TREATMENT OF ALLERGIC DISORDER FROM THE TRADITIONAL ERA …

www.wjpps.com Vol 9, Issue 9, 2020.

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Shende et al. World Journal of Pharmacy and Pharmaceutical Sciences

TREATMENT OF ALLERGIC DISORDER FROM THE

TRADITIONAL ERA TO THE MODERN ERA

Shubham Shende1*, Surendra Dangi

1, Neeraj Upmanyu

1 and Rakesh Raj

2

1School of Pharmacy and Research, People’s University, Bhopal-462037.

2Meerabai Institute of Technology, under DTTE Govt of NCT, New Delhi 110065.

ABSTRACT

The human being appears to be affected with more disease than any

other animal species most common disorders such as allergy, cold,

fever, etc. Allergy is a state of hypersensitivity of the immunosystem

against the allergen, which is entered into the body. Various clinical

disorders associated with allergy-like asthma, hay fever, food allergy,

Urticaria, delayed hypersensitivity. The allergic disorder can be treated

by three ways of control of the environment, drug therapy, and Novel

strategies. Treatment of allergic disorders from the traditional era

people used herbal drug therapy and in the modern era, allopathic

treatment most commonly used. Allopathic drug therapy having various side effects and

researchers work on overcoming the side effect of the allopathic drug. Novel strategies are

used in the treatment of allergy-like peptide vaccines and specific allergen immunotherapy

.after reviewed we concluded that from the traditional era to modern era, treatment of allergy

is better than better for previous treatment and further study continue for the develop a stable

and effective technique for the treatment of allergy.

KEYWORDS: Histamines, Herbal drug, Allopathic drug, Novel strategies, etc.

INTRODUCTION

Phytomedicines has gained increasing popularity due to the lesser side effect and improve

conventional treatment. Allergic rhinitis has two phases Early and late phase. It also is known

as the initial phase, this type of response is seen within minutes after allergen exposure. It is

also known as quick response phase. The late-phase response starts 4 to 8 hrs after allergenic

exposure.

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 9, Issue 9, 1361-1376 Review Article ISSN 2278 – 4357

Article Received on

12 July 2020,

Revised on 02 August 2020,

Accepted on 23 August 2020

DOI: 10.20959/wjpps20209-17175

*Corresponding Author

Shubham Shende

School of Pharmacy and

Research, People's

University, Bhopal-462037.


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Figure No.1: Early phase and late phase.

The herbal drug has a wide range of therapeutic benefits for treating allergic conditions.

Generally, corticosteroids and antihistamine are used in the treatment of allergy. Herbal drug

shows anti-allergic properties which are present in plants; they contain the flavonoids,

Triterpenes, alkaloids, and xanthenes. Herbal medicine shows the therapeutical response by

Specific and non-specific mechanisms. It contains the various bioactive compounds having

specific action. Researcher study on the in-vivo and in-vitro model.to investigates the anti-

allergic properties of herbal medicines. Phytomedicines can act in acute and chronic

conditions.

Pathophysiology

When the allergens enter into the body. The defense mechanism of the body is activated and

captures the allergen by producing IgE-antibodies. Block the release of histamine. Immediate

hypersensitivity response is mainly mediated by mast cells and basophils. In the early phase

of allergic rhinitis occurs after a few minutes of degranulation and production of other

mediators activated by allergens and late-phase response starts at the 4-8 hour after exposure

of allergens.

Mechanisms of Anti-allergic(Anti-histaminic) Drug

When the drug administered it blocks the release of histamines and stabilizes the mast cell

and other mediators responsible for allergy and inflammations. Few drugs block the COX1

and COX2 receptors along with prostaglandin synthesis and Archidinic acid pathways (inhibit

Leukotrienes).


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Clinical disorders associated with the allergy

Figure No.2: Clinical disorders associated with the Allergy.

There are four general principles for clinical management of allergy

(Willsie et al., 2002)

1) Avoid allergens and triggering factors.

2) Evaluation of allergy vaccine therapy.

3) Use of appropriate therapy.

4) Patient education and follow up guidelines.

Global condition of Allergic Disorder

Figure No.3: Classification based on % drug/therapy used in Treatment of Allergic

Disorder.

1) Globally more than 6000 millions peoples suffering from an allergic disorder like rhinitis.

Allergic rhinitis and its impact on asthma guidelines, second-generation antihistaminic is

the first choice to recommend in both children and adults. (Kuna et al.,2016) Due to it


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observed that Anti-histaminic have a 40.4% share in the total market of allergic rhinitis,

then the second-largest used drug is a corticosteroid and fallowed by Decongestant and

other options of treatment. In England, 65% of patients who suffer from allergy. They

used as herbal therapy as Complimentary alternative medicine. In general, literature

observed that 25-50% population and up to 70% of children herbal therapy is preferred.

(Sayin et al.,2013) The global market of allergic rhinitis, based on the number of patients

is found in that region. It divided into America (1st largest), Europe (2

nd larger), Asia-

Pacific, and Middle East & Africa.

2) American dominates the global market of allergic rhinitis, In America increase the cases

of allergic rhinitis cases of allergic disorders, the American Academy of allergy asthma

and immunology estimated that more than 50 million Americans suffer from the allergic

disease annually this represents the 20% of USA population. (Mullol et al.,2008)

3) European region holds the second-larger market, allergic rhinitis patient compare to the

globally approximately 25% patient in Europe suffer from allergic rhinitis. (Kuna et

al.,2016)

4) Asia- Pacific regions, Most of the developing countries like China and India, Maximum

cases due to tobacco, smoke, and other pollutants.

Drug affecting the respiratory system

(Davis et al., 1980)

Name of Drug Therapeutic action

Cromoglycate Anti-allergic activity

Doxantrazole Anti-allergic activity

Pyrimido[4,5-b]quinoline Anti-allergic activity

Phenylenedioxamic acid Anti-allergic activity

Diphenhydramine Hydrochloride Antihistaminic

Meclizine Hydrochloride Antihistaminic

Cetirizine Antihistamine(Nonsedative)

Dextromethorphan HBr Antitussive agent

Codeine Phosphate antitussive agents

Role of vitamins in allergic disorder

A) Vitamin D

Vitamin D is regulating the immunosystem and various diseases are linked with vitamin D

level in blood. Vitamin D and endocrine systems also associate with Allergic disorders like

rhinitis, Asthma, Atopic-dermatic. Vitamin D acts by binding its receptor site which is


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present in various tissues, It is induced the cellular response by triggering cytokines activity.

(Tian et al., 2017).

Mechanism of Action

(By increasing WBC and triggered the function of cytokines)

B) Vitamin C

Vitamin C is also known as ascorbate. Vitamin C has reduced allergic conditions such as

respiratory and cutaneous allergy. It is a powerful antioxidant, vitamin c boost the immune

system and reduced free radicals in the body. (Claudia et al., 2018).

Vitamin C Increases the level of epinephrine (secreted from the adrenal medulla) level in

blood and vitamin c act as a potent antidote of allergic disorders. Vitamin C most commonly

used in skin allergy and some clinical trials already perform by the iv route to check the

inflammatory response of vitamin c.

Mechanism of action

(It responsible for the destruction of histamine structure)


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Treatment of allergic rhinitis is done in three ways: (Bousquet et al., 2008)

1) Control of the environment

2) Drug therapy (Herbal and allopathic)

3) Novel strategies (Peptide vaccine and Allergen-specific immunotherapy).

Control of the environment

An allergic disorder like hay fever and other allergies .which is caused by pollens, dust, and

other pollutants. We can use to remove allergen by HEPA- filter and purification efficacy is

99.95%.

Proper sunlight is required to kill the virus-like rhinovirus which is responsible for cold and

other symptoms of allergy because our body produced vitamin d in the presence of sunlight

and vitamin d is important to regulate the immune system. Few peoples are sensitive to

change in the environment in that case dehumidifier and the air conditioner is used because it

controls the change in temperature.

Plants provide the fresh oxygenated air to the living species and due to deforestation level of

oxygen are reduced and pollutant level is increased. Therefore we need to purify the air. Air

purifier mask is used to remove the pollutant from the air, Air purifier mask contain Two

layers of activated carbon and it is enhanced the purification process. The best air purifier

mask is N99. Which is 99.5% efficacy and purification power.N95 is most commonly used

for purifying the oil pollutants present in the environment.

Herbal Drug Used in allergic disorders

1) Curcuma longa: Curcuma longa is traditional remedies and Curcumin is the active

ingredient of Curcuma longa. Curcuma longa has various pharmacological activities such

as anti-inflammatory activity, anti-allergic activity. In 2018, the Researcher is studied that

Curcumin suppressed compound 48/80. Induced rat peritoneal mast cell degranulation

and release of histamine. Curcumin can inhibit non-specific and mast cell-dependent

allergic reactions. (Yun et al., 2010)The primary obstacle to utilizing Curcumin

therapeutically has been its limited systemic bioavailability but the researcher is involved

in try to increase bioavailability (Louay et al., 2014). Marketed available Curcumin gives

along with black pepper to enhance the bioavailability.

2) Stinging Nettle: Stinging Nettle(Urtica Dioica) is a member of the Urticaceae family.

Nettle is effective for treating seasonal allergy. researcher observed that in the research


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extract of Urtica Dioica inhibits the histamine secretion and the release of other mediators

is responsible for inflammation. It also blocks the COX1 and COX2 receptor by inhibiting

prostaglandin formation and stabilizes the mast cells. (Rocschek et al., 2009) Dose: ½ to 1

teaspoon of Urtica tincture three times a day. (Yarnell et al., 1998).

3) Liquorice: liquorice contains glycyrrhizinic acid and its derivatives responsible for

Antiallergic, antitumorigenic and anti-inflammatory activity, Glycyrrhizin inhibits the

phospholipase A2 enzyme, which is taking part in inflammatory reaction.liquorice

contains steroidal moiety which is the equivalent action of hydrocortisone.(Kaur et al.,

2013).

4) Ginseng: Ginseng is an herbal drug. And genocide is an active phytoconstituents which is

responsible for Antiallergic activity. In 1996, the researcher observed that the extract of

ginseng inhibits the release of beta hexamidase-enzyme from rat basophils cell in the rat.

(Choie et al.,1996)And further Investigation observed that genocide and their metabolites

an antagonistic effect on the release of histamine receptors by using ileum strip of guinea

pig. (Choo et al., 2003).

5) Rosemary: Rosemary contains Rosemarinic acid, Ursolic acid. Rosemarinic acid is used

in the treatment of allergic conditions and respiratory problems. In 2014, The Researcher

observed that 150mg of Rosemarinic acid dose is reduced the Neutrophils and eosinophils

count. (Stansbury et al., 2014).

6) Hardy kiwi: In vivo study conduct by researcher in2009, In the study observed that

reduce the interleukins-5, eotaxin, MCP-1, TARC, and IgE antibodies. (Kim et al., 2009).

7) Apple: In 2005, the researcher observed that apple reduced the cytokines secretion and

reduced the intestinal mast cell protease, T helper cells, and Pro-inflammatory mediators

which is responsible for allergic symptoms. (Tokura et al., 2005).

8) Tomato: Tomato contains Vitamin C and other phytoconstituents which is reduced the

allergic rhinitis symptoms like sneezing, rhinorrhea, and nasal obstructions, It also

overcomes the IgE antibodies and eosinophils counts. (Yoshimura et al., 2007).

9) Amomum compactum: In 2008, In vivo study on mice, aqueous and alcoholic extract of

amomum compactum seed reduced the mucus production, count of eosinophils, and

interlukakines and IgE level. Dose: 100-200mg. (Lee et al., 2008).

10) Khairi: It is also known as the Kalahari Christmas tree. In 2011 Researcher gives an

Ethanolic extract of Dichrostachys cinerea (Khairi) bark to the mice and he observed that

reduced tracheal contraction dependent on epithelium and k-Channels, Dose: 1mg/ml.(Irie

et al.,2011).


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11) Daphnegnidium: It blocks the Cox2 receptor and TNF-α factor due to reducing the

inflammation, Dose:25-100µgml.(Harizi ret al.,2011).

12) Echinodorus grandiflorus: Aqueous leaf extract of echinoderms help to the reduction in

the inflammation by Inhibition the synthesis of the Interluekines, eosinophils and IgE

antibodies Dose:23mg/kg.

13) Withania somnifera: Withania somnifera contain withanolide –A. Researchers observed

that splenocyte, IFN-α, and Interleukins reduced when a dose of Withania introduced in

mice. Dose: 0.1-10ng (Malik et al., 2007).

14) Solanum nigrum: Solanum nigrum contains alkaloids, Cinnamic acid esters, and

steroids. It blocks the LTC4 release and other mediators responsible for Inflammation.

Dose/Concentration: 10.3µl.

15) Bacopa Monieri: Bacopa monieri contains Bacoside, alkaloid, Flavanoids, and

anthraquinone .these are the phytoconstituents that are responsible for therapeutic

activity. It observed that the Ethanolic extract of Bacopa monieri leaves shows mast cell

stabilizing activity. (Samiulla et al., 2001).

16) Neem: Neem (Azadirachta indica) contains Nimbin, nimbinine, nimbandiol, and

quercetin. Ethanolic leaves of Neem show mast cell stabilizing activity (Acharya et al.,

2003) as well as antifungal and antibacterial activity.

Allopathic medicine used in allergic disorders

A) Antihistamines: Antihistamine has prevented the release of histamine from the mast cell.

The first-generation antihistamine is reduced the itching, sneezing, rhinorrhea, and also

causes sedation. Examples: Diphenhydramine, Hydroxyzine, and brompheniramine and

second-generation histamine used to reduce the side effect like sedation examples:

Loratadine, Cetirizine.

Mechanism of action

(Generally H1 receptors)


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B) Decongestants: These are the three type’s oral, topical, and nasal decongestants. Oral

decongestant like Pseudoephedrine is a few side effects like headache, hypertension but it is

contraindicated in cardiovascular disorders. Topical decongestants are used for 4 to 5 days.

Because of topical decongestants having a limitation is rebound the worsening and hyperemia

of symptoms with chronic use. (Kushnir et al., 2011).

Mechanism of action

C) Corticosteroids: Corticosteroids are used for the predominant nasal obstruction.

Beclomethasone, fluticasone propionate is the most commonly used corticosteroids in nasal

obstruction.

D) Mast cell stabilizers: Cromyline sodium (Cromoglycate) is effective in allergic rhinitis

by preventing the release of histamine from mast cells. (Davis et al., 1980).

Mechanism of action

(Indirectly increase the level of Cyclic AMP levels)


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E) Leukotrienes receptor antagonists: Montelukast is used in the treatment of asthma but

also used in the treatment of allergic rhinitis. Leukotrienes receptor antagonist (Leuketrine

modifier) are the inhibit the 5-Lipoxygenase enzyme. The clinical trial demonstrated with

Mentelukast is given in the combination with Loratadine and It observed that better result in a

cause of seasonal allergic rhinitis. (Meltzer et al., 2000).

Mechanism of action

Marketed products

Sr.No. Name of a marketed product Chemical Composition

1 Alerid 10 mg (Tablet) Cetirizine Hydrochloride

2 Avabast 10 (Tablet) Ebastine

3 Avil (Injection) Pheniramine Maleate

4 ELC-M (Tablet) Montelukast sodium and levocetirizine

Hydrochloride

5 Sonocet-AL(Tablet) Levocetirizine,Paracetamol, phenylephrine,

and ambroxol

6 Allegra(Tablet) Fexofenadine

7 Salcet (Syrup) Cetirizine Dihydrochloride and salbutamol

8 Alexo-180 (Tablet) Fexofenadine

9 Punlix (Capsule) Diphenyl hydramine

10 Polyhist (syrup) Pheniramine Maleate

Diagnostic test for Allergy

Diagnostics test used to identify the allergy. Skin allergy identifies by using skin test (scratch

test), skin injection test, and patch test. For the identification of allergen done by the blood

test (by measures the IgE antibodies). Challenge test performed under the supervision of

allergist, Challenge test done for the food and medicine. (Ansotgui et al., 2020).


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Sr.No Diagnostic test for allergy

1 Diagnostic test for Skin allergy Procedure

Scratch test

Clean the test site by alcohol then, Needle

penetrates the skin surface. Draw the mark on

the skin. After 15 minutes observe the skin for

the sign of allergic reaction like red spot(like

mosquito bites) measure the size of spot .after

record the result your skin clean by alcohol to

remove marks

Skin Injection test

( Intradermal test)

Inject the small amount of allergen into the

skin on your arm. Injection site examined after

15 min for signs of an allergic reaction.

Note: Physicians generally inject

penicillin/insect venom as an allergen.

Patch test

Allergen apply to the patch, this patch placed

on the skin (Arm/Back) due to causes contact

dermatitis after 48 hours to wear the patch,

Irritation on the skin at the patch indicated an

allergy

2 Blood test The blood test measures the IgE antibodies to

certain allergen into the blood.

3 Challenge test

This test performs under the supervision of an

allergist. You can eat /breathe a small amount

of allergen. Challenged test perform for check

food and medicine allergy.

Novel strategies for allergic disorder

1) Peptide vaccine (containing T cell epitopes)

The peptide vaccines are novel strategies by the usage of short peptide fragments in the

treatment of allergy .it is a highly targeted immunosystem. The genuine concept of peptide-

induced T-Cell from in vitro studies various clinical trials already done and it observed that T

–cell Reactive short allergen peptide and other peptides are overlapped. When It intra-dermal

administered into the skin immunological mechanism concept already resolved but specific

anergy. Peptide vaccines are used in the food allergy and also used in allergy caused by

pollens. Vaccines are developed for the treatment of chronic disease and most of the

condition protein peptide vaccine is preferred in infections, cancer treatment, and serious

allergic disorders. (Hehir et al., 2016).


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Figure No.4: Peptide vaccine (containing T cell epitopes).

2) Allergen-specific immunotherapy

Allergen-specific immunotherapy is used as a preventive allergy vaccination (for a specific

allergen, food as well as venom allergen).it is based on DNA Technology and peptides.DNA

technology is one of the tools to make allergen-specific immunotherapy. A specific gene is

responsible for a specific activity. We can change the code of gene, which is responsible for

allergy. Specific Recombinant and synthetic allergy vaccination are more safe, effective, and

convenient. (Valenta et al., 2016).

Figure No.5: Specific Immunotherapy.


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Future Study

Allopathic medicine shows quick relief and various side effects and not completely cure the

disease. In that condition, we can use the herbal drug and allopathic drugs in combination.

Herbal drugs contain more than one constituents .they overcome the side effect of the

allopathic drug, such combination we can use in Acute and chronic disorders. Peptide

vaccine has the potential to treat the food allergy in the future, strict avoidance of the

allergen and the new approach for treat food allergy and management of food allergy.

Specific immunotherapy is one of the best approaches for the treatment of allergic disorders

as well as DNA Technology is used to correct the genetic code of gene which is responsible

for allergic conditions. Various vitamins are used in the treatment of allergy, further research

carried out for the development of new treatment strategies.

CONCLUSION

After reviewed, we concluded that from the traditional era to the modern era allergic

treatment is better that better for previous treatment, and further study is required to develop a

new, stable and effective technique for the treatment of allergy.

ACKNOWLEDGMENT

The authors are thankful to the Principal of the School of Pharmacy & Research, People’s

University, Bhopal (Madhya Pradesh), India. for providing to necessary facilities to carry out

this work.

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