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ASHWAGANDHA: NATURE"S BOON FOR A HEALTHY LIFE

Article in World Journal of Pharmaceutical Research · January 2018

DOI: 10.20959/wjpr201818-13593

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 World Journal of Pharmaceutical Research
Sahu et al. SJIF Impact
World Journal of Pharmaceutical Factor 8.074
Research
Volume 7, Issue 18, 598-612. Review Article ISSN 2277–7105

ASHWAGANDHA: NATURE”S BOON FOR A HEALTHY LIFE

Dr. Shrawan Kumar Sahu1*, Dr. Ashok Kumar Sinha2 and Dr. Rahul Ghuse3

Research Officer (Ayu.), Regional Ayurveda Research Institute, Gangtok, Sikkim, India,
737102.

Article Received on
ABSTRACT
02 Sept. 2018, Attitude, behavior, concentration, dedication and enthusiasm are very
Revised on 24 Sept. 2018,
Accepted on 15 October 2018 much necessary for the continuation and successful completion of any
DOI: 10.20959/wjpr201818-13593 task. Owing to day by day decline of these qualities, masses are in
search of a safe agent which can help them in leading happy lives
*Corresponding Author through accomplishment of their works smoothly. Ashwagandha is
Dr. Shrawan Kumar Sahu very much capable of meeting this demand of the people. It is
Research Officer (Ayu.), classified as a Rasayana (rejuvenation-medicine) and accepted to
Regional Ayurveda Research
increase longevity and vitality. The drug is reported with anti-
Institute, Gangtok, Sikkim,
inflammatory, anti-arthritic, caridioprotective, anti-stress, tranquillizer-
India-737102.
like sedative activity, hypoglycemic, thyroprotective activity and
proved to be an effective remedy in the malignant growth of different organs. Although many
articles have been published on this wonderful drug, the holistic approach has not been
addressed till date. This article is for serving that very purpose. The review includes various
activities of Ashwagandha in experimental models along with clinical evaluation of the drug
in various dosage forms. Thorough review of various books, scientific research journals,
theses, articles etc. available on Ashwagandha along with internet was performed to bring
about the article in present form. The classical literatures in Ayurveda, Unani & Allopathy on
this natural gift were studied at fundamental level, interpreted and analyzed logically and are
presented in this detail research article.

KEYWORDS: Ashwagandha, Rasayana, Ayurveda.

INTRODUCTION
Ashwagandha (Withania somnifera) has been an important herb in the Ayurvedic and
indigenous medical systems for over 3000 years. The roots of the plant are categorized as
Rasayana i.e. having capability to promote health and longevity by augmenting defense

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against disease, arresting the ageing process, revitalizing the body in debilitated conditions,
increasing the capability of the individual to resist adverse environmental factors and by
creating a sense of mental wellbeing.[1] It is in use for a very long time for all age groups and
both sexes and even during pregnancy without any side effects.[2] The pharmacological
effects of the roots of Ashwagandha are attributed to the presence of withanolides, a group of
steroidal lactones.[3] Its leaves are used in Ayurvedic and Unani systems for treatment of
tumors and tubercular glands.[4] A number of withanolide steroidal lactones have been
isolated from the leaves of Withania somnifera[5] and these exhibit antibacterial, anti-fungal
and antitumor properties.[6]

Ashwagandha (Withania somnifera) is one of the most revered plants in traditional Ayurvedic
medicine in India. It is an erect, grayish, subshrub with inconspicuous yellow or greenish
flowers followed by small, spherical, orange-red berries containing yellow, kidney-shaped
seeds. It grows three-to-five feet tall, mainly on waste land, but is cultivated widely as the
whole plant; most commonly the root and leaf are used medicinally.[7,8]

The importance of this wonder drug cannot be overemphasized, since there are WITHANIA
somnifera standards monographs published in the Ayurvedic Pharmacopoeia of India (Vol. I,
1989)[9], Siddha Pharmacopoeia of India (Vol. I, 2008)[10], Unani Pharmacopoeia of
India (Vol. I, 2007)[11], the World Health Organization (WHO) Monographs (Vol. 4, 2009) [12]
as well as in the currently valid editions of the British Pharmacopoeia(BP 2012)[13], Indian
Pharmacopoeia (IP 2010)[14] and United States Pharmacopeia (USP 36).[15]

The species is widely distributed in the northwestern Indian states of Gujarat, Madhya
Pradesh, Maharashtra, Rajasthan, Uttar Pradesh, and the Punjab plains extending to the
mountainous regions of Himachal Pradesh and Jammu. [16] It also is cultivated in parts of
Madhya Pradesh and Rajasthan.[17] Northwest of India, its habitat extends into the Pakistani
provinces of Sindh and Baluchistan, and on into Afghanistan. To the southeast of India, it
occurs in Sri Lanka.[18]

Preparations of various plant parts have been credited with the following actions:
abortifacient, adaptogenic, alterative, analgesic, antiarthritic, antiasthmatic, antibiotic,
antidyspeptic, anti-inflammatory, antimitotic, antiproliferative, antitumor, aphrodisiac,
astringent, bactericide, carminative, contraceptive, depurative, diuretic, emetic, febrifuge,
fungicidal, hypnotic, immune-modulating, laxative, proteolytic, tonic, and nervine

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sedative.[19,20,21] Additionally, it may have cytotoxic, chemopreventative, and radiosensitizing

actions.[20]

Some herbalists refer to Ashwagandha as Indian ginseng, since it is used in Ayurvedic

medicine in a way similar to that ginseng is used in traditional Chinese medicine. Studies
have proven that the activity of the Withania extract was approximately equal to the activity
of the Panax ginseng extract. Withania somnifera, owever, has an advantage over Panax
ginseng in that it does not appear to result in ginseng- abuse syndrome, a condition
characterized by high blood pressure, water retention, muscle tension, and insomnia.[22]

Major Chemical Constituents

Phytochemical contents: Ashwagandha has been found to contain steroidal lactones called
withanolides. Much of the pharmacological activities are attributed to the presence of these
steroidal lactones.[23] In addition, the roots provide 18 fatty acids, beta-sitesterol, polyphenols
and phytosterols. The root contains several alkaloids, including withanine, withananine,
withananinine, pseudo-withanine, somnine, somniferine, somniferinine. The leaves of Indian
chemotype contain withanolides, including withaferin A.[24] Withanine is sedative and
hypnotic. The root extract contains an ingredient which has GABA mimetic activity. The free
amino acids present in the root include aspartic acid, glycine, tyrosine, alanine, proline,
tryptophan, glutamic acid and cystine.[25]

Steroidal compound: These include withaferin A, Withanolides G&D sitoindosides IX&X

and withasomnine. These have been reported as active marker for standardization.[26]
Withaferin A, a steroidal lactone is the most important withanolide isolated from the extract
of the leaves and dried roots of Withania somnifera. Anti-inflammatory activity has been
attributed to biologically active steroids, of which withaferin A is a major component. The
activity is comparable to that of hydrocortisone sodium succinate. Withaferin A also showed
significantly protective effect against CCl4 induced hepatotoxicity in rats. It was as effective
as hydrocortisone dose. The curative properties of the leaves and roots are attributed to
Withaferin A. Withaferin A is antitumour, antiarthritic and antibacterial.

Adaptogenic effect: Double blind clinical trial involving 60 healthy children (8-12 years
age), oral intake of 2 g/day of root powder (in 100 ml milk) for 2months lead to increase
body weight, total protein and Mean corpuscular hemoglobin. There was no toxic effect of
any kind even after 8 months of daily consumption.[76] In a related clinical study, root

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powder (3 gms. /day) was given to healthy male volunteers (age 50-59 years) for one year.
There was a uniform significant increase in Hb, RBC improvement in hair melanin and
seated stature.[27]

In a double-blind clinical trial, Ashwagandha root powder was tested in a group of 101
healthy males, 50-59 years old, at a dosage of 3 grams daily for one year. A significant
improvement in haemoglobin, red blood cell count, hair melanin, and seated stature was
observed. Serum cholesterol decreased and nail calcium was preserved. ESR decreased
significantly and 71.4 percent reported improvement in sexual performance.[28]

In a double blind study shade dried roots of WS were powdered and made as tablets of 0.5
gms each and administered in the dose of 2 tabs 3 times a day with milk to healthy volunteers
for a period of one year. Results have shown significant increase in haemoglobin, RBC, Hair
melanin, and in seated stature in the treated group as compared to control group. Serum
cholesterol and calcium level of nails have also been decreased in treated group.[29]

Anti-inflammatory Activity
Withaferin A exhibits fairly potent anti-arthritic and anti-inflammatory activities. Anti-
inflammatory activity has been attributed to biologically active steroids, of which Withaferin
A is a major component. It is as effective as hydrocortisone sodium succinate dose for
dose.[30] It was found to suppress effectively arthritic syndrome without any toxic effect.
Unlike hydrocortisone-treated animals which lost weight, the animals treated with Withaferin
A showed gain in weight in arthritic syndrome. It is interesting that Withaferin A seems to be
more potent than hydrocortisone in adjuvant-induced arthritis in rats, a close experimental
approximation to human rheumatoid arthritis. In its oedema inhibiting activity, the compound
gave a good doseresponse in the dose range of 12-25 mg/kg body weight of Albino rats
intraperitoneally and a single dose had a good duration of action, as it could effectively
suppress the inflammation after 4 hours of its administration.[31] Asgand (Withania somnifera)
has been shown to possess anti-inflammatory property in many animal models of
inflammations like carrageenan-induced inflammation, cotton pellet granuloma and adjuvant-
induced arthritis Detailed studies were carried out to investigate the release of serum β-1
globulin during inflammation by two models of inflammations viz. primary phase of
adjuvantinduced arthritis and formaldehyde-induced arthritis. The experiments showed
interesting results as most of the APR wereinfluenced in a very short duration and also
suppressed the degree of inflammation.[32]

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Analgesic effect
This study was done to evaluate the analgesic effect and tolerability of single oral dose
(1000mg) of standardized aqueous extract of Withania somnifera using Hot Air Pain model
in healthy human volunteers as per ICH GCP Guidelines. Subjects were randomised to
receive either single oral dose of 1000mg standardize aqueous extract of Withania somnifera
or identical placebo in a double blind manner. Mean Pain Threshold Time at baseline and
3hrs after drug administration were noted. Washout period of 10-14 days was given for cross-
over between the two treatments. Safety assessments were conducted before and at end of
study in total twelve subjects were enrolled. In the study, treatment with standardized
aqueous extract of Withania somnifera produced significant increase in Pain Threshold time
compared baseline and placebo.[33]

Rejuvenating Effect
A double-blind, placebo-controlled study was conducted to evaluate the efficacy an ethanolic
extract of Aswagandha (Withania somnifera), in patients with ICD-10 anxiety disorders
comprised 39 subjects, of whom 20 received the drug and 19 received placebo. At 6 weeks,
significantly more patients met a priori response criteria in the drug group (88.2%) as
compared with the placebo group (50%). Results indicated that ethanolic extract has useful
anxiolytic potential.[34]

Antistress effect
The safety and efficacy of a high-concentration full-spectrum extract of Ashwagandha roots
to reduce stress and anxiety was studied on 64 subjects for 60 days with prospective, double-
blind, randomized, placebo-controlled design. In the study drug treatment group, each
capsule contained 300 mg of high-concentration full-spectrum extract from the root of the
Ashwagandha. The treatment group exhibited a significant reduction (P<0.0001) in scores on
all the stress-assessment scales compare to the placebo group. The serum cortisol levels were
substantially reduced (P=0.0006) in the Ashwagandha group, relative to the placebo group.
The study suggest that a high-concentration full-spectrum Ashwagandha root extract safely
and effectively improves an individual’s resistance towards stress and thereby improves self-
assessed quality of life.[35]

In another clinical trial, the effect of standardized WS root and leaf extract (WSE) was
evaluated in chronically stressed humans Participants who were randomly assigned to WSE
(125 mg QD, 125 mg BD, or 250 mg BID) or placebo groups. Stress levels were assessed at

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days 0, 30 and 60 using a modified Hamilton anxiety (mHAM-A) scale. Biochemical and
clinical variables were measured at days 0 and 60. 130 subjects enrolled 98 completed the
study. Between days o and 60 the WSE 125 mg QD group decreased significantly more than
placebo for mean mHAM- A score, serum cortisole, serum C-reactive protein, pulse rate and
blood pressure. The consumption of WSE significantly reduces experiential and biochemical
reduction of stress without adverse effects.[36]

A study conducted by the Institute of Basic Medical Sciences at Calcutta University

examined the effects of Ashwagandha on chronic stress in rodents. For a period of 21 days,
the animals received a mild electric shock to their feet. The resulting stress on the animals
produced hyperglycemia, glucose intolerance, increase in plasma corticosterone levels,
gastric ulcerations, male sexual dysfunction, cognitive deficits, immunosuppression and
mental depression.[37] Researchers using Withania somnifera discovered the animals given the
herb an hour before the foot shock experienced a significantly reduced level of stress. This
research confirms the theory that Ashwagandha has a significant anti-stress effect.[38]

Cardiovascular protection
Withania somnifera may be useful as a general tonic, due in part to its beneficial effects on
the cardiopulmonary system, as reported in the following studies. The effect of WS was
studied on the cardiovascular and respiratory systems in dogs and frogs.[39] The alkaloids had
a prolonged hypotensive, bradycardiac, and respiratory stimulant action in dogs. The study
found that the hypotensive effect was mainly due to autonomic ganglion blocking action and
that a depressant action on the higher cerebral centers also contributed to the hypotension.
The alkaloids stimulated the vasomotor and respiratory centers in the brain stem of dogs. The
cardio-inhibitory action in dogs appeared to be due to ganglion blocking and direct
cardiodepressant actions. The alkaloids produced immediate predominant but short-lived
cardio-depressant effects and a weak but prolonged cardiotonic effect in isolated normal and
hypodynamic frog hearts. In another study, Left ventricular dysfunction was seen as a
decrease in heart rate, left ventricular rate of peak positive and negative pressure change and
elevated left ventricular end-diastolic pressure in the control group was recorded. Withania
somnifera showed strong cardioprotective effect in the experimental model of isoprenaline-
induced myonecrosis in rats. Augmentation of endogenous antioxidants, maintenance of the
myocardial antioxidant status and significant restoration of most of the altered
haemodynamic parameters may contribute to its cardioprotective effect.[40]

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Hypoglycemic and hypocholesterolemic effect

In a study, hypoglycemic, diuretic and hypocholesterolemic effects of roots of Withania
somnifera were assessed on human subjects. Six mild NIDDM subjects and six mild
hypercholesterolemic subjects were treated with the powder of roots of WS for 30 days.
Suitable parameters were studied in the blood and urine samples of the subjects along with
dietary pattern before and at the end of treatment period. Decrease in blood glucose was
comparable to that of an oral hypoglycemic drug. Significant increase in urine sodium, urine
volume, significant decrease in serum cholesterol, triglycerides, LDL (low density
lipoproteins) and VLDL (very low density lipoproteins) cholesterol were observed indicating
that root of WS is a potential source of hypoglycemic, diuretic and hypocholesterolemic
agents.[41]

Anti-carcinogenic activity
Ashwagandha is reported to have anti-carcinogenic effects. Research on animal cell cultures
has shown that the herb decreases the levels of the nuclear factor kappaB, suppresses the
intercellular tumor necrosis factor, and potentiates apoptotic signalling in cancerous cell
lines.[42] In one study, the herb was evaluated for its anti-tumor effect in urethane-induced
lung tumors in adult male mice.[43] Following administration of Ashwagandha over a period
of seven months, the histological appearance of the lungs of animals which received the herb
was similar to those observed in the lungs of control animals.

Anti-tumor effect Effect on Chinese Hamster Ovary (CHO) cells carcinoma

Withania roots caused the inhibitory effect of about 49% on colony forming efficiency of
CHO cells. It inhibits the cell growth and prevents the cell attachment. It induced long term
growth inhibition of CHO cells which was dependent on the cell density and duration of
Ashwagandha exposure.[44]

Adjuvant to chemotherapy
Fifty patients were recruited to each group, with a median age of 51 years (range 36–70
years) in the WITHANIA somnifera plus chemotherapy group and 50.5 years (range 30–82
years) in the control group. Eight patients had stage I, 33 stage II, 44 stage III, and 15 stage
IV breast cancer. Fifteen patients were offered palliative chemotherapy and 85 were offered
adjuvant chemotherapy. Patients in the group treated with WITHANIA somnifera root extract
and chemotherapy had less fatigue than did those in the control group (PFS p < 0.001 and
SCFS p < 0.003). QoL was significantly better (p = 0.0001) than in the control group. There

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was no difference in the haematological parameters or 24-month overall survival for all
stages [study 74% versus control 56% (p = 0.174)]; however, there was a trend for longer
survival in the patients treated with WITHANIA somnifera root extract plus chemotherapy.
Addition of WITHANIA somnifera to chemotherapy could have a positive effect on fatigue
and improve QoL in patients with breast cancer. The effectiveness and toxicity of
chemotherapy were not altered. Thus further study with a large sample size, uniform tumour
criteria, and risk stratified patients with breast cancer could help to validate our preliminary
outcome.[45]

Effect on neurodegenerative diseases such as Parkinson's, Huntington's and

Alzheimer's diseases-In patients with Alzheimer's disease, neuritic atrophy and synaptic
loss[46] are considered the major causes of cognitive impairment, as based on the results of
neuropathological post-mortem studies of the brain.[47] In the brains of patients suffering from
other neurodegenerative diseases such as Parkinson's disease, Huntington's disease, and
Creutzfeldt- Jakob disease, the atrophy of neurites has also been observed as a significant part
of the etiology. There are dozens of studies that show that Ashwagandha slows, stops,
reverses or removes neuritic atrophy and synaptic loss. Therefore Ashwagandha can be used
to treat Alzheimer's, Parkinson's, Huntington's and other neurodegenerative diseases at any
stage of the disease, even before a person has been diagnosed and is still in the state of mild
forgetfulness, etc. Glycowithanolides withaferin- A and sitoindosides VII–X isolated from
the roots of Ashwagandha significantly reversed ibotenic acid induced cognitive defects in
Alzheimer's disease model.[48]

GABA-mimetic effect on neurodegeneration and neuroregenerative potential

Behavioral experiments have lent support to the GABA-mimetic activity of Ashwagandha
root extract. GABAergic neurodegeneration due to neuroleptic-induced excitotoxicity and
oxidative stress is one of the etiopathological mechanisms in the pathophysiology of tardive
dyskinesia[49] and GABA agonists are shown to be effective in ameliorating the symptoms of
tardive dyskinesia. The beneficial effect of Ashwagandha root extract might be due to its
GABA mimetic activity. Ashwagandha, its constituents and the metabolites of its constituents
promote the growth of nerves after taking it for 7 days.

An intriguing study demonstrated that chronic oral administration of withanoside IV

attenuated the axonal, dendritic and synaptic losses and memory deficits induced by amyloid
peptide Aβ(25–35) in mice 21.[50] After oral administration in mice, withanoside IV was

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metabolized into sominone, which induced marked recovery in neurites and synapses and
also enhanced axonal and dendritic outgrowth and synaptogenesis. These effects were
maintained for at least 7 days after discontinuing withanoside IV administration. These data
suggest that withanoside IV, and its metabolite, sominone, may have clinical usefulness as
antidementia drugs.

Immunomodulatory Activity
Asgand showed a significant modulation of immune reactivity in animal models.
Administration of Asgand was found to prevent myelo-suppression in mice treated with three
immunosuppressive drugs viz. cyclophosphamide, azathioprin, and prednisolone. Treatment
with Asgand was found to significantly increase Hb concentration, RBC count, platelet count,
and body weight in mice.[51] Administration of Asgand extract was found to significantly
reduce leucopenia induced by cyclophosphamide (CTX) treatment. Administration of Asgand
extract increased the number of β-esterase positive cells in the bone marrow of CTX treated
animals, compared to the CTX alone treated group.[52] Administration of Asgand extract was
found to significantly reduce leucopenia induced by sub-lethal dose of gamma radiation.[52]
Withaferin A and Withanolide E exhibited specific immunosuppressive effect on human B
and T lymphocytes and on mice thymocytes. Withanolide E had specific effect on T
lymphocytes whereas Withaferin A affected both B and T lymphocytes.[53]

The growth-promoting effect

The growth-promoting effect of WS was studied for 60 days in a double-blind study of 60
healthy children, age 8-12 years, who were divided into five groups of 12. Group 1 was given
purified and powdered WS 2 g/day fortified in 100 cc of milk (no details about purification
and powdering methods were disclosed). Similarly, Group 2 received 2 g daily of a mixture
of equal parts WS and Punarnava (Boerhaavia diffusa), Groups 3 and 4 were given ferrous
fumarate 5 mg/day and 30 mg/day, respectively, and Group 5 received placebo. Group 1
experienced a slight increase in haemoglobin, packed cell volume, mean corpuscular volume,
serum iron, body weight, and hand grip, and significant increases in mean corpuscular
haemoglobin and total proteins (p<0.01) at the end of 60 days when compared to the initial
level and the placebo group. Group 2, treated with WS and Punarnava, showed a significant
increase in the level of haemoglobin at the end of 30 days compared to the initial value.
Marked increases in the levels of haemoglobin, packed cell volume, mean corpuscular
volume, mean corpuscular haemoglobin, serum iron, and hand grip were also observed at the

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end of 60 days when compared to initial levels. It was noted that 13 of 15 children had an
increase in body weight, 10 children had an increase in haemoglobin and packed cell volume,
and 11 children had an increase in serum iron. The study demonstrated that WS may be
useful as a growth promoter and hematinic in growing children.[54]

Anti-arthritic effect
In a double-blind, placebo-controlled cross-over study, 42 patients with osteoarthritis were
randomized to receive a formula containing Ashwagandha (Ashwagandha, turmeric,
boswellia and zinc complex) or placebo for three months. The herbal formula significantly
reduced the severity of pain (p<0.001) and disability (p<0.05) scores, although no significant
changes in radiological appearance or SED (Erythrocyte sedimentations) rate were noted.[55]

Rasayana effect: Randomized Placebo-Controlled Adjunctive Study of an Extract of

Withania somnifera for Cognitive Dysfunction in Bipolar Disorder was assessed. Sixty
euthymic subjects with DSM-IV bipolar disorder were enrolled in an 8-week, double-blind,
placebo-controlled, randomized study of WSE (500 mg/d) as a precognitive agent added
adjunctively to the medications being used as maintenance treatment for bipolar disorder.

Fifty-three patients completed the study (WSE, n = 24; placebo, n = 29). Compared to
placebo, WSE provided significant benefits for 3 cognitive tasks: digit span backward (P =
.035), Flanker neutral response time (P = .033), and the social cognition response rating of
the Penn Emotional Acuity Test (P = .045). Mood and anxiety scale scores remained stable,
and adverse events were minor. In preliminary level, WSE appears to improve auditory-
verbal working memory (digit span backward), a measure of reaction time, and a measure of
social cognition in bipolar disorder. Given the paucity of data for improving cognitive
capacity in bipolar disorder, WSE offers promise, appears to have a benign side-effects
profile, and merits further study.[56]

Drug Interactions: Withania somnifera given in combination with a diazepam produces an

additive effect. The combination when used in status epilepticus was able to reduce
significantly the effective dose of diazepam to offer complete protection with no subsequent
mortality. Administration of Withania somnifera markedly alters the plasma levels and
pharmacokinetics of Amikacin resulting in the modification of the dosage regimen of
Amikacin in healthy buffalo calves which clearly indicated their safe and effective
therapeutic use with promising antimicrobial polypharmacy.[57]

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Immunopotentiation on oral feeding of standardized aqueous extract of Withania somnifera

(Linn. Dunal, Family Solanaceae) was evaluated in laboratory animals immunized with DPT
(Diphtheria, Pertussis, Tetanus) vaccine. Reduced mortality accompanied with overall
improved health status was observed in treated animals after intracerebral challenge of B.
pertussis indicating development of protective immune response. Present study indicates
application of the test material as potential immunopotentiating agent possible applications in
immunochemical industry. The test material also offers direct therapeutic benefits resulting in
reduced morbidity and mortality of experimental animals.[58]

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