such as severe gastroin-testinal pain and cramping, diarrhea,fatigue, weight loss, and malnutrition.Boswellia may offer much-neededsupport for people facing these chal-lenging conditions.
A recent survey of Germanpatients with inflammatory boweldisease showed that over one thirdused complementary and alternativemedicines—such as herbal therapies,homeopathy, probiotics, or acupunc-ture—to help manage their condition.Those who used boswellia extract,however, reported better results thanthose using other approaches.'"
Researchers recently testedboswellia extract in animals withexperimentally induced inflamma-tory bowel disease. The animals dem-onstrated tissue injui y and adherenceof white blood cells to the gastro-intestinal lining. Wiien the animalsreceived boswellia extract, however,they exhibited less inflammationand destruction of gastrointestinaltissue. These benefits contributedto a reduction in the symptoms ofinflammatory bowel disease."*
Other researchers tested boswelliaextract in an animal model of ulcer-ative colitis to assess its mechanismof action and compare its efficacywith a steroid commonly used totreat the disease in humans. " Theyfound that the boswellia extractprotected the colon by significantlyreduchig disease activity, as mea-sured by decreased recruitmentand adherence of white blood cellsas well as platelets in the inflamedcolon. They also discovered thatboswellia decreased the presenceof a biochemical known as P-selec-tin that plays a role in active colitis.Boswellia's impressive protective
effects were similar to those seen inpatients receiving steroids to reducetheir symptoms of colitis.
Boswellia shows important treat-ment activity against ulcerative coli-tis. In a clinical trial of 30 ulcerativecolitis patients, 20 patients took aconventional boswellia extract threetimes daily for six weeks, while 10
AN ADVANCED BOSWELLIAFORMULATION: 5-LOXIN®
While the anti-inflammatory effects ofboswellia are well documenfed, differentpreparations of the herb vary greatly intheir pofency and biochemical makeup.
Scienfisfs avidly sfudied boswellia todetermine how it fights the inflammation-provoking 5-lipoxygenase (5-LOX) enzyme.They discovered a compound known asAKBA (3-0-acetyl-ll-keto-B-boswellicacid), which binds directly to 5-LOX andinhibits its activity.-*^ Other boswellia-derived compounds only partially andincompletely inhibit 5-LOX." -
Researchers have long sought anAKBA-rich boswellia extract for the treat-ment of chronic inflammatory disorders.Even in standardized boswellia extracts,however, biologically active AKBA makesup only a small fraction of the totalcomposition.
Several years ago, researchers dis-covered how to produce a standardizedboswellia formulation that contains aconcentration of AKBA greater than 30%.This product was patented and trade-marked underthe name 5-LOXiN^ Testingfound that 5-LOXir inhibits 5-LOX evenmore effectively than the highest-qualityboswellia formulation.
In an animal study comparing theefficacy of 5-LOXIN*^to that of the popu-lar anti-inflammatory drug ibuprofen.5-LOXIN® produced a 27% reductionin inflammation, compared to 35% foribuprofen.^ Another study comparing5-LOXIN® to the anti-inflammatorysteroid drug prednisone found thatS-LOXIN" ' produced a 55% reduction ininflammation, similar to the effects ofprednisone.'-^^^ 5-LOXIN® is not only apowerful anti-inflammatory agent, but isalso considered safe and well tolerated,
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patients in tiie control group took^ulfasalazine (a NSAID used totreat inflammatory bowel disease)three times daily for six weeks. Aremarkable 90% of those treatedwith bosweiha showed improve-ment in one or more disease indica-tors, compared to only 60% in thesulfasalazine group who showedsimilar improvement. Even moreimpressive was that 70% of theboswellia-treated patients went intodisease remission, compared to 40%of those taking sulfasalazine. '
Blocking LeukotrienesImproves Asthma Symptoms
Cases of asthma are dramaticallyincreasing. An inflammatory disor-der of the airways, asthma causesshortness of breath, wheezing, chesttightness, and coughing. By blocking5-LOX-induced leukotriene produc-tion, boswellia may offer relief fromthe breathing difficulties that charac-terize asthma.
In a double-blind, placebo-con-trolled study of 80 asthma patients,40 patients took an extract ofboswellia three times daily for sixweeks, and 40 patients took a pla-cebo." Of patients taking boswellia,70% showed an improvement intheir symptoms, including the abil-ity to inhale and exliale normally.Additionally, the boswellia-treatedsubjects demonstrated a decrease ineosinophils. which are white bloodcells associated with allergy andasthma. By contrast, only 27% of theplacebo-treated group demonstratedimproved symptoms.
Conclusion
Every year, scientists are learn-ing more about how inflammationpromotes various disease processes.Recent studies have shed light onthe interplay between pro-inflam-matory lipoxygenase (LOX) enzymesand conditions such as cancer, heartdisease, and asthma.
Long used as a traditional herbalmedicine, boswellia blocks 5-tipoxy-genase (5-LOX), one of the mostdamaging of the LOX enzymes.Laboratory and clinical studies alikedemonstrate that boswellia holdspromise in averting the numerousdiseases associated with excessivelevels of inflammation in the body.Boswellia may benefit adults seek-ing to manage or prevent conditionscaused by the debilitating effects ofchronic inflammation. •
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