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Pharma Science Monitor 5(2), Apr-Jun 2014
PHARMA SCIENCE MONITOR
AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES
Journal home page: http://www.pharmasm.com
MANAGEMENT OF ASTHMA BY HERBAL THERAPY WITH SPECIAL
REFERENCE TO POLYHERBAL FORMULATION
C. S. Barik1*, S. K. Kanungo1, J. R. Panda2, N. K. Tripathy3
1
Institute of Pharmacy and Technology, Salepur, Odisha, India.
Roland Institute of Pharmaceutical Sciences, Khodasingi, Berhampur, Odisha, India.
3
Department of Zoology, Berhampur University, Bhanja Bihar, Odisha, India.
2
ABSTRACT
In traditional systems of medicine, various plants have been acknowledged to be useful for the
treatment of different types of respiratory disorders including asthma. In few decades the use of
medicinal plants has been increased dramatically throughout the world. Current synthetic drugs
used in pharmacotherapy of asthma are unable to act at all the stages and targets of asthma.
However some herbal alternatives are occupied a significant place in asthma are confirmed to
provide symptomatic relief and support in the management of the disease. In case of asthma the
herbal drugs have exhibited remarkable results in various target specific biological activities such
as bronchodilation, mast cell stabilization, anti-inflammatory, anti-spasmodic, anti-allergic, antianaphylactic, immunomodulatory and inhibition of mediators such as leukotrienes, lipoxygenase,
cyclooxygenase, platelet activating, phosphodiesterase, histamine, bradykinin, endothelin and
cytokines, in the treatment of asthma. This current review is an attempt to accumulate
pharmacological and clinical findings of the herbal drugs along with their mechanism used for
the management of asthma. It also signifies the requirement for the development of polyherbal
formulations containing a variety of herbs useful for the prophylaxis as well as treatment of
asthma.
KEYWORDS: Asthma, Herbal therapy, Polyherbal, Traditional systems.
INTRODUCTION
Among several respiratory disorders affecting man, bronchial asthma is the most common one.
Asthma is a chronic disease characterized by various airway obstruction, airway inflammation
and bronchial hyper responsiveness[1]. These symptoms may be due to liberation of endogenous
and intrinsic mediators like histamine, leukotrienes, bradykinin, prostaglandins, nitric oxide,
platelet activating factors, chemokines and endothelin from mast cells during the allergic
reactions and inflammation of the air passages in the lungs. It is also known that asthma can be
triggered by various infections, dust, cold or warm air, exercise, emotion, perfumes, chemicals,
various foods, tobacco smoke, genetics and histamine[2]. Nearly 8-10% of the world population
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suffering from bronchial asthma. Its increased prevalence, morbidity and mortality rates have
documented the rising seriousness of asthma in the common population in the past 20 years.
Large number of anti-asthmatic drugs belonging to different classes such as α2 agonists
(Ephedrine), corticosteroids (Hydrocortisone, Prednisolone), mast cell stabilizers (Sodium
chromoglycate,
Kitotifen),
methylxanthines (Theophylline,
Aminophylline),
leucotriene
antagonists (Montelukast, Zafirlukast) are widely used in the treatment of asthma. But they are
not completely safe for long term use and hold some side effects like immune suppression,
cardiac abnormalities, central nervous system depression, hyperglycemia etc. Muscle tremor and
hypokalemia are the major adverse effects of β2 agonists. Systemic corticosteroids have common
side effects such as disturbance of adrenal function and immune suppression[3]. Therefore, there
is a dreadful demand to identify a effective and safe remedy for the treatment of bronchial
asthma. The traditional systems of medicine and the accessibility of a large array of medicinal
plants in the universe have significantly facilitated the researchers to develop wholehearted
interest in their screening, research and development[4]. Thus an attempt has been made to
highlight the antiasthmatic medicinal plants in this review. The polyherbal formulations
described in Ayurveda have been the basis of treatment of various human diseases including
asthma. This present review gives more prominence on polyherbal formulations used for the
management of asthma.
Evaluation of therapeutic effect of a polyherbal formulation in patients of asthma with different
kind of temperament was carried out. In a clinical trial carried out in Ajmal Khan Tibbiya
College hospital during 2000 to 2003, the therapeutic response of a polyherbal formulation of
Barg-e-aroosa, Gul-e-Zoofah and Aslussoos, was found encouraging in patients having Balghami
Mizaj(Phlegmatic temperament) while least response was observed in patients with saudavi
Mizaj (Melancholic temperament). The study showed that the concept of ancient Unani scholars
about asthma is true and scientific. Thus this polyherbal Formulation exhibited significant effect
on patients with asthma and may be a better alternative to present conventional drugs used for
the treatment of all kinds of asthma[5].
The antiasthmatic potential of a polyherbal formulation was evaluated using several
experimental models. Adult Wistar albino rats were used for mast cell stabilization protocol.
Acetylcholine and histamine-induced bronchospasm were conducted on guinea pigs. The results
of the acetylcholine and histamine-induced bronchospasm showed bronchospasmolytic activity
of polyherbal formulation at the dose of 300 mg/kg, p.o. The spasmolytic effect was
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characterized by prolongation of onset of bronchospasm and reduction of asphyxia as compared
to control group. In the mast cell stabilization paradigm, compound 48/80 treatment produced
76% of mast cell degranulation. Polyherbal formulation at the concentration of 1, 10, and 100
μg/ml showed dose-dependent significant reduction in mast cell degranulation as compared to
the compound 48/80-treated animals. The probable mechanism for the antiasthmatic action of the
polyherbal formulation could be antihistaminic, anticholinergic and mast cell membrane
stabilization[6].
Antiasthmatic activity of Zeal herbal granule was carried out against 48/80 induced mast cell
degranulation. The percentage mast cell degranulation was calculated at different concentration
levels such as 1, 10, 100 and 1000 µg/ml. Zeal herbal granule exhibited significant protection of
rat mesenteric mast cells from disruption caused by compound 48/80. The tested herbal granule
also displayed significant dose dependent effect in percentage mast cell degranulation at different
dose levels in comparison to negative control. The study showed that the Zeal herbal granule has
significant antiasthmatic activity[7].
The potency of an herbal drug formulation was evaluated for its efficacy in bronchial asthma by
Singhal et al. Lung function test was performed before and after the treatment to evaluate the
patients. Two parameters, peak expiratory flow rate and forced expiratory volume in one second
after the treatment showed noticeable improvement with side effects of the test drugs[8].
A study was carried out to evaluate the usefulness of Bresol in the management of bronchial
asthma and its adverse effects if any and to determine patient compliance by Manoj et al[9].
Patients were administered Bresol tablets at a dosage of two tablets twice daily for a period of 30
days in adults and one tablet twice daily for the same period in children in the age group of 12-18
years. They were evaluated on Days 0, 15 and 30 for subjective improvements in dyspnea,
cough, wheezing, rhonchus, and tightness of the chest, difficulty in expectoration, rhinitis,
sneezing, fever and paroxysmal nocturnal dyspnea. Results of the study showed a significant
improvement in all the clinical parameters of asthma such as dyspnea, cough, wheezing,
rhonchus, tightness of the chest, difficulty in expectoration, rhinitis, sneezing, fever and
paroxysmal nocturnal dyspnea. None of the patients presented with any adverse effects. All the
patients completed the treatment and compliance to the study drug was good without any
dropouts. This indicates safety and efficacy of Bresol tablets in patients of bronchial asthma.
Each Bresol tablet contain the extract of Curcuma longa, Ocimum sanctum, Adhatoda vasica,
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Trikatu, Triphala, Embelia ribes, Cyperus rotundus, Cinnamomum zeylanicum, Elettaria
cardamomum, Cinnamomum tamala and Mesua ferrea.
A study was aimed to formulate, standardise and evaluate the pharmacological activity of
polyherbal capsule recommended as Antiasthamatic agent by Madheswari et al[10]. Selective
combination of herbals in extract form which individually proven for their efficacy in asthmatic
activity such as Adhatoda vasica, Tylophora asthmatica, Piper longum, Solanum trilobatum and
Alpinia galanga were formulated as capsule. Raw materials, formulation development and
finished capsule were standardized with improved formulation parameters. Granulation was done
by wet granulation technique. The polyherbal capsule formulation was subjected to in-vivo
evaluation for its antiasthmatic activity using histamine induced bronchospasm in guinea pigs.
During acute toxicity study the polyherbal capsule was found to be safe up to 2000 mg/kg body
weight. The polyherbal formulation was administered with a dose of 400 mg/kg showed that it
was more significant than 200 mg/kg when compared with standard drug promethazine 300
mcg/kg. The Polyherbal formulation at a dose of 400 mg/kg showed maximum antiasthmatic
activity.
Ethanolic extract of the aerial parts of Aerva lanta was prepared and studied at 100 μg/ml in the
isolated goat tracheal chain preparation model to find out their antiasthmatic activity. The extract
was studied at 30 and 60 mg/kg doses orally in clonidine induced catalepsy and mast cell
degranulation in mice. The extract illustrated antiasthmatic activity[11].
Hydro alcoholic extract of leaves of Ageratum conyzoides was prepared by Tote et al[12]. The
extract was subjected for its antihistaminic activity at the doses of 250, 500 and 1000 mg/kg by
clonidine induced catalepsy in mice. The extracts displayed antihistaminic activity by inhibiting
clonidine induced catalepsy in mice.
Amburana cearensis is a medicinal plant common to the Brazilian Northeastern “caatinga”
(savannah) and popularly used in the treatment of respiratory tract diseases including asthma.
The flavonoids isokaempferide isolated from trunk barks of A. cearensis showed significant
relaxation of potassium chloride induced contraction on guinea pig trachea[13].
Asystasia gangetica is an important traditional plant used in the management of asthma. Hexane,
ethylacetate and methanol extracts of the leaves of A. gangetica were prepared by Akah et al[14].
The extracts were subjected for antiasthmatic activity using guinea pig trachea, rat stomach strip,
guinea pig ileal preparation and egg albumin-induced acute inflammation. The results indicated
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that the extracts did not exhibit contractile or relaxant activity in isolated tissue preparations;
however, they inhibited the contraction evoked by spasmogens.
Bacopa monnieri a widely used medicinal plant was selected to test its antiasthmatic activity by
Samiulla et al[15]. Various solvent extracts of the leaves such as petroleum ether, chloroform,
methanol and water were prepared and are tested at the dose of 10 μg/mL for mast cell
stabilizing activity in rats. The result of the investigation observed that all the extracts
significantly inhibit mast cell degranulation.
The gum resin of B. serrata is well known in the Indian Ayurvedic system of medicine as Salai
guggal and contains boswellic acid as an important active principle which has been shown to
inhibit leukotriene biosynthesis. In a six week, double blind, randomized clinical trial was
conducted by Gupta et al[16] in 1998 taking 80 adult patients with bronchial asthma. The effect of
B. serrata gum resin was compared with placebo (lactose). The alcoholic extract of B. serrata
roots containing boswellin, boswellic acids which inhibit LT biosynthesis and block synthesis of
5‐HETE and LTB4.
Cassia sophera is used traditionally for treatment of asthma and bronchitis. Chloroform, ethyl
acetate and ethanol fractions isolated from ethanol extract of the leaves of C. sophera by Nagore
et al[17]. The isolated compounds possesses significant antiasthmatic activity in carrageenan
induced paw edema, histamine induced bronchoconstriction, clonidine and haloperidol induced
catalepsy, milk induced leukocytosis and eosinophilia and passive paw anaphylaxis animal
models at doses 250, 500 and 750 mg/kg and this activity may be due to the presence of
flavonoids.
Casuarina equisetifolia is an evergreen tree possesses variety of pharmacological activities. The
methanol extract of wood and bark were prepared and tested for their antihistaminic activity by
inhibiting the histamine induced contraction of trachea (10-80 μg/ml), clonidine induced
catalepsy and mast cell degranulation at the doses 100 mg/kg by Aher et al[18]. The extract
exhibited significant antihistaminic activity by these models.
Clerodendrum serratum known as bharangi in Ayurveda, ethanol extract of roots of C. serratum
showed antiasthmatic activity using isolated goat tracheal chain preparation, clonidine induced
catalepsy, milk induced leucocytosis and eosinophilia in mice at different doses such as 50, 100
and 200 mg/kg[19].
Crinum glaucum is popular in Yoruba of South West Nigeria. Traditional medicine practitioners
reported it as an effective remedy in the relief of cough, asthma and convulsions. The aqueous
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extract of C. glaucum acquire antiallergic activity at 100-400 mg/kg body weight by reduction in
area of dye leakage in passive cutaneous anaphylactic reaction, protecting degranulation of mast
cell and histamine induced bronchoconstriction in the guinea pig[20].
Curculigo orchioides is a small herbal plant widely distributed in different countries of the world
such as India, China, Malaya and Japan. Alcoholic extract of C. orchioides rhizomes at doses
100-400 mg/kg showed mast cell stabilizing and antihistaminic activity on compound 48/80induced mast cell degranulation and systemic anaphylaxis. It also inhibited histamine induced
contraction in goat trachea, guinea pig ileum and bronchoconstriction in guinea pigs; egg
albumin induced passive paw anaphylaxis in rats; milk induced leucocytosis and eosinophilia;
clonidine induced catalepsy in mice[21].
Eclipta alba is famous for its traditional uses. The ethanol extract was prepared and tested for its
antianaphylatic and antihistaminic activities. The ethanol extract showed significant
antianaphylactic and antihistaminic activity at 250 and 500 mg/kg on compound 48/80-induced
degranulation of mast cell, egg albumin induced passive cutaneous and paw anaphylaxis;
bronchoalveolar lavage study on guinea pig trachea and determination of histamine[22].
Euphorbia hirta popularly known as asthma weed, which is an herbaceous wild plant which
grows in the hotter parts of India. Ethanol extract of whole aerial part of the plant was prepared
and tested from lower to higher concentrations i.e., 100-1000 mg/kg showed antihistaminic and
antiallergic activity by inhibiting the passive cutaneous anaphylaxis and paw anaphylaxis
reaction; protection of mast cell from degranulation[23].
The antiasthmatic activity of Ayurvedic polyherbal formulation each 20 ml contains, extracts of
Swertia chirata, Azadirachata indica, Terminalia chebula, Terminalia belerica, Emblica
officinalis, Trichosanthes cucumerina, Adhatoda vasica, Tinospora cordifolia, Fumaria
parviflora, Eclipta alba each 731 mg. Antiasthmatic mechanism of using propranolol, which
antagonized relaxant effect of polyherbal formulation on histamine induced contraction, showed
the activity through goat tracheal β receptor activation. This gives antiasthmatic potential of this
polyherbal formulation[24].
Momordica dioica is a climbing creeper plant. Its fruits and leaves are traditionally used as
medicinal agent of asthma, leprosy, bronchitis and fever. Methanol and aqueous extract of pulp
possesses antihistaminic activity by inhibiting clonidine induced catalepsy in mice at the dose of
50 mg/kg[25].
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Aqueous extract of ripe olives possesses antiasthmatic activity by inhibiting clonidine induced
peritoneal mast cell degranulation in rats and catalepsy in mice at doses 4 and 8 mg/kg and also
by protecting histamine induced contraction of goat trachea and guinea pig ileum at
concentration of 100 μg/mL[26].
Piper betel is traditionally used to cure cough, cold, pruritis, asthma and rheumatism. Ethanol
and aqueous extract of the leaves at doses 100 and 200 mg/kg possesses antiasthmactic activity
on histamine induced bronchoconstriction in guinea pig and histamine induced dose dependent
contraction of guinea pig tracheal chain and isolated guinea pig ileum preparation[27].
Ethanol and aqueous extracts of whole plant Striga orobanchioides showed antihistaminic and
mast cell stabilizing activity by inhibiting histamine induced contractions of the guinea pig ileum
at the concentration 2.5-25 μg/ml in a dose associated manner and inhibiting degranulation of
mast cells at 100 and 200 mg/kg[28].
Sphaeranthus indicus is a medicinally important plant used as folk medicine. The ethanol extract
at the doses of 150, 300 mg/kg and its ethyl acetate extract at the dose of 100, 150 and 300
mg/kg demonstrated slightly better protection against sheep serum and compound 48/80induced mast cell degranulation than the standard drug ketotifen. This exhibited it antiasthmatic
potency[29].
In vitro anti-asthmatic activity of the fruit extracts of Sapindus mukorossi and Piper nigrum was
studied by using acetylcholine induced contraction of goat tracheal chain preparation model of
bronchial asthma. Significant decrease in acetylcholine induced contraction of goat trachea was
observed in the presence of aqueous extract of fruits of these above two plants. Thus the study
revealed that the aqueous extract of fruits of these two plants has good antiasthmatic activity[30].
The effect of ethanol extract of bark of Cordia subcordata at 25, 50, 100 mg/kg doses orally in
the isolated goat tracheal chain preparation, passive paw anaphylaxis in rat was studied by Selvi
et al[31]. The extract showed significant dose-dependent antiasthmatic activity in all these models.
It was observed that ethanol extract inhibits contraction produced by histamine in the isolated
goat tracheal chain preparation. The study revealed that Cordia subcordata extract exhibits
significant percentage decreased contraction at concentration 80 μg/ml in goat tracheal chain
preparation. Similarly there was significant inhibition in rat paw edema at the dose 50 mg/kg of
ethanol extract of bark of Cordia subcordata, in all time intervals when percentage inhibition
was calculated but more specific effect was seen at 3hour interval time. Paw edema volume also
significantly decreased in all time intervals at this dose only.
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Anti-asthma herbal medicine intervention (ASHMITM), a combination of three traditional
Chinese medicinal herbs developed by Bolleddula et al[32], has confirmed its effectiveness in
both mouse models of allergic asthma and a double-blind placebo-controlled clinical trial in
patients with asthma. The study was designed to determine if the anti-inflammatory effects of
individual herbal constituents of ASHMITM exhibited synergy. Effects of ASHMI and its
components aqueous extracts of Lingzhi (Ganoderma lucidum), Kushen (Sophora flavescens)
and Gancao (Glycyrrhiza uralensis), on Th2 cytokine secretion by murine memory Th2 cells
(D10.G4.1) and eotaxin-1 secretion by human lung fibroblast (HLF-1) cells were determined by
measuring levels in culture supernatants by enzyme linked immunosorbent assay. Potential
synergistic effects were determined by computing interaction indices from concentration-effect
curve parameters. Individual Lingzhi, Kushen and Gancao extracts and ASHMI (the combination
of individual extracts) inhibited production of interleukin IL-4 and IL-5 by murine memory Th2
cells and eotaxin-1 production by HLF-1 cells. By comparing the interaction index values they
found that constituents in ASHMITM synergistically inhibited eotaxin-1 production as well as
Th2 cytokine production.
Pistacia integerrima belongs to family Anacardiaceae is popularly known as Karkatakashringi in
Ayurveda and in the Indian traditional medicine it is used as a folk medicine in the treatment of
allergies, asthma, coughs etc. A study was conducted to find out the activity of aqueous extract
of the galls against the mast cell stabilization in rats, histamine-induced bronchospasm in guinea
pigs and spasmolytic activity in isolated guinea pig tracheal chain preparation. The extract was
subjected to phytochemical screening and found to contain essential oils, volatile oils, tannins,
phenolics, flavonoids, carbohydrates and resinous matters. The rats were pretreated with the
extract (27 and 54 mg/kg p.o.) and the antiasthmatic effect was compared with that of
Prednisolone (10 mg/kg p.o.) on disruption rate of actively sensitized mesenteric mast cells of
albino rats when challenged with antigen (horse serum along with triple antigen vaccine) and the
extract (23.25 and 46.50 mg/kg p.o.) and the antiasthmatic effect was compared with that of
Ketotifen (1 mg/kg p.o.) on histamine aerosol-induced bronchospasm in guinea pigs. The results
underlined that the aqueous extract of P. integerrima galls treatment for ten days resulted in
significant effect on disruption rate of actively sensitized mesenteric mast cells of albino rats
when challenged with antigen and significant protection against histamine aerosol-induced
bronchospasm in guinea pigs and showed the spasmolytic activity against histamine induced
contractions in isolated guinea pig tracheal chain preparation. Antiasthmatic activity of aqueous
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extract of Pistacia integerrima galls may be possibly due to the membrane stabilizing potential,
suppression of antibody production and inhibition of antigen induced histamine release[33].
A study was carried out by Iyekowa et al[34] to evaluate the antiasthmatic activity of methanolic
extract obtained from Portulaca oleracea. Bronchial asthma was induced in guinea pigs using
10% histamine dihydrochloride. Chloropheniramine (8 mg/kg), saline (5 ml/kg) and the
methanolic extract of P. oleracea (40, 60 and 80 mg/kg) were administered orally for 30 min
prior to their exposure to histamine aerosol. Disponea was not seen in all the guinea pigs treated
with chloropheniramine, but was observed in all the guinea pigs treated with saline and a
concentration of the extract (80 mg/kg) at the 3rd and 5th minutes. Guinea pigs which were
administered with the other concentrations of extract (60 and 40 mg/kg) exhibited peak disponea
of 80 and 60% at the 4th and 6th minute of exposure to histamine aerosols respectively. The
results obtained from the study suggested that methanolic extract of P. oleracea has an
insignificant bronchodilatory activity against histamine aerosols.
An study was carried out by using three different polyherbal formulations (Formulation 1, 2 and
3) by Patil and Burande[35]. The formulations were prepared as per the standard formulas of
Ayurvedic proprietary medicines and were tested for their antiasthmatic potency using passive
paw anaphylaxis in rats and histamine induced bronchoconstriction in guinea pigs. Three
different doses of each formulation i.e. 1000, 1500 and 2000 mg/kg were used during the study.
The result of the study showed that formulation 1 was found to be most effective and it showed
significant delay in the latency of dyspnea as compared to other two formulas. It also showed
dose dependent effects suggesting that the preparation is devoid of any interaction or side effects
even at large doses. The formulation 1 has not only delayed the latency but this ability was
sustained for a longer duration of time. The increased duration may be attributed to the
synergistic combinations of phytoconstituents.
Kristin et al[36] evaluated the safety and tolerability of a polyherbal formulation i.e., ASHMI
derived from a Traditional Chinese Medicine in adults subjects with allergic asthma.
Randomized, double-blind, placebo-controlled, dose escalation, phase- I trial was done under the
United States Food and Drug Administration Investigational New Drug title. Subjects received
one of three doses of ASHMI or placebo: 600 mg (2 capsules); 1200 mg (4 capsules); or 1800
mg (6 capsules) twice daily for 1 week. Four ASHMI and 2 placebo subjects were treated at each
dose level. Subjects continued to use their conventional asthma medications for the duration of
the study. In this study, ASHMI appeared to be safe and well tolerated.
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Ethanolic extract of leaves of Hiptage benghalensis was prepared and converted into formulated
dosage forms. Formulated dosage forms then subjected to evaluation of production quality by
different methods stated as per official compendia. The evaluated formulation were then
subjected to check for its efficacy by using experimental animal model like histamine and Ach
induced bronchoconstriction in guinea pigs. The formulated dosage forms exhibited significant
protection from histamine and Acetylcholine induced brocnchospasm when compared to control
group and is comparable to crude extract of Hiptage benghalensis and marketed antiasthmatic
product[37].
An herbal compound formulation Pentapala-04 prepared from five medicinal plants namely,
Adhatoda vasica, Ocimum sanctum, Coleus aromaticus, Glycyrrhiza glabra and Alpiania
galangal. The effect of “Pentapala-04” on ova albumin and aluminium hydroxide induced lung
damage in albino wistar rats was investigated. The rats were divided into three groups of four
animals each. Group I, II and III serves as control, toxic and post treatment group respectively.
The results showed that there was increased level of lipid peroxidation and decreased level of
antioxidants in toxic group animals. But the levels of antioxidant enzymes were restored in posttreated groups of animals, which might be due to the ability of Pentapala-04 to scavenge the
reactive oxygen species. Thus they demonstrated that ‘pentapala-04’ prevents ova albumin and
aluminum hydroxide induced oxidative stress, lung injury and inflammatory changes and can be
used as an antiasthmatic drug[38].
Shirishadi is an Ayurvedic polyherbal preparation used in Indian traditional medicine for the
treatment of Asthma and allergic disorders. The pharmacodynamic properties of ethanolic extract
of Shirishadi compound was evaluated on experimental model for its antihistaminic property
against H1 receptor and mast cell stabilizing property by Kajaria et al[39]. Significant increase in
preconvulsion time was observed on pretreatment with Shirishadi compound when the guinea
pigs were exposed to histamine. Demonstration of graded dose response of histamine and its
competitive antagonism on isolated perfused guinea pig ileum showed that it has specific
antagonism. The increasing dose of Shirishadi showed the Tachyphylaxis and receptor protection
response. Polyherbal formulation (500 μg and 1000 μg/ml) showed dose dependent significant
reduction in mast cell degranulation as compared to the compound 48/80 treated animals. The
result showed that the compound has antiasthmatic property by virtue of its bronchodilator, antihistaminic and mast cell stabilizing effect.
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The aqueous ethanol extracts of various traditional herbs like Adhatoda vasica, Acorus calamus,
Glyzyrrhiza glabra, Ocimum sanctum, Tylophora asthmatica, Piper longum and Solanum
xanthocarpum was evaluated for its antihistaminic activity by the inhibition of histamine induced
contractions on the guinea pig ileum. The results showed that the formulated cough syrup
inhibited histamine induced contractions of guinea pig ileum at 2.5 to 25 μg/ml concentrations in
a dose dependent manner and also significantly inhibited degranulation of mast cells[40].
Gohil et al[41] evaluated novel poly herbal formulations (PHE and LM-02) for asthma and related
conditions. The individual herbs were evaluated for their standard specification according to the
Ayurvedic Pharmacopoeia of India. PHE and LM-02 (an oral aerosol spray prepared from PHE)
were studied against allergen-induced bronchospasm using guinea pigs. The bronchospasm
studies indicated that these polyherbal formulations possess good bronchodilatory activity and
LM-02 produced better bronchodilatory effect than PHE. PHE and LM-02 might be considered
as cheaper and safer alternative for the treatment of bronchial asthma and related conditions.
The marine alga is always an important source of drugs and many useful drugs are directly
belonging to the marine sources. The marine algae Sargassum wightii have many
pharmacological activities. The antiasthmatic activity of leaf of Sargassum wightii and Adiantum
capillus was studied by Swaroop et al[42]. Ethanolic extracts of leaf of Sargassum wightii and
Adiantum capillus were prepared and the antiasthmatic activity was evaluated by experimental
models like histamine aerosol induced asthma in guinea pig. Animals treated with these extracts
showed significantly prolonged the latent period of convulsions as compared to control animals
when exposure of histamine aerosol. The histamine produced bronchial constriction in animal
model in histamine chamber. The ethanolic extract Adiantum capillus was more effective
comparatively to ethanolic extract Sargassum wightii.
A polyherbal preparation was set up by Tulsiani et al[43] with multi directing mechanisms
targeting on Asthma. The herbs used for the polyherbal preparation was Glycyrrhiza glabra,
Allium cepa and Clerrodendrum serratum. The preparation at 200 and 400 mg/kg were evaluated
for anti asthmatic activity. These herbs have expectorant, anti oxidant and anti inflammatory,
antihistaminic effects respectively which are in turn useful parameters against asthma. Guinea
pig tracheal chain proved helpful for evaluation of the efficacy of the preparation as compared to
other marketed Ayurvedic and allopathic medications. Also Broncho Alveolar Lavage fluid was
observed for eosinophilic and macrophage count estimation. Airway hyper responsiveness in
response to Methacholine administration proved beneficial for the study. This was further
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supported by lung tissue histology. Bronchial muscle relaxation was seen as well as
inflammation due to free radicals and cytokines exhibited a marked decline which displayed the
antiasthmatic potency of the polyherbal preparation.
A study was conducted by Shyamlal et al[44], 63 patients were administered with Shirishavaleha
(Herbal Ayurvedic Confection) at the dose of 10 g twice daily for 4 weeks with lukewarm water.
The results were assessed in terms of clinical recovery, symptomatic relief and pulmonary
function improvement. The effect of the treatment was assessed based on subjective and
objective parameters. A significant increase in PEFR, Hb and considerable decrease in absolute
eosinophil count (AEC) and E.S.R. were observed. From the study conducted, it was found that
21.15% (10) cases has shown marked improvement, 50.00 % (26) cases shown moderate
improvement, 19.23 % (10) cases shown mild improvement and 11.54% (06) of patients
remained unchanged. 11 cases were dropped out from the trial. The study revealed that current
herbal formulation can be used as an effective drug in bronchial asthma.
An investigation was undertaken by Kalpana et al[45] to evaluate the bronchodilator and antianaphylactic activity of the stem bark of Myrica sapida. Experimental models studied were
acetylcholine induced bronchospasm in guinea pigs, egg albumin induced anaphylaxis in guinea
pigs, in vitro studies on tracheal strip of egg albumin sensitized guinea pigs. Treatment with
ethanolic extract of M. sapida, (75 mg/kg, orally) resulted in significant protection against
acetylcholine aerosol induced bronchospasm and allergen induced anaphylaxis in guinea pigs.
The extract of M. sapida prevented the potentiation of responses and also produced a decrease in
pD2 value of histamine and acetylcholine in guinea pig tracheal strip. These results suggested that
M. sapida possesses bronchodilator activity, has potent inhibitory effect on immediate hypersensitivity reactions and decreases bronchial hyper responsiveness.
A clinical trial was conducted to detect the effect of an Ayurvedic herbal formulation Shatyadi
churna with and without Pranayama in the management of childhood asthma (Tamaka Shwasa)
by Aman et al[46]. After reaching to the diagnosis, patients were randomly distributed to three
groups, viz. Group-A received Shatyadi churna with warm water, Group-B received the same
with Pranayama and Group-C received the Placebo (Glucose in the dose of 2 gm in capsule
form) with Pranayama. The duration of the trial was two months and the patients were examined
after a gap of 15 days. The follow up period was of one month. The subjective and objective
parameters were measured before and after treatment in each group. The result of the Shatyadi
churna along with Pranayama was found to be highly significant in the study.
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In-vitro and in-vivo safety and anti-asthmatic activity of stem bark extracts of Prunus africana
and Warburgia ugandensis against induced asthma in BALB/c mice was studied by Karani et
al[47]. Efficacy against induced asthma was determined by assaying heart blood serum for
ovalbumin specific immunoglobulin E (IgE) antibodies and quantification of eosinophil
proportion in Bronchoalveolar lavage fluid (BALF). Eight sensitized groups were used, 2 were
controls, 3 were treated with P. africana extract and 3 with W. ugandensis; each treatment group
received one dose concentration of 125, 250 or 500 mg/kg body weight of either plant extracts.
The results showed that P. africana and W. ugandensis stem bark extracts have anti-asthmatic
property.
To determine the prevalence and pattern of use of complementary therapies in adults treated for
asthma in primary care in Singapore and the demographic and clinical factors associated with
their use a study was designed by Ng et al[48]. Five primary care clinics in Singapore were
selected for the study. Adult patients with asthma received a structured questionnaire interview
and clinical assessment that included demographic and clinical variables (clinical status, patient’s
knowledge, self-care and healthcare-seeking behaviour and spirometric measurements) and
detailed information on CAM use in the past one year. CAM use in the past year was reported by
27.2%, including animal food products (12.3%), herbs (10.3%), herbal-based proprietary
medicines (3.2%) and acupuncture or reflexology (1%). The use of CAM was significantly
associated with Chinese ethnicity, longer disease duration, moderate and severe persistent
asthma, lack of positive response to treatment in the past year, higher patient knowledge score,
and multiple sources of care providers. The use of CAM is highly prevalent in Asian patients
treated for asthma in primary care and was associated with cultural and clinical factors reflecting
a need to improve care.
A study was aimed by Gerda et al[49] to investigate the potential anti-inflammatory and immunemodulating properties of S. aethiopicus in vitro. The dried and powdered S. aethiopicus plant
material was extracted with organic solvents. The dried extracts were screened in vitro in the
transcription response, NF-κB and a cytokine assay. Significant activity was observed for the
extracts of the plant in these assays. This study provided that S. aethiopicus has antiinflammatory and immune-suppressing properties in vitro. These findings supported its
effectiveness against allergic asthma.
Adhatoda vasica have been used for the treatment of Shvasa roga in the traditional system and its
antiasthmatic property also revealed by various studies in recent years. Polyherbal formulation
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(containing mainly the ethanolic extract of Adhatoda vasica, Clerodendrum serratum, Curcuma
longa, Solanum xanthocarpum and Piper longum) was evaluated against compound 48/80induced mast cell degranulation as well as triple antigen-induced anaphylaxis in rats and results
suggested anti-anaphylactic and mast cell stabilizing property by Gohil et al[50].
The ethanolic extract of aerial parts of Aerva lanata was prepared and studied for its
antiasthmatic activity by Deepak et al[51]. The extracts exhibited significant dose dependent
antiasthmatic activity as revealed by its mast cell stabilization and inhibited the clonidine
induced catalepsy when evaluated in the isolated goat tracheal chain preparation model and invivo model using clonidine-induced catalepsy, mast cell degranulation in mice.
Methanolic extract of the stem barks of Ailanthus excelsa was prepared and evaluated in-vivo
and in-vitro screening models in Guinea pigs and revealed dose-dependent antiasthmatic activity
by Kumar et al[52].
Inula racemosa root extract was prepared by Gautam et al[53]. The dried extract was subjected for
its antiasthmatic activity by using suitable animal models. The results of the study revealed
antiasthmatic activity as noticed by antagonistic effect on histamine induced contraction, milkinduced eosinophilia and leukocytosis and protection against mast cell degranulation.
Methanolic extract of dried whole plant of Leucas aspera was prepared and screened for its
possible antiasthmatic activity by using different animal models by Limbasiya et al[54]. The
results of the study revealed the antiasthmatic activity in-vivo models like histamine induced
bronchospasm in guinea pigs, passive paw anaphylaxis in rats and milk induced eosinophilia
mice and in vitro model like mesentric mast cell degranulation by egg albumin etc.
Aerial parts of Onosma bracteatum showed antiasthmatic potential by decreasing the infiltration
of inflammatory mediators, inhibiting histamine release and decreasing airway inflammation in
vivo and in vitro experimental models[55].
The aqueous extract of Piper nigrum fruits was prepared and studied for its anti-asthmatic
potential by Parganiha et al[56]. The aqueous extract significantly inhibited acetylcholine induced
bronchoconstriction of isolated goat trachea which revealed its anti-asthmatic potential of the
fruits of Piper nigrum.
Ethanol extract of Woodfordia fruticosa dried flower showed bronchoprotective, bronchodilatory
and anti-inflammatory activity against experimental asthma induced by the combination of
histamine and acetylcholine aerosol in guinea pigs[57].
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The ethanol extract of the leaves of Alstonia scholaris inhibited the spontaneous movements of
rabbit jejunum and contractile effects of acetylcholine and histamine on guinea-pig ileum. The
extract also displayed marked reduction of barium chloride-, potassium chloride- and calcium
chloride-induced contraction on guinea pig ileum and pulmonary artery, implying a direct
interference of plant extract with the influx of calcium ions into cells. On the other hand, the
extract has no noticeable effect on mobilization of intracellular calcium. These results coupled
with the in vivo effects of ethanol extract make known that the Alstonia scholaris leaves
possessed broncho-vasodilatory activity mediated presumably by prostaglandins, calcium
antagonism and endothelium-derived relaxing factor[58].
Andrographolide is traditional Chinese herbal medicines possessed a strong anti-inflammatory
activity and has the potential to be used in allergic lung inflammation. Andrographolide could
inhibit extensive infiltration of inflammatory cells in lung and decrease airway hyper reactivity.
Andrographolide could inhibit NFkB expression in lung and suppress NF-kB translocation from
the cytoplasm to the nucleus of airway epithelial cells. Results bring in the anti-inflammatory
mechanisms of Andrographolide are associated with NF-kB expression in lung and suppress NFkB translocation from the cytoplasm to the nucleus of airway epithelial cells[59].
Euphorbia lunulata belongs to family Euphorbiaceae is found in the southeast of China. The
whole plants of E. lanulata have yielded kaempferol, quercetin, kaempferol 3-O-L-rhamnoside,
quercetin 3-O-L-hamnoside, 6,7-dihydroxycoumarin and maoyancaosu. It has long been used as
a traditional crude drug for the treatment of bronchial asthma and chronic bronchitis[60].
Gingko biloba is one of the most extensively used herbal medications in Europe. Standardized
extract of Gingko biloba (EGb), is sold under several different brand names: Ginkgobil, Rokan,
Tanakan, Tebonin and Kaveri. Ginkgo’s active ingredient, ginkgolide, antagonizes Platelet
Activating Factor (PAF) and may decrease airway inflammation. Ginkgo is also a commanding
antioxidant. Although Gingko biloba has a long history and a reasonable biochemical rationale,
one small pilot study has evaluated its effectiveness as an asthma remedy. That study found that
it has protective action against exercise-induced bronchospasm; it also decreased participants’
reactivity to house dust mite antigen[61].
Gyokuheifusan (GHS) is a usual formulation of Traditional Chinese Medicine (TCM) that is
usually prescribed to prevent or treat respiratory tract diseases, such as respiratory infection and
bronchial asthma. GHS down-regulates the over-production of IgE and IL-4 via a significant and
persistent increase of IFN-g. Yang et al found that Astragalus root (a core material of GHS)
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reduced the secretion of IL-4 by regulating the shift of Th1 to Th2, and the total IgE produced by
B cells decreased accordingly. GHS is commonly used to care for respiratory diseases in clinical
practice in oriental countries[62].
The anti-asthmatic activity of the extract of dried and fresh leaves, and the volatile and fixed oils
of Ocimum sanctum was evaluated against histamine and acetylcholine induced pre-convulsive
dyspnea (PCD) in guinea pigs. The extract of fresh leaves, volatile oil extracted from fresh
leaves and fixed oil from the seeds significantly protected the guinea pigs against histamine and
acetylcholine-induced PCD which showed its anti-asthmatic activity[63].
The fruits of Piper longum contain volatile oil, resin, alkaloids, piperine and piperlonguminine, a
waxy alkaloid Nisobutyldeca-trans-2-trans-4-dienamide and a terpenoid substance. The fruit
successfully reduce passive cutaneous anaphylaxis in rats and protect guinea pigs against antigen
induced bronchospasm; a 30% protection of mast cells was observed in an in vitro study by
Dahanukar et al[64].
The powdered rhizome of Hedychium spicatum given in divided doses of 10gm to 25 patients
with recurrent paroxysmal attacks of dyspnoea for 4 weeks (Bronchial asthma), completely
relieved dyspnoea, cough and restlessness in all patients. The bronchi completely disappeared in
36% of the patients. The mean R/R was reduced by 25% and the vital capacity increased by
20%. The mean absolute count also decreased by 55.6%[65,66].
CONCLUSION
Plants have always plays a commendable source of drugs; as a matter of fact many of the
currently available drugs in the market were derived either directly or indirectly from them. In
the last few decades, research has been focused on scientific evaluation and standardization of
traditional drugs of plant origin for their safety, efficacy and potency. More than 80% of
populations in the developing countries are using traditional medicines for their primary health
care. Over the past few decades, there have been significant scientific advances leading to
improved understanding and management of asthma. The current systems of conventional
therapy do not cure the disorder but can control the symptoms. Thus there is a need to walk
around safe alternative therapies, such as herbal medicines, so that they can be successfully
incorporated along with conventional therapy to provide utmost benefits to the patients suffering
from asthma. The research for alternate remedies for asthma will continue all over the world as
the disease acquire several challenges not only to the physician but also to the researchers.
Inadequate numbers of clinical trials have been conducted till date. Further studies in this track
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are to be expected to result in novel additions to modern therapeutics. The present review
highlighted need for more research in effectiveness of herbal medicine in bronchial asthma. As a
large number of experimental studies have documented the presence of antiasthmatic properties
in various medicinal plants, there is budding for discovering new compounds helpful in the
management of asthma. Attempt should be made to develop polyherbal formulations which
contain various herbs valuable for prophylaxis as well as for the treatment of asthma.
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For Correspondence
C. S. Barik
Email: [email protected]
Barik et al. / Pharma Science Monitor 5(2), Apr-Jun 2014, 73-94

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