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A Review on Pharmacological Profile of Withania somnifera (Ashwagandha).

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Abstract

Withania somnifera (Ashwagandha) is a plant used in medicine from the time of Ayurveda, the ancient system of Indian medicine. The dried roots of the plant are used in the treatment of nervous and sexual disorders. this review article is presented to compile all the updated information on its phytochemical and pharmacological activities, which were performed by widely different methods. Studies indicate ashwagandha possesses antioxidant, anxiolytic, adaptogen, memory enhancing, antiparkinsonian, antivenom, antiinflammatory, antitumor properties. Various other effects like immunomodulation, hypolipidemic, antibacterial, cardiovascular protection, sexual behaviour, tolerance and dependence have also been studied. These results are very encouraging and indicate this herb should be studied more extensively to confirm these results and reveal other potential therapeutic effects. Clinical trials using ashwagandha for a variety of conditions should also be conducted.
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Research and Reviews: Journal of Botanical Sciences
A Review on Pharmacological Profile of Withania somnifera (Ashwagandha).
Kaur Narinderpal1*, Niazi Junaid2, and Bains Raman3
1Baddi University of Emerging Sciences and Technology, Makhnumajra, Baddi - 173205, Himachal Pradesh, India.
2Bahra Institute of Pharmacy, Patiala - 147001, Punjab, India.
3Grecian Superspeciality Hospital, Sector-69, SAS Nagar, Mohali, Punjab, India.
Review Article
Received: 07/08/2013
Revised: 17/09/2013
Accepted: 01/10/2013
*For Correspondence
Baddi University of Emerging
Sciences and Technology,
Makhnumajra, Baddi - 173205,
Himachal Pradesh, India.
Keywords: Withania somnifera,
Withanolides, Pharmacological
activities.
ABSTRACT
Withania somnifera (Ashwagandha) is a plant used in medicine from
the time of Ayurveda, the ancient system of Indian medicine. The dried roots
of the plant are used in the treatment of nervous and sexual disorders. this
review article is presented to compile all the updated information on its
phytochemical and pharmacological activities, which were performed by
widely different methods. Studies indicate ashwagandha possesses
antioxidant, anxiolytic, adaptogen, memory enhancing, antiparkinsonian,
antivenom, antiinflammatory, antitumor properties. Various other effects like
immunomodulation, hypolipidemic, antibacterial, cardiovascular protection,
sexual behaviour, tolerance and dependence have also been studied. These
results are very encouraging and indicate this herb should be studied more
extensively to confirm these results and reveal other potential therapeutic
effects. Clinical trials using ashwagandha for a variety of conditions should
also be conducted.
INTRODUCTION
Withania somnifera (WS), also known as ashwagandha, Indian ginseng, and winter cherry, it has been an
important herb in the Ayurvedic and indigenous medical systems for over 3000 years. The roots of the plant are
categorised as rasayanas, which are reputed to promote health and longevity by augmenting defence against disease,
arresting the ageing process, revitalising 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 WS 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 W. somnifera [5]. and exhibit antibacterial, anti-fungal and antitumor
properties [6]. Ashwagandha is used to calm the mind, relieve weakness and nervous exhaustion, build sexual energy
and promote healthy sleep. The herb is termed a rasayana. in Ayurvedic practice, which means it acts as a tonic for
vitality and longevity. It is also classified as an adaptogen [7]. Two varieties of Asgand have been mentioned in classical
Unani literatue: 1) Asgand Nagori and 2) Asgand Dakani. Asgand Nagori is preferred for its more potential medicinal
properties [8].
Taxonomical Classification
Kingdom : Plantae, Plants;
Subkingdom : Tracheobionta, Vascular plants;
Super division : Spermatophyta, Seeds plants;
Division : Angiosperma
Class : Dicotyledons
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Order : Tubiflorae
Family : Solanaceae
Genus : Withania
Species : somnifera Dunal
Botanical Description
WS is a small, woody shrub in the Solanaceae family that grows about two feet in height. It can be found
growing in Africa, the Mediterranean, and India. An erect, evergreen, tomentose shrub, 30-150 cm high, found
throughout the drier parts of India in waste places and on bunds. Roots are stout fleshy, whitish brown; leaves simple
ovate, glabrous, those in the floral region smaller and opposite; flowers inconspicuous, greenish or lubrid-yellow, in
axillary, umbellate cymes; berries small, globose, orange-red when mature, enclosed in the persistent calyx; seeds
yellow, reniform. The roots are the main portions of the plant used therapeutically. The bright red fruit is harvested in
the late fall and seeds are dried for planting in the following spring.Parts used: Whole plant, roots, leaves, stem, green
berries, fruits, seeds, bark are used.
Chemical Composition
Laboratory analysis has revealed over 35 chemical constituents contained in the roots of Withania somnifera
[9]. The biologically active chemical constituents are alkaloids (isopellertierine, anferine), steroidal lactones
(withanolides, withaferins), saponins containing an additional acyl group (sitoindoside VII and VIII), and withanoloides
with a glucose at carbon 27 (sitonidoside XI and X). Withania somnifera is also rich in iron. The roots of Withania
somnifera consist primarily of compounds known as withanolides, which are believed to account for its extraordinary
medicinal properties. Withanolides are steroidal and bear a resemblance, both in their action and appearance, to the
active constituents of Asian ginseng (Panax ginseng) known as ginsenosides. Ashwagandha's withanolides have been
researched in a variety of animal studies examining their effect on numerous conditions, including immune function
and even cancer [10]. Chemical analysis of Ashwagandha show its main constituents to be alkaloids and steroidal
lactones. Among the various alkaloids, withanine is the main constituent. The other alkaloids are somniferine, somnine,
somniferinine, withananine, pseudo-withanine, tropine, pseudo-tropine, 3-a-gloyloxytropane, choline, cuscohygrine,
isopelletierine, anaferine andanahydrine. Two acyl steryl glucoside viz. sitoindoside VII and sitoindoside VIII have been
isolated from root. The leaves contain steroidal lactones, which are commonly called withanolides. The withanolides
have C28 steroidal nucleus with C9 side chain, with a six membered lactone ring [11]. Twelve alkaloids, 35 withanolides,
and several sitoindosides from Withania somnifera have been isolated and studied. Asitoindoside is a withanolide
containing a glucose molecule at carbon 27. Much of Ashwaganda's pharmacological activity has been attributed to two
main withanolides, withaferin A and withanolide D. Further chemical analysis has shown the presence of the following:
Anaferine (Alkaloid), Anahygrine (Alkaloid), Beta-Sisterol, Chlorogenic acid (in leaf only), Cysteine (in fruit), Cuscohygrine
(Alkaloid), Iron, Pseudotropine (Alkaloid), Scopoletin, Somniferinine (Alkaloid), Somniferiene (Alkaloid), Tropanol
(Alkaloid), Withanine (Alkaloid), Withananine (Alkaloid) and Withanolides A-Y(Steroidal lactones)[ 12,13].
Pharmacological Activity
Centuries of Ayurvedic medical experience using Withania somnifera have revealed it to have pharmacological
value as an adaptogen, antibiotic,
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aboritifacient, aphrosidiac, astringent, antiinflammatory, deobstruent, diuretic, narcotic, sedative, and tonic.
Ashwagandha has been found to: Provide potent antioxidant protection [14,15]. Stimulate the activation of immune
system cells, such as lymphocytes and phagocytes [16,17]. Counteract the effects of stress and generally promote
wellness [18].
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 [19]. 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 [20]. 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 [21].
Anti-stress
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 [22]. 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 adaptogenic effect [23]. Research conducted at the Department of Pharmacology, University of
Texas Health Science Center indicated that extracts of Ashwagandha produce GABA-like activity, which may account for
the herb's anti-anxiety effects [24]. GABA (Gamma Amino-butyric acid) is an inhibitory neurotransmitter in the brain. Its
function is to decrease neuron activity and inhibit nerve cells from over firing. This action produces a calming effect.
Excessive neuronal activity can lead to restlessness and insomnia, but GABA inhibits the number of nerve cells that fire
in the brain, and helps to induce sleep, uplift mood, and reduce anxiety. Ashwagandha has traditionally been used to
stabilize mood in patients with behavioral disturbances. Research has revealed that the herb produces an anti-
depressant and anti-anxiety effect in rodents comparable to the anti-depressant drug imipramine and the anti-anxiety
drug lorazepam (Ativan) [25]. In fact, Ashwagandha is one of the most widespread tranquillizers used in I ndia, where it
holds a position of importance similar to ginseng in China. It acts mainly on the reproductive and nervous systems,
having a rejuvenative effect on the body, and is used to improve vitality and aid recovery after chronic illness [26].
Chronic stress can cause conditions such as cognitive deficit, immunosuppression, sexual dysfunction, gastric
ulceration, irregularities in glucose homeostasis, and changes in plasma corticosterone levels. In a rat model of chronic
stress syndrome, Withania somnifera and Panax ginseng extracts were compared and contrasted for their abilities to
relieve some some of the adverse effects of chronic stress [2 7]. Research results showed that both Ashwagandha and
Panax ginseng decreased the frequency and severity of stress-induced ulcers, reversed stress-induced inhibition of
male sexual behavior, and inhibited the effects of chronic stress on retention of learned tasks. Both botanicals also
reversed stress-induced immunosuppression, but only the Withania extract increased peritoneal macrophage activity.
The activity of the Withania extract was about the same as the activity of the ginseng extract. Withania somnifera,
however, 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 [2 8].
Antibiotic Activity
The antibiotic activity of the roots as well as leaves has recently been shown experimentally. Withaferin A in
concentration of 10µg/ml inhibited the growth of various Gram-positive bacteria, acid-fast and aerobic bacilli, and
pathogenic fungi. It was active against Micrococcus pyogenes var aureus and partially inhibited the activity of Bacillus
subtilis glucose-6-phosphatedehydrogenase. Withaferin A inhibited Ranikhet virus. The shrub’s extract is active against
Vaccinia virus and Entamoeba histolytica [29]. Asgand showed the protective action against systemic Aspergillus
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infection. This protective activity was probably related to the activation of the macrophage function revealed by the
observed increases in phagocytosis and intracellular killing of peritoneal macrophages induced by Ashwagandha
treatment in mice [30]. Antibiotic activity of Withaferin A is due to the presence of the unsaturated lactone-ring. The
lactone showed strong therapeutic activity in experimentally induced abscesses in rabbits, the being somewhat
stronger than that of Penicillin. It substantiates the reputation of the leaves as a cure for ulcers and carbuncles in the
indigenous system of medicine [31].
Antioxidant effect
The brain and nervous system are relatively more susceptible to free radical damage than other tissues
because they are rich in lipids and iron, both known to be important in generating reactive oxygen species. Free radical
damage of nervous tissue may be involved in normal aging and neurodegenerative diseases, e.g., epilepsy,
schizophrenia, Parkinson’s, Alzheimer’s, and other diseases. The active principles of WS, sitoindosides VII-X and
withaferin A (glycowithanolides), have been tested for antioxidant activity using the major free-radical scavenging
enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) levels in the rat brain frontal
cortex and striatum. Decreased activity of these enzymes leads to accumulation of toxic oxidative free radicals and
resulting degenerative effects. An increase in these enzymes would represent increased antioxidant activity and a
protective effect on neuronal tissue. Active glycowithanolides of WS were given once daily for 21 days, dose-related
increased in all enzymes were observed; the increases comparable to those seen with deprenyl (a known antioxidant)
administration. This implies that WS does have an antioxidant effect in the brain, which may be responsible for its
diverse pharmacological properties [32]. In another study, an aqueous suspension of WS root extract was evaluated for
its effect on stress-induced lipid peroxidation (LPO) in mice and rabbits. LPO blood levels were increased by
lipopolysaccharides (LPS) from Klebsiella pneumoniae and peptidoglycans (PGN) from Staphylococcus aureus.
Simultaneous oral administration of WS extract prevented an increase in LPO [33]. Apart from hepatic lipid peroxidation
(LPO), the serum enzymes, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, were
assessed as indices of hepatotoxicity. Silymarin (20 mg/kg, p.o.) was used for comparison. Iron overload induced
marked increase in hepatic LPO and serum levels of the enzymes, which was attenuated by glycowithanolides (WSG) in
a dose-related manner, and by silymarin [34].
Anti-aging activity
Ashwagandha was tested for its anti-aging properties in a double-blind clinical trial. A group of 101 healthy
males, 50-59 years old were given the herb at a dosage of 3 grams daily for one year. The subjects experienced
significant improvement in hemoglobin, red blood cell count, hair melanin, and seated stature. Serum cholesterol
decreased and nail calcium was preserved.Seventy percent of the research subjects reported improvement in sexual
performance [35].
Anticonvulsant Activity
Administration of Asgand root extract was found to reduce jerks and clonus in 70% and 10% animals
respectively with dose of 100mg/kg and reduction in the severity of pentylene tetrazole (PTZ)-induced convulsions was
evident from EEG wave pattern [36]. Asgand root extract showed reduction in severity of motor seizures induced by
electrical stimulation in right basilateral amygdaloid nuclear complex through bipolar electrodes. The protective effect
of Asgand extract in convulsions has been reported to involve GABAergic mediation [37].
Nootropic effect
Effects of sitoindosides VII-X and withaferin isolated from aqueous methanol extract of roots of cultivated
varieties of WS were studied on brain cholinergic, glutamatergic and GABAergic receptors in rats. The compounds
slightly enhanced acetylcholinesterase (AChE) activity in the lateral septum and globus pallidus, and decreased AChE
activity in the vertical diagonal band. These changes were accompanied by enhanced M1-muscarinic-cholinergic
receptor binding in lateral and medial septum as well as in frontal cortices, whereas the M2- muscarinic receptor-
binding sites were increased in a number of cortical regions including cingulate, frontal, parietal, and retrospinal cortex.
The data suggest the compounds preferentially affect events in the cortical and basal forebrain cholinergic-signal
transduction cascade. The drug-induced increase in cortical muscarinic acetylcholine receptor capacity might partly
explain the cognitionenhancing and memory-improving effects of WS extracts in animals and in humans [38]. In a study
by Zhao et al [39] Withanoside IV (a constituent of WS; the root of WS) induced neurite outgrowth in cultured rat cortical
neurons. Oral administration of withanoside IV significantly improved
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memory deficits in Abeta-injected mice and prevented loss of axons, dendrites, and synapses. Sominone, an aglycone
of withanoside IV, was identified as the main metabolite after oral administration of withanoside IV. Sominone induced
axonal and dendritic regeneration and synaptic reconstruction significantly in cultured rat cortical neurons damaged by
Abeta. Withanoside IV may ameliorate neuronal dysfunction in Alzheimer's disease and that the active principle after
metabolism is sominone. In another study reserpine treated animals also showed poor retention of memory in the
elevated plus maze task paradigm. Chronic WS administration significantly reversed reserpine-induced retention
deficits [40]. In different study with WS root extract improved retention of a passive avoidance task in a step-down
paradigm in mice. WS also reversed the scopolamine-induced disruption of acquisition and retention and attenuated
the amnesia produced by acute treatment with electroconvulsive shock (ECS), immediately after training. Chronic
treatment with ECS, for 6 successive days at 24 h intervals, disrupted memory consolidation on day 7. Daily
administration of WS for 6 days significantly improved memory consolidation in mice receiving chronic ECS treatment.
WS, administered on day 7, also attenuated the disruption of memory consolidation produced by chronic treatment with
ECS. On the elevated plus-maze, WS reversed the scopolamine-induced delay in transfer latency on day 1. On the basis
of these findings, it is suggested that WS exhibits a nootropic-like effect in naïve and amnesic mice [41].
Antiparkinsonian properties
Parkinson's disease is a neurodegenerative disease characterized by the selective loss of dopamine (DA)
neurons of the substantia nigra pars compacta. The events, which trigger and/or mediate the loss of nigral DA neurons,
however, remain unclear. Neuroleptic-induced catalepsy has long been used as an animal model for screening drugs
for Parkinsonism. Administration of haloperidol or reserpine significantly induced catalepsy in mice. WS significantly
inhibited haloperidol or reserpine-induced catalepsy and provide hope for treatment of Parkinson's disease [42]. In
another study, 6-Hydroxydopamine (6-OHDA) is one of the most widely used rat models for Parkinson's disease. There is
ample evidence in the literature that 6-OHDA elicits its toxic manifestations through oxidant stress. Antiparkinsonian
effects of WS extract has been reported due to potent antioxidant, antiperoxidative and free radical quenching
properties in various diseased conditions. Rats were pretreated with the WS extract orally for 3 weeks. On day 21, 6-
OHDA was infused into the right striatum while sham operated group received the vehicle. Three weeks after 6-OHDA
injections, rats were tested for neurobehavioral activity and were killed 5 weeks after lesioning for the estimation of
lipidperoxidation, reduced glutathione content, activities of glutathione-S-transferase, glutathione reductase, GPX, SOD
and CAT, catecholamine content, dopaminergic D2 receptor binding and tyrosine hydroxylase expression. WS extract
reversed all the parameters significantly in a dose-dependent manner [43]. Tardive dyskinesia is one of the major side
effects of long-term neuroleptic treatment. The pathophysiology of this disabling and commonly irreversible movement
disorder is still obscure. Vacuous chewing movements in rats are widely accepted as an animal model of tardive
dyskinesia. Oxidative stress and products of lipid peroxidation are implicated in the pathophysiology of tardive
dyskinesia. Repeated treatment with reserpine on alternate days for a period of 5 days significantly induced vacuous
chewing movements and tongue protrusions in rats. Chronic treatment with WS root extract for a period of 4 weeks to
reserpine treated animals significantly and dose dependently reduced the reserpineinduced vacuous chewing
movements and tongue protrusions. Oxidative stress might play an important role in the pathophysiology of reserpine-
induced abnormal oral movements [44]. In another study, WS glycowithanolides (WSG) administered concomitantly with
haloperidol for 28 days, inhibited the induction of the neuroleptic TD. Haloperidol-induced TD was also attenuated by
the antioxidant, vitamin E, but remained unaffected by the GABAmimetic antiepileptic agent, sodium valproate, both
agents being administered for 28 days like WSG. Antioxidant effect of WSG, rather than its GABA-mimetic action
reported for the prevention of haloperidol-induced TD [45]. WS significantly reversed the catalepsy, tardive dyskinesia
and 6- Hydroxydopamine elicited toxic manifestations and may offer a new therapeutic approach to the treatment of
Parkinson's disease.
Cardiovascular protection
WS 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 [46]. 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.
WS showed strong cardioprotective effect in the experimental model of isoprenaline-induced myonecrosis in rats.
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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 [47].
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 [48]. 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 [44].
Administration of Asgand extract was found to significantly reduce leucopenia induced by sub-lethal dose of gamma
radiation [49]. 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 [50].
Anti-hyperglycaemic Effect
Asgand along with other ingredients of a composite formulation (Transina) have been reported to decrease
streptozocin (STZ)-induced hyperglycaemia in rats. This anti-hyperglycaemic effect may be due to pancreatic islet free
radical scavenging activity because the hyperglycaemic activity of STZ is a consequence of decrease in pancreatic islet
cell superoxide dismutase (SOD) activity leading to the accumulation of degenerative oxidative free radicals in islet -beta
cells [51].
Hypolipidemic effect
WS root powder decreased total lipids, cholesterol and triglycerides in hypercholesteremic animals. On the
other hand, significantly increased plasma HDL-cholesterol levels, HMG-CoA reductase activity and bile acid content of
liver. A similar trend also reported in bile acid, cholesterol and neutral sterol excretion in the hypercholesteremic
animals with WS administration. Further, a significant decrease in lipid-peroxidation occurred in WS administered
hypercholesteremic animals when compared to their normal counterparts. However, WS root powder was also effective
in normal subjects for decreasing lipid profiles [52]. In another study with aqueous extract of fruits of Withania coagulans
to high fat diet induced hyperlipidemic rats for 7 weeks, significantly reduced elevated serum cholesterol, triglycerides
and lipoprotein levels. This drug also showed hypolipidemic activity in triton-induced hypercholesterolemia. The
histopathological examination of liver tissues of treated hyperlipidemic rats showed comparatively lesser degenerative
changes compared with hyperlipidemic controls. The hypolipidemic effect of Withania coagulans fruits reported to be
comparable to that of an Ayurvedic product containing Commiphora mukkul [53]. In another study, hypoglycemic,
diuretic and hypocholesterolemic effects of roots of WS 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 [54].
Sexual behavior
Methanolic root extract of WS were orally administered at dose 3000 mg/kg/day of 7 days in rats. Their sexual
behaviour was evaluated 7 days prior to treatment, day 3 and 7 of treatment, and day 7, 14 and 30 post-treatment by
pairing each male with a receptive female. The WS root extract induced a marked impairment in libido, sexual
performance, sexual vigour, and penile erectile dysfunction. These effects were partly reversible on cessation of
treatment. This antimasculine effect was not due to changes in testosterone levels but attributed to
hyperprolactinemic, GABAergic, serotonergic or sedative activities of the extract. WS roots may be detrimental to male
sexual competence [55].
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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 [56]. One of the most exciting of the possible uses of
Ashwagandha is its capacity to fight cancers by reducing tumor size [57, 58]. To investigate its use in treating various
forms of cancer, the antitumor effects of Withania somnifera have been studied by researchers. In one study, the herb
wasn evaluated for its anti-tumor effect in urethane-induced lung tumors in adult male mice[59]. 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.
Other Therapeutic Benefits
Further studies have also shown ashwagandha to be effective in the treatment of osteoarthritis, [60]
inflammation [61], stroke [62], and tardive dyskinesia [63]. Ashwagandha has been shown to be a potential antimicrobial
agent, with antifungal activity [64], and moderate antibacterial activity against Staphyloccus aureus and Pseudomonas
Aeruginosa bacteria strains [65].
CONCLUSION
Withania somnifera (Ashwagandha) is a plant used in medicine from the time of Ayurveda, the ancient system
of Indian medicine. The plant has also been widely studied for their various pharmacological activities like antioxidant,
anxiolytic, adaptogen, memory enhancing, antiparkinsonian, antiinflammatory, antitumor properties. Various other
effects like immunomodulation, hypolipidemic, antibacterial, cardiovascular protection, sexual behaviour, have also
been studied. Although the results from this review are quite promising for the use of WS as a multi-purpose medicinal
agent, several limitations currently exist in the current literature. While WS has been used successfully in Ayurvedic
medicine for centuries, more clinical trials should be conducted to support its therapeutic use.
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... [7,8] Withania somnifera also commonly known as Ashwagandha, winter cherry and Indian (like as children, young, elders) as well as both sex (male and female) even it is also useful in the pregnancy time without any type of adverse effect. [9] The Withania somnifera plant has different more important species of genus such as withania adunensis, withania simonii, withania riebeckii are commonly known species which are easily cultivated in diffirent countries of the world and have their therapeutic potential. There are also found to be two sub-species of the Withania somnifera plant as Withania somnifera dunnal and withnania somnifera kaul. ...
... It can be cultivated in different countries such as India, China, Africa, Pakistan, Afghanistan etc. in India it is cultivated in some drier or sub-tropical states namely as Rajasthan, Punjab, Uttar Pradesh, Gujarat, Madhya Pradesh are main known for the major production of Ashwagandha. [9] The roots of this plant have shape long tuberous (10-17.5 cm long and 6-12 cm in diameter), cylindrical, straight, fleshy, unbranched, whitish brown aromatic in nature which are mainly used therapeutically. The leaves are simple, alternate, sub-opposition; smaller up to 10 cm long the floral region. ...
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Withania somnifera also commonly known as Ashwagandha, winter cherry and Indian ginseng, is a most important traditional plant. Withania somnifera plant belongs to the family Solanaceae. The roots of Ashwagandha plant has been consist two major active constituents are steroidal alkaloide and steroidal lactone which is a class of withanolides. In this research work study, the pharmacological screening of anxiolytic activity of alcoholic extract of withania somnifera roots in albino rats was compared with the control (vehicle) and standard group (diazepam 4 mg/kg, i.p. a chemical drug). The alcoholic extract of withania somnifera roots was administered orally in to two test groups A and B such as: 150 mg/kg and 250 mg/kg suspended in vehicle. The behavioral test was measured by using two anxiolytic models as elevated plus maze (EPM) and head dip chamber. The result shows increase the open arms entries and time spent in open arms in EPM, in head dip chamber model decreases the head dipping and rearing.
... However, the plant still exhibits high anti-inflammatory activity associated with steroid content, withaferin A, the main component of those steroids (Jana and Charan, 2018). The anti-inflammatory activity is similar to glucocorticoid hydrocortisone (Narinderpal et al., 2013). ...
... According to Narinderpal et al. (2013), the arthritic syndrome was suppressed by withaferin A, and hydrocortisone-treated animals lost weight, whereas withaferin A-treated animals gained weight. ...
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Poultry production significantly contributes to bridging the food gap worldwide. Several nations have limited the usage of antibiotic growth promotors due to bacterial resistance to antibiotics and the occurrence of residual antibiotics in the edible tissues of birds. The world is now turning to using natural alternatives to increase poultry production as well as birds’ resistance to diseases. Withania somnifera (WS; family: Solanaceae) is a precious medicinal herb utilized in several countries due to its distinct chemical, medicinal, and physiological properties. This plant has antioxidant, anti-aging, antimicrobial, antitumor, hepatoprotective, cardioprotective, neuroprotective, immunomodulatory, antidiabetic, antistress, and growth-promoting activities. In poultry, the dietary inclusion of WS revealed a promising result in enhancing productive performance, increasing disease resistance, reducing stress effects, and maintaining the bird’s health. Thus, the current review highlights the morphological features, distribution, chemical structure, and pharmacological features of Withania somnifera as a growth promoter herb for farming broiler chickens.
... In silico toxicity evaluation of novel compounds isolated from Withania somnifera reflects the growing interest in the therapeutic potential of this medicinal plant. W. somnifera, or ashwagandha, is celebrated for its diverse pharmacological activities, attributed to its bioactive compounds, including alkaloids and withanolides (Narinderpal et al., 2013;Gujjeti et al., 2013). Recent research has highlighted these compounds' roles in mitigating stress, enhancing cognitive function, and exhibiting anti-inflammatory and anticancer properties (Burgula et al., 2024;Swapna et al., 2024). ...
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This study validates and expands upon previous findings regarding two novel compounds isolated from Withania somnifera, emphasizing their potential therapeutic applications. The significance of this work lies in its comprehensive in silico toxicity analysis, which assesses the safety and efficacy of these compounds. Using ACD/ChemSketch and OpenBabel software, the chemical structures of the compounds were prepared and converted into SMILES format for further analysis. The PASS prediction software indicated that Compound 1 exhibits significant biological activities, including strong potential as a growth hormone agonist and antineoplastic agent, while Compound 2 also shows promising activity as an antineoplastic and CYP3A substrate. Drug-likeness assessments using SwissADME revealed that both compounds conform to multiple drug-likeness rules, with Compound 1 demonstrating slightly better properties than Compound 2. Furthermore, ADMET analysis indicated favorable pharmacokinetic profiles for both compounds, with distinct advantages in absorption and distribution characteristics. These findings suggest that both compounds possess significant therapeutic potential, warranting further investigation for their development as drug candidates.
... The commercially available dental products due to its proven beneficial effects have been in avid and routine utilization in various dental treatments as it has been studied for its enormous dental and medicinal effects even though with persistent side effects ranging from oral ulcers, mucosal irritation, discoloration, staining and unpleasant taste. [4,5] The researchers have been under constant quest to substitute these pre existing products with more reliable, easily available and financially pliable naturally occurring derivatives with minimal adverse reactions. [6] This led to the incorporation of sparcely utilized herbs and ayurvedic combinations into formulation of the adviseable alternatives for the existent dental products. ...
... Withania somnifera, also known as ashwagandha, Indian ginseng, and winter cherry, has been an important herb in the Ayurvedic and indigenous medical systems for over 3000 years [1] . It is a perennial shrub from the Solanaceae or Nightshade family [2] The roots of the plant are categorized as immune boosters, which are reputed to promote health and longevity by augmenting defense against disease, arresting the aging 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 [3] . ...
... Being rasayana, this plant has the potential to prepare the human body to efficiently defend against disease. Calming the mind, relieving weakness and nervous fatigue, and promoting sexual vitality and healthy sleep are some of the most important benefits of this high-value medicinal plant (Narinderpal et al. 2013). Being a part of more than hundreds of ayurvedic formulations, this plant remains in high demand. ...
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Ashwagandha (Withania somnifera Dunal. Linn.) also known as Indian ginseng is the most widely used herb to boost the immune system. The main economic part of this plant is its roots and the principal active ingredients in roots are a group of steroidal lactones; collectively known as withanolides. Achlorophyllous holoparasitic angiosperm nodding broomrape (Orobanche cernua Loefl.) is a root parasite living on a range of host plant species. To our best knowledge, there have been no reports on the effects of nodding broomrape parasitism on the growth, behaviour, and quality of W. somnifera plants. Physiological and biochemical parameters of broomrape-infected plants were studied and compared with those of uninfected plants. At 120 days after sowing (DAS) the net photosynthetic rate (PN) and stomatal conductance (gS) in infected plants were 68% and 69%, respectively of those of the uninfected plants. The leaf nitrate reductase activity in infected plants was 88% and 48% of uninfected plants at 100 and 120 DAS, respectively. Chemo-profiles showing the absence of withanolide in broomrape stems demonstrated that this parasite does not mine withanolide from the host plant. Broomrape infestation had resulted in overall stunted growth causing an 83% decline in leaf area, reduced total biomass by 82%, decreased root yield by 68%, and major withanolide yield by 38% at 145 days after sowing. Future research on the management of broomrape in W. somnifera is suggested to prevent a huge yield loss in this important medicinal root crop.
Chapter
Plants produce a variety of phytochemicals in response to the different biotic or abiotic stress conditions. These metabolites not provide protection to the plant and help in its survival. But are also exploited by humans for their own needs. Secondary metabolites of Ashwagandha have great therapeutic importance. The plants herbal rejuvenative properties have made plant exceptionally esteemed in pharmacology and naturopathy. The active biochemical constituents of W. somnifera are steroidal lactones, flavonoids, alkaloids, sitoindosides, glycowithaolides, withanosides, amino acids, saponins etc., all help in plant defense. Withanolides also act in plant defense mechanism actively protecting the plant from pathogens and in withstanding biotic and a biotic stress conditions. Sterols released by WS also having protective functioning in plants and improve the phenotypic and metabolic activities in plants under stress conditions. The plants response to these stress conditions by generation of stress-tolerating enzymes such as superoxide dismutase and glutathione reductase. Increase in production of secondary metabolite Withaferin (terpenoids) protects plants from cold stress via production of antioxidant enzymes. Terpenoids act as signaling molecules in plants and help in defense response toward stress conditions (biotic/abiotic stress). The phytochemical constituent of the plant contributes in drugs as well as assists with getting the physiological property for the treatment of various illnesses. Because of its significance in herbal drugs, many types of exploration are proceeding to determine new substance compounds and furthermore distinguishing the degree of toxicity.
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Objectives Stress is an aversive stimulus which disrupts the biological milieu of the organism and a variety of emotional and environmental stressors are known to influence allergic and immunological disorders like bronchial asthma but the pharmacological basis of such interactions is not clearly defined. Withania somnifera (ashwagandha) is a potent anti-stress agent used widely in Indian traditional medicine and the present experimental study evaluated the effects of W. somnifera extract (WSE) on chronic stress-induced neurobehavioral and immunological responses in an experimental model of allergic asthma in rats. Methods Wistar rats (200–250 g) were immunized and challenged with ovalbumin (OVA) and exposed to restraint stress (RS) and WSE treatments for 15 days. Following this, anxiety behavior was assessed by the elevated plus maze (EPM) test, and blood and BAL fluid samples were collected for measuring of inflammatory/immune markers by ELISA and biochemical assay. The data of the various treatment groups were analyzed by ANOVA and Tukey’s test. Results Restraint stress (RS) induced anxiogenic behavior in the (EPM) test in OVA immunized rats, and this was attenuated by WSE (200 and 400 mg/kg), in a dose related manner. Examination of blood and BAL fluid in these RS exposed rats also resulted in elevations in IgE, TNF-α and IL-4 levels, which were also attenuated by WSE pretreatments. Further, WSE pretreatment neutralized the such RS induced changes in oxidative stress markers viz. elevated MDA and reduced GSH levels. Conclusions The data pharmacologically validates role of stress in asthma and suggests that adaptogens like WSE could be a potential complementary agent for reducing anxiety as well as airway inflammation by a multi-targeted and holistic approach. The study also highlights the significance of integration of traditional and modern medical concepts in such chronic disorders.
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The Solanaceae family is known as "the night shade family" since it is descended from the genes solanum. There are 98 genera and 2700 species. The plants are found in South and Central America. Leaves are alternating, spiral, and exstipulate. The flowers are bisexual, actinomorphic, and zygomorphic only infrequently. Cork cambium is found in plants of Solanaceae family. The shape, type, texture, and color of the fruit is vary. The majority of seeds in are endospermic. The chemical elements of the Solanaceae family include tropane alkaloids, scopolamine, atropine, hyoscyamine, and nicotine. Members of the Solanaceae family have medicinal and decorative properties. Poisoning and psychotropicactivity is the most common symptoms.
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Nine new steroidal lactones of the withanolide series (withanolides E-M) have been isolated from the leaves of Withania somnifera Dun (Solanaceae) growing in the southern coastal plane of Israel. This population of W. somnifera constitutes a new chemotype and is designated as chemotype III. The following structures have been assigned to seven of the above compounds:Withanolide G, 20α-hydroxy-1-oxo-20R,22R-witha-2,5,8(14),24-tetraenolide (1); withanolide H, 20α,27-dihydroxy-1-oxo-20R,22R-witha-2,5,8(14),24-tetraenolide (2); withanolide I, 20α-hydroxy-1-oxo-20R,22R-witha-3,5,8(14),24-tetraenolide (3); withanolide J, 17α,20α-dihydroxy-1-oxo-20S,22R-witha-2,5,8(14),24-tetraenolide (4); withanolide K, 17α,20α-dihydroxy-1-oxo-20S,22R-witha-3,5,8(14),24-tetraenolide (5); withanolide L, 17α,20α-dihydroxy-1-oxo-20S,22R-witha-2,5,14,24-tetraenolide (6); withanolide M, 17α,20α-dihydroxy-1-oxo-14α,15α-epoxy-20S,22R-witha-2,5,24-trienolide (7).
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The term adaptogen has not yet been accepted in medicine. This is probably due to the difficulties in discriminating adaptogenic drugs from immunostimulators, anabolic drugs, nootropic drugs, and tonics. There can be not doubt, however, that, at least in animal experiments, there are plant drugs capable of modulating distinct phases of the adaptation syndrome as defined by Seyle. These drugs either reduce stress reactions in the alarm phase or retard / prevent the exhaustion phase and thus provide a certain degree of protection against long-term stress. The small number of drugs the antistress activity of which has been proven or reported includes, among others, the plant drugs Ginseng, Eleutherococcus, Withania, Ocimum, Rhodiola, and Codonopsis. This review summarizes the major findings of pharmacological tests and human studies carried out with these drugs. Currently used assay systems allowing detection of antistress activities are also reported. At present the most likely candidates responsible for the putative antistress activity of plant drugs are special steroids, phenylprogane compounds and lignanes, respectively. Apart from influencing activities of the pituitary-adrenal axis and inducing stress proteins, many adaptogens also possess immunomodulatory and / or anabolic activities.
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Abstract Withania somnifera Dun. herbal drug widely used in Indian medicinal systems, was examined for its effect on alpha-2-macroglobulin. Administration of W. somnifera to inflamed rats caused a significant reduction in the level of serum alpha-2-macroglobulin. Unlike non-steroidal anti-in-flammatory drugs, W. somnifera treatment resulted in a specific decrease in the synthesis of alpha-2-macroglobulin and enhancement in the synthesis of total serum proteins suggesting the basis for its wide spectrum of pharmacological activities in diseases involving alterations of serum proteins.