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Exploring Herbal Antihistaminics-Natural Allergy Fighters for Comprehensive Health Care

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Puja Ganeshrao Maldhure, Anita Wanjari and Kirti Naharwal
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Correspondence: Dr. Anita Santoshrao Wanjari Professor, Department of Rasashastra and Bhaishajya Kalpana, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, INDIA. Email: anitawanjari7@gmail.com

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June 07, 2024; July 01, 2024; August 27, 2024.

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1.Maldhure PG, Wanjari A, Naharwal K. Exploring Herbal Antihistaminics-Natural Allergy Fighters for Comprehensive Health Care. International Journal of Pharmaceutical Investigation [Internet]. 2024 Dec 5;15(1):10–8. Available from: http://dx.doi.org/10.5530/ijpi.20251739
Published in: International Journal of Pharmaceutical Investigation, 2025; 15(1):10-18. Published online: 05 December 2024DOI: 10.5530/ijpi.20251739

ABSTRACT

Histamine is found in a variety of bodily fluids, platelets, leucocytes, basophils and mast cells in the human body. Mast cells and circulating basophiles store the majority of histamine. Moreover, histamine functions as a neurotransmitter in a variety of cellular physiological processes, including the release of stomach acid, inflammation, allergic reactions and central and peripheral neurotransmission. Histamine is a substance produced by mast cells in the immune system, commonly associated with allergic reactions and their symptoms. Antihistamines are medications designed to counteract the effects of histamine released by the body during allergic responses. Antihistamines block the action of histamine, thereby reducing or alleviating allergy symptoms. The majority of allergic conditions stem from substances such as airborne pollens (from weeds, grass and trees), mites, cockroaches, house dust, animal fur and fungal spores etc., Herbal remedies are increasingly employed to address diverse ailments and enhance various conditions with minimal adverse effects. Antihistaminic effects can be evaluated using extracts from plants or synthetic medications.

Keywords: Histamine, Antihistaminic activity, Mast cells, Basophiles, Allergy

INTRODUCTION

One of the prevalent illnesses that impact people with a variety of symptoms is allergy. Allergies are a prevalent condition that impacts humans with various symptoms and presentations. In recent years, despite overall improvements in population health, there has been an increase in the occurrence of allergies and asthma.1 Allergic disorders cause a great deal of morbidity and have a detrimental effect on the economy.2 Numerous epidemiological investigations have determined the reasons for the rise in upper and lower respiratory tract allergy illness prevalence. Increasing environmental pollution and an increased propensity for people to produce excessive IgE due to a significant shift in the gene pool, altered lifestyles and more knowledge of the illnesses are some of the hypothesized causes.3 Allergies are increasingly prevalent globally, particularly in developed nations. Currently, around 300 million individuals are impacted by allergies worldwide and projections suggest that an additional 100 million will be affected by 2025.4 Over the past few decades, extensive study has demonstrated the significance of mast cells, immunoglobulins, lymphocytes and different types of autacoids in the etiopathogenesis of allergy diseases. Despite the abundance of research on the topic, treating allergic illnesses is still far from acceptable. Treatment options for allergic illnesses are severely limited because of their poor efficacy, side effects and difficulties with patient compliance.5

The Indian medical system known as Ayurveda has recommended a number of medications made from native plant sources to treat allergic diseases including bronchial asthma.6 Since the ancient period, herbal remedies have been employed for their healing properties, effectively treating numerous ailments. The Indian Ayurvedic Medicine system utilizes plants as potent healing components, prompting increased interest in the pharmacological assessment of various plant species employed in traditional medicine systems.7 Ayurvedic texts and other Indian literature document the utilization of various plants to address human health issues. India boasts approximately 45,000 plant species, with numerous believed to possess medicinal properties.8 In the literature plants used for allergy have shown antiasthmatic, antihistaminic and antiallergic activity. Many phytoconstituents have also proved their effectiveness. In this, we discuss the efficacy of antihistaminic plants and their role in health.

METHODOLOGY

The data was collected from different texts, research articles and e-materials available. The search engines were used to collect the data. PubMed, Science Direct, Scopus, Proquest, Google, Google Scholar and Embase databases were used for collecting the data.

Histamine and its receptors

Histamine is synthesized and released by several types of human cells, such as mast cells, basophils, lymphocytes, enterochromaffin cells, platelets and histaminergic neurons.9 Following stimulation, it is stored in vesicles or granules before being released. Histamine exerts its effects on various tissues by interacting with four types of receptors: histamine receptor HR1, HR2, HR3 and HR4, all belonging to the G Protein-Coupled Receptors family (GPCRs).10 The H1 Receptor (HR1), encoded by a gene on human chromosome 3, is responsible for numerous allergic symptoms like itching, runny nose, bronchial constriction and intestinal smooth muscle contraction. Histamine presence stabilizes the receptor in its active state.

Mast cell stabilizing activity

Mast cells, a type of connective tissue, are closely associated with histamine. The release of histamine by mast cells plays a vital role in the body’s inflammatory response.11 Mast cells, also known as mastocytes, play a crucial role in monitoring the immune system of the human body.12 These large cells originate from hematopoietic progenitor cells and are found in various tissues, including the oral cavity, conjunctiva, nose and mucosa of the lungs and digestive tract.13

Mast cells that have been activated by an antigen start subcellular signalling pathways that release a number of mediators, such as histamine, chymase, hydrogen peroxide, tryptase and cytokines.14 This leads to the development of allergic reactions. Thus, mast cell stabilizers play a crucial role in preventing various allergic and inflammatory reactions. By stabilizing mast cells, these medications can help reduce the severity and frequency of allergic reactions, making them valuable in the treatment of conditions such as asthma, allergic rhinitis (hay fever) and allergic conjunctivitis.

Many adverse effects, including as anxiety, weariness, headaches, drowsiness and bleeding, are associated with conventional pharmacotherapy’s low effectiveness.15 Thus, the demand for safe and efficient mast cell stabilizers arises. Plants are a great place to look for new drugs. Strong antioxidants, anti-inflammatory agents and histamine release inhibitors are found in plants high in polyphenols.16

Antihistamine

The treatment of allergic diseases involves the use of antihistamines.17 They are helpful in managing allergies brought on by histamine release. Antihistamine medications, then, alleviate allergy symptoms by maintaining the inactive form of the receptor and preventing the effects of histamine.18 The studies related herbs with antihistaminic activity mentioned in Table 119–33 and Phytoconstituents of herbs having antihistaminic activity mentioned in Table 2.34–82

 

Table 1:
The studies related herbs with antihistaminic activity.

Sl. No.Author and ReferencesJournal and YOPStudy typeTherapeutic regimenSample sizeOutcome
1.G Sridevi et al., 2008The Internet Journal of Pharmacology.In vivoAlcoholic extract of Ocimum sanctum.Guinea pig (400-600 g).Research from multiple trials shows that the extract’s antihistaminic and antianaphylactic properties are primarily caused by its ability to stabilize mast cells, decrease IgE and prevent the production of inflammatory mediators.19
2.P. Venkatesh et al., 2009Journal of Ethnopharmacology.In vivoAlcoholic extract of Curculigo orchioides rhizomes.Male Swiss albino mice (20-25 g).This result shows that mast cell degranulation and immediate-type allergy reactions arising from mast cells are inhibited by COR.20
3.Dinesh Kumar et al. 2011Pharmacognosy Research.In vitro and In vivo.Aqueous extract of stem barks of Ailanthus excelsa Roxb.Isolated adult goat tracheal tissue albino mice (20-25 g), albino rats (150-200 g).The aqueous extract of Ailanthus excelsa Roxb. stem bark exhibits strong antihistaminic action (H1-antagonist) and is thought to have adaptogenic, bronchodilatory and anti-inflammatory properties.21
4.Rahul Hazare et al., 2011African Journal of Pharmacy and Pharmacology.In vitro and In vivoEthanolic extract and essential oil extract of leaves of Piper betel Linn.Isolated guinea pig tracheal chain, Isolated guinea pig ileum, Guinea pigs (350-400 g).Piper betel Linn essential oil and ethanolic extract have antihistaminic properties.22
5.Dnyaneshwar J Taur et al., 2011Journal of Basic and Clinical Pharmacy.In vivoEthanol extract of Clitoria ternatea L. root.Swiss albino mice (25-30 g).The study found that medications with antihistaminic potential reduce catalepsy produced by clonidine, indicating that the ethanol extract of the roots of Clitoria ternatea has antihistaminic properties.23
6.Dnyaneshwar J et al., 2011Oriental Pharmacy and Experimental Medicine.In vivoEthanol extract of Abrus precatorius leaves.Swiss albino mice (25-30 g).EAPL has antihistaminic activity since medications with antihistaminic potential prevent clonidine-induced catalepsy.24
7.Dnyaneshwar J Taur et al., 2011Chinese Journal of Natural Medicines.In vivoEthanol extract Coccinia grandis fruit.Wistar rats (150-170 g) Swiss albino Mice (25-30 g).ECGF helps stabilize mast cell degranulation triggered by antigens and prevents the release of histamine during an anaphylactic reaction.25
8.Yoke Keong Yong et al., 2013BMC Complementary and Alternative Medicine.In vivoAqueous extract of Bixa orellana.Sprague- Dawley rats weighing (200-250 g).Its anti-inflammatory properties could be attributed to the active component of the aqueous extract. It remains to be determined if it functions via stabilizing mast cells.26
9.Pandy Vijayapandi et al., 2013African Journal of Traditional, Complementary and Alternative Medicines.In vitroAqueous, acetone, hexane and methanol extracts of Acorus calamus leaves.Isolated guinea pig ileum.Acorus calamus leaves extracts exerts antihistaminic effect in guinea pig ileum.27
10.Sunita Thakur et al. 2013International Journal of Pharmaceutical Research and Allied Sciences.In vivoEthanolic seed extract of Moringa oleifera.Wistar albino rats (150-170 g)Moringa oleifera ethanolic extract has the ability to stabilize mast cells and has anti-allergic properties, making it useful in the treatment of asthma.28
11.Sangilimuthu Alagar Yadav et al., 2015Journal of Complementary and Integrative Medicine.In vivo and in vitro.Methanol extract of Tragia involucrata L.Isolated guinea pig ileum, Guinea pigs (250-350 g)On histamine-induced guinea pigs, isolated 5-hydroxy- 1-methylpiperidin-2-one from Tragia involucrata L. has strong antihistamine properties.29
12.Hassan M Qureshi et al., 2015Pakistan Veterinary Journal.In vitroEthanolic and aqueous extract of Murraya koenigii leaves.Isolated tissues of guinea pig ileum, rabbit trachea and jejunum.Murraya koenigii leaf extracts, both aqueous and ethanolic, have potential applications in the treatment of gastrointestinal and respiratory conditions.30
13.Firdous A. et al., 2017Annals of plant sciences.In vivoEthnolic extract of cuscuta reflexa Roxb.Male albino rats (150-200 g).The study shows that the ethnolic extract of Cuscuta reflexa stabilizes mast cells in experimental animals.31
14.Ms. Asha Jadhav et al., 2018Int. Journal of Pharmaceutical Sciences and Medicine (IJPSM).In vitroMethanol extract of Raphanus sativus L.Goat tracheal tissue.Raphanus sativus L. leaf methanolic extract inhibit variety of contractile stimuli, including histamine.32
15.Vandana Athiya et al, 2019Journal of Drug Delivery and Therapeulics.In vivoMethanol extract of Adhatoda vasica.Swiss albino mice (25-30 g).The methanol extract of Adhatoda vasica leaves has antihistaminic activity since medications with antihistaminic potential reduce clonidine-induced catalepsy.33

 

 

Table 2:
Phytoconstituents of herbs having antihistaminic activity.

Sl. No.Name of herbsPhytoconstituents
1.Ailanthus excelsa Roxb.Quassinoids – Stem bark contains quassinoids like 1,4-dihydroexcelsin, excelsin,34,35 3 , 4, dihydroexcelsin, 2, 4-dihydroexcelsin,36 glaucarubol,13,18-dehydroexcelsin,37 ailanthinone, ailanex A, ailanex B, polyandrol and glaucarubolon,38–39 glaucarubol,40 Triacontane and hexatriacontane.41
2.Piper betel Linn.Phytochemical constituents of the essential oil of the betel leaf are terpenes and phenols,42 Hydroxychavicol (HC)/Hydroxychavicol Acetate (HCA), Chavibetol,43 Piperbetol, allylpyrocatechol, carvacol, PiperitolCaryophyllene, Piperbetol, Eugenol, Isoeugenol, Safrole, Chavicol, Anethole,44 β-sitosterol, Chavibetol,cadinene,45 Hydroxychavicol.46
3.Clitorea ternatea L.1,1-diphenyl-2-picrylhydrazyl,47 β carotene, taraxerol and teraxerone, Stigmast-4-ene-3,6, diene,starch,resins and tannins.48
4.Cuscuta reflexa Roxb.Cuscutarosides A and B, steroidal glucoside, 2H-pyran-2-one glucosides, 7β-methoxy-βsitosterol 3-O-β-glucopyranoside.49
5.Curculigo orchioidesn-hexadec-9,11-dienyl cinnamate, n-heneitriacont-13-en-5,10-diol hex-2’-en-1’- oate, n-decan-3-olyl pent-3’en-1’-oate, n-tridecanyl-hex-2’,4’- dien-1’-oate.50
6.Tragia Involucrata L.T. involucrata leaf; contains, vinyl hexylether and 2-methylnonane,51 Antihistamine 5-hydroxy- 1-methylpiperidin-2-one.
7.Bixa orellana L.Pentanoic acid, Phenol, 2-Butamine, Acetic acid, Benzoic acid. Pantolactone,52 Bixein, Isobixin, Croceti, Bixaghanene, Ellagic acid, Tryptophan, Tomenstosic acid, Salicylic acid, Falvonoid, Phenylalanine, Threonine, Bisulfates, Sterols, Saponins, Tannis,53 Terpenoids, Carotenoids.54
8.Acorus calamus Linn.Glycosides, flavonoids, saponins, tannins, polyphenolic compounds, mucilage, volatile oil,55 Cisisoelemicine, cis and trans isoeugenol and their methyl ethers, P-cymene, α-selinene, camphene, bgurjunene, β-cadinene, camphor, terpinen-4-ol, βasarone, αasarone, elemicine.56
9.Abrus precatorius Linn.Abrin, trigonelline,57 hemiphloin, abruslactone A,58 abrusoside A,59 abrusoside B, abrusoside C, abrusoside D,60 Xylosegalactose, arabinose,61 hypaphorine, precatorine,62 glycyrrhizin,63 montanyl alcohol, pinitol, inositol D monomethyl ether.64
10.Coccinia grandis Linn.2-methoxy-4-vinylphenol, 12-octadecadienoic acid, benzofuranone, 13-octadecadienol 9, phenol-2-methoxy-5(1-propenyl), Phenol, 3,7,11,15-tetramethyl-2- hexadecen-1-ol, 2.4-bis(1,1-dimethylethyl), undecanol, 2(3h)-furanone, 2-methyl-z,z-3, hexadecanoic acid methyl ester, β-sitosterol acetate, campoesterol, stigmatosterol, tocopherol, campesterol and ethisteron.65
11.Murraya koenigii Linn.Mahanine, Mahanimbine, Murrayanol,66–68 O-Methylmurrayamine A, Koenigicine, Murrayone (Coumarine), Mahanimbicine, Bicyclomahanimbicine, Phebalosin,69–70 Euchrestine B, Girinimbilol, Isolongifolene
12.Oscimum sanctumß-caryophyllene, methyl eugenol,71,72 (E)-caryophyllene, Eugenol and β-elemene,73 methyl chavicol and linalool,74 β-bisabolene, 1,8-cineole,75 Isocaryophyllene.
13.Raphanus Sativus LConcentration of calcium, potassium, sodium, fiber, macronutrients, fatty acids and nonflavonoid polyphenols is high in leaves.Flavonoids- anthocyanins, flavanol catechinTerpenes and derivatives- β-carotene and phytol.76
14.Adathoda vasica Nees.Quinazoline alkaloid, vasicine (1, 2, 3, 9-tetrahydropyrrole [2, 1-b] quinozolin-3-ol,77 C11H12N2O), adhatonine, adhavasinone, adhatodine, vasicinol, vasicinone, vasicinolone, N-oxide vasicine, vasicol, Betaine, steroid β-sitosterol and alkanes.78
15.Moringa oleiferaSeeds contain high concentrations of benzylglucosinolate, 4-(α-1-rhamnopyranosyloxy)- benzylglucosinolate, 4-(α-l-rhamnosyloxy) benzylisothiocyanate, O-ethyl-4-(α-l-rhamnosyloxy) benzyl carbamate.79–82

 

DISCUSSION

Ayurveda, an Indian medical system, has prescribed a number of medications made from locally available plant sources to treat allergy diseases and bronchial asthma.83 Plants have served as medicinal remedies since ancient times, providing treatments for various common ailments throughout human history. Since the dawn of civilization, humans have sought outremedies for different illnesses through their own methods.84 The assessment of the pharmacological properties of different plants utilized in traditional medicine is gaining more and more attention.

Many human cells, including basophils, mast cells, lymphocytes, histaminergic neurons, platelets and enterochromaffin cells, are responsible for the synthesis and release of histamine.

The inflammatory reaction is set off by histamine. Histamine is produced by basophils and mast cells in the surrounding connective tissues in response to invasive infections. White blood cells and some proteins can more easily enter infected tissues through capillaries that are more permeable due to histamine.

Antihistamines are a type of medicine that is often used to treat a number of allergic disorders. The body’s overproduction of histamine causes allergic and inflammatory reactions. Natural remedies have historically been used to counteract the effects of histamine.

Several plants and their derived natural products have been reported as safe, effective and inexpensive antiallergic agents. viz, as per G Sridevi et al., Ocimum sanctum demonstrates efficacy in treating asthma by stabilizing mast cells, suppressing IgE and inhibiting inflammatory mediator release, based on experimental findings. According to P. Venkatesh et al., Curculigo orchioides rhizomes contain alkaloids, polyphenols, saponins, steroids and tannins, which collectively contribute to its medicinal properties, including allergy alleviation. Dinesh Kumar et al. 2011 found that, the bark extract of Ailanthus excelsa Roxb. significantly reduced paw volume, potentially by inhibiting antigen-antibody reactions or acting as an antihistamine. It also decreased clonidine-induced catalepsy by possibly antagonizing H1 receptors, indicating significant antihistaminic activity. Similarly, as per Rahul Hazare et al., both the ethanolic extract and essential oil of Piper betel Linn. demonstrated antihistaminic properties, inhibiting histamine-induced contractions in guinea pig tracheal and ileum preparations, likely through H1 receptor antagonism. Dnyaneshwar J Taur et al., demonstrated Clitoria ternatea L. root extract, known for its anti-inflammatory effects, effectively reduced clonidine-induced catalepsy, suggesting antihistaminic activity mediated via H1 receptor antagonism.

On other hand, according to Dnyaneshwar J et al., Ethanol extract of Abrus precatorius Leaves (EAPL) possesses significant antihistaminic activity, as demonstrated by its inhibition of clonidine-induced catalepsy, mediated by histamine through H1 receptors, thereby suggesting its potential as an antihistaminic or mast cell stabilizing agent.

As per Dnyaneshwar J Taur et al., the ethanol extract of Coccinia grandis fruit contains saponin, steroids, alkaloids, flavonoids and glycosides. Saponins stabilize mast cells, exhibiting antiallergic and antihistaminic properties. Glycosides have antiasthmatic effects by relaxing tracheal smooth muscle and reducing allergies. Flavonoids like apigenin and luteolin possess bronchodilator activity, inhibiting histamine release for antiallergic effects.

ECGF stabilizes mast cells, inhibits histamine release and prevents catalepsy, showing promise for asthma treatment due to its antiallergic and mast cell stabilizing effects. Yoke Keong Yong et al., found that Bixa Orellana’s aqueous extract possesses anti-inflammatory properties by reducing vascular permeability through the suppression of biochemical mediators such as VEGF and NO in tissues, indicating its potential as an anti-inflammatory agent. As per Pandy Vijayapandi et al., Acorus calamus contains a diverse range of phytochemicals, including terpenoids, steroids, xanthones, lignans, flavones, glycosides, flavonoids, saponins, tannins, polyphenolic compounds, mucilage, glucoside, alkaloids and essential oils like calamen, clamenol, calameon, asarone and sesquiterpenes. Both methanol and aqueous extracts of its leaves exhibit antimuscarinic activity, suggesting possible bronchodilator effects and validating its traditional use in asthma treatment. According to, Sunita Thakur et al., Moringa oleifera extract contains steroids, saponins, alkaloids, flavonoids and glycosides. Glycoside, saponins stabilize mast cells, while flavonoids like apigenin and luteolin inhibit histamine release from basophils and neutrophils. They also suppress histamine release triggered by 48/80, showing promise for asthma treatment due to anti-allergic and mast cell stabilizing effects. Sangilimuthu Alagar Yadav et al., identified 5-hydroxy-1-methylpiperidin-2-one isolated from Tragia involucrata L. leaves acts as a potent muscle relaxant, bronchodilator and anti-allergic agent, particularly effective against histamine-induced muscle contraction in guinea pigs. It exhibits strong antihistamine properties as evidenced by its high docking score, energy and interactions.

According to Hassan M Qureshi et al., both ethanolic and aqueous extracts of Murraya koenigii Linn. demonstrated antihistaminic and anticholinergic activities. They caused a rightward shift in histamine concentration response curves and dose-dependent relaxation of pre-contracted isolated rabbit trachea and jejunum tissue, indicating potential for treating airway and gastrointestinal disorders. Firdous A. et al., found that, the ethanolic extract of Cuscuta reflexa demonstrated mast cell stabilizing activity, likely due to its flavonoids and saponins. As per Ms. Asha Jadhav et al., The methanolic extract from Raphanus sativus L. leaves contains saponins, flavonoids, tannins, glycosides and carbohydrates. It significantly inhibits dose-dependent contraction induced by histamine, suggesting competitive antagonism for H1 receptors on smooth muscle. This indicates its ability to effectively inhibit responses to various contractile stimuli, including histamine, thus possessing antihistaminic action. According to Vandana Athiya et al., Adathoda vasica extract contains carbohydrates, glycosides, alkaloids, saponins, flavonoids, tannins and phenolic compounds. Its methanol extract shows significant antihistaminic activity, likely due to its H1-antagonist properties, contributing to bronchodilating, anti-inflammatory and adaptogenic effects.

Cite this article:

Maldhure PG, Wanjari A, Naharwal K. Exploring Herbal Antihistaminics-Natural Allergy Fighters for Comprehensive Health Care. Int. J. Pharm. Investigation. 2025;15(1):10-8.

ACKNOWLEDGEMENT

The authors acknowledge the support given by DMIHER university, VC, DMIHER(DU).

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest.

ABBREVIATIONS

HRHistamine receptor
GPCRG protein-coupled receptors
EAPLEthanol extract of Abrus precatorius leaves
ECGFEthanol extract Coccinia grandis Fruit
HCAHydroxychavicol acetate
IgEImmunoglobulin E

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1.Maldhure PG, Wanjari A, Naharwal K. Exploring Herbal Antihistaminics-Natural Allergy Fighters for Comprehensive Health Care. International Journal of Pharmaceutical Investigation [Internet]. 2024 Dec 5;15(1):10–8. Available from: http://dx.doi.org/10.5530/ijpi.20251739