Withania somnifera (WS) is popularly known as Ashwagandha or Winter Cherry (Andallu and Radhika, 2000). It is a green shrub (family Solanaceae) (Dafni and Yaniv, 1994) found throughout the drier parts of India, Baluchistan, Pakistan, Afghanistan, Sri Lanka, Congo, South Africa, Egypt, Morocco and Jordan. In India, it is widely grown in the provinces of Madhya Pradesh, Uttar Pradesh, plains of Punjab and northwestern parts of India like Gujarat and Rajasthan (Bhatia et al., 1987). The plant is popularly known in India by different vernacular names like Punir (Hindi), Ashvaganda (Bengal, Bombay), Aksan (Punjab), Amukkira (Tamil), Tilli (Marathi)
In Ayurveda, W. somnifera is widely claimed to have aphrodisiac, sedative, rejuvenative and life prolonging properties. It is also used as a general energy-enhancing tonic known as Medharasayana (promotes learning and memory) and in geriatric problems (Nadkarni, 1976). The plant has traditionally been used to promote youthful vigor, endurance, strength, health, nurturing the time elements of the body and increasing the production of vital fluids, muscle fat, blood, lymph, semen and cells (Williamson, 2002).
The fruits are reported to be sedative, emetic and stomachic, blood-purifier and febrifuge, as an alternative, diuretic and bitter tonic in dyspepsia as well as a growth promoter in infants. The roots are also used in constipation, senile debility, rheumatism, general debility, nervous exhaustion, loss of memory, loss of muscular energy and spermatorrhoea (Watt, 1972; Singh and Kumar, 1998).
Besides its use as general tonic (Agarwal et al., 1999; Dhuley, 2000), several recent reports have demonstrated immunomodulator and antitumor effects of ashwagandha as well (Sharad et al., 1996; Budhiraja and Sudhir, 1987; Ziauddin et al.,, 1996; Agarwal et al.,, 1999; Devi, 1999; Mirjalili, 2009). Moreover, extracts of various parts of the plant have been reported to possess antioxidant, antiserotogenic, anticancer and anabolic properties and has beneficial effects in the treatment of arthritis, stress and geriatric problems (Asthana and Raina, 1989; Gandhi et al., 1994; Davis and Kuttan, 2000; Singh et al., 2001; Prakash et al., 2001; Mishra et al., 2000; Mirjalali et al., 2009). The plant extracts are also used in folk, ayuvedic, Unini and Sidha systems of medicine. The plant was found to be active against a number of pathogenic bacteria (Kurup, 1956) and possess a strong antibacterial and antifungal activity against various pathogens including Salmonella typhimurium and in the treatment of murine aspergillosis (Dhuley, 1998; Ziauddin et al., 1996; Owais et al., 2005).
The pharmacological activity of roots is attributed to the presence of several alkaloids. The total alkaloidal content of the Indian roots has been reported to vary between 0.13 and 0.31%. In all, 13 dragendorff positive components have been obtained chromatographically. They include cuscohygrine, anahygrine, tropine, pseudotropine and anaferine. There is another alkaloid called withsomine which is repoted from the root of the plant grown in West Germany In addition to alkaloids the root are reported to contain starch, resin, fat, potassium nitrate, phytosterol, reducing sugars, hentriacontane glycosides, dulcitol, withaniol, stearic, palmatic, linoleic, withanic acid, ipuranol and somnirol. Dr. Trebut in 1886 separated an alkaloid from the Mediterranean plant, which forms a crystalline sulphate having hypnotic action, but not producing mydriasis. He provisionally named the alkaloid somniferine.
The hypnotic and sedative properties are due to the presence of an alkaloid “somniferin.” The root contains several alkaloid including withanine, withananine, psedo-withanine, somnine, somniferine. Withferin A has antitumor, antiarthritic, and antibacterial and anti-inflammatory activity. 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
W. somnifera is considered to be a safe drug. In one of the studies, a 2% suspension of ashwagandholine (total alkaloids from the roots of W. somnifera) prepared in ten-percent glycol using two percent gum acacia as suspending agent was used to determine acute toxicity. The acute LD50 value was found to be 465 mg/kg (332–651 mg/kg) in rats and 432 mg/kg (229– 626 mg/kg) in mice (Malhotra et al., 1965). The extract had no profound effect on central nervous system or autonomic nervous system in doses of up to 250 mg/100 g of mice in toxicity studies.
However, it affected spontaneous motor activity in still higher doses. In another long-term study, W. somnifera was boiled in water and administered to rats in their daily drinking water for eight months while monitoring body weight, general toxicity, wellbeing, number of pregnancies, litter size, and progeny weight (Sharma et al., 1986). The estimated dose received by the animal was 100 mg/kg/day.
The liver, spleen, lungs, kidneys, thymus, adrenals, and stomach were examined histopathologically and were all found to be normal. The rats treated with W. somnifera showed weight gain as compared to the control group. The offsprings of the group receiving W. somnifera were found to be healthier compared to control group (Sharma et al., 1986). The different doses of the extract (30, 75 and 150 mg/kg) potentiated pentobarbitoneinduced sleeping time in a dose-dependent fashion (Prabhuet al., 1990).
Several studies demonstrated that Ashwagandha reduces blood sugar levels. A test tube study found that it increased insulin secretion and improved peripheral tissue sensitivity to insulin. One study revealed that people with schizophrenia, those treated with Withania somnifera for 4 weeks had an average reduction in fasting blood sugar levels of 13.5 mg/dl, compared to a 4.5 mg/dl reduction in those who received a placebo17. Transina, one ayurvedic formulation which contain Ashwagandha as active ingredient have been reported to decrease streptozotocin (STZ)-induced hyperglycaemia in rats. This hypoglycaemic effect may be attributed 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
Aqueous root extract of Asgand was found to possess strong antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA) as revealed by the in vitro agar well diffusion assay. The separation of the bioactive compounds from the plant extract was carried out using two dimensional thin layer chromatography (TLC) and contact bioautography. The antioxidant activity was estimated to be Trolox Equivalent Antioxidant Capacity of 9.83mg/gm of dry weight of extract and reducing power was 0.11mg/gm of dry weight of extract using ascorbic acid as standard. Our study suggests that the bioactive fractions separated from aqueous extract of Withania somnifera are a potential source of antibacterial compounds with antioxidant property
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 (Khare, 2007). 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 (Anonymous, 1982, Rastogi et al., 1998). 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 (Sharma et al., 1991, Sahni et al., 1994).
In a double-blind clinical trial, ashwagandha 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 hemoglobin, red blood cell count, hair melanin, and seated stature was observed. Serum cholesterol decreased and nail calcium was preserved. Erythrocyte sedimentation rate decreased significantly and 71.4 percent reported improvement in sexual performance
Chronic stress (CS) can result in a number of adverse physiologic conditions including cognitive deficit, immunosuppression, sexual dysfunction, gastric ulceration, irregularities in glucose homeostasis, and changes in plasma corticosterone levels. In a rat model of chronic stress Withania somnifera and Panax ginseng extracts were compared for their ability to attenuate some effects of chronic stress. Both botanicals were able to decrease the number and severity of CS-induced ulcers, reverse CS-induced inhibition of male sexual behavior, and inhibit the adverse effects of CS on retention of learned tasks.
Both botanicals also reversed CS-induced immunosuppression, but only the Withania extract increased peritoneal macrophage activity in the rats. The activity of the Withania extract was approximately equal to the activity of the Panax 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
Withaferin A and withanolide D are reported to be significant anti-tumor and radio-sensitizing withanolides (Devi et al., 1992, 1993, 1996; Lyon and Kuttan, 2004). 1-oxo-5ß, 6β-epoxy-witha-2-enolide is another constituent of W. somnifera reported to reduce the skin carcinoma induced by UV radiations (Mathur et al., 2004). Withaferin A acts as a mitotic poison arresting the division of the cultured human larynx carcinoma cells at metaphase. It also produced a significant dose dependent retardation of the growth of Ehrlich ascites carcinoma, sarcoma 180, and sarcoma Black and E 0771 mammary adenocarcinoma (Davis and Kuttan, 1998).
Methanolic extract of W. somnifera has been used in stem cell proliferation (Kuttan, 1996). It also inhibited growth of breast, lung, central nervous system and colon cancer cell lines by decreasing their viability in doze dependent manner and therefore holds promise as a chemotherapeutic agent (Jayaprakasan et al., 2003). The withaferin A-mediated suppression of breast cancer cell viability correlated with apoptosis induction characterized by DNA condensation, cytoplasmic histone–associated DNA fragmentation, and cleavage of poly-(ADP-ribose)-polymerase (Silvia et al., 2008). Chemo-preventive activity is attributed partly to the antioxidant/free radical scavenging activity of the extract (Prakash et al., 2002).
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 promote the generation of reactive oxygen species (Halliwell & Gutteridge, 1989). Free radical damage of nervous tissue may be responsible for neural loss in cerebral ischemia and may be involved in aging and neurodegenerative diseases, e.g., epilepsy, schizophrenia, Parkinson’s, Alzheimer’s and other diseases (Jesberger and Richardson, 1991, Sehgal et al., 2012).
The active principles of W. somnifera, sitoindosides VII-X and withaferin A (glycowithanolides), are reported to increase levels of endogenous superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and ascorbic acid, with a concomitant decrease in lipid peroxidation (Dhuley, 1998; Bhattacharya, 2001; Jayaprakasam et al., 2004; Bhatnagar, 2005; Mirjalali et al., 2009). A decrease in the activity of these enzymes is known to lead accumulation of oxidative free radicals and resulting in degenerative effects.
Withania somnifera effectively help to improve heart health by reducing cholesterol and triglyceride levels. Animals’ studies have found that it significantly decreases these blood fats. One experimental study in rats found that it lowered total cholesterol by as much as 53% and triglycerides by nearly 45%. In a 60 day experimental study of chronically stressed adults, the group taking the higher dosage of Ashwagandha experienced a 17% decrease in LDL cholesterol and 11% decrease in triglycerides.
Withania somnifera root powder reduced 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.
In another study with hydroalcoholic 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. In one study, six mild non-insulin dependent diabetes mellitus subjects and six mild hypercholesterolemic subjects were treated with the powder of roots of Withania somnifera for 30 days. Various parameters were assessed in the blood and urine samples of the subjects.
Decrease in blood glucose was comparable to that of an oral hypoglycaemic drug. Significant increase in urine sodium, urine volume, significant decrease in serum cholesterol, triglycerides, LDL and VLDL-cholesterol were observed, indicating that root of Withania somnifera is a potential source of hypoglycaemic, diuretic and hypocholesterolemic agents.
The efficacy of Withania somnifera on immunomodulation was tested in experimental azoxymethane induced colon cancer in mice. Azoxymethane 15 mg/kg was injected intraperitoneally once a week for 28 days. The colon cancer was confirmed by the appearance of aberrant crypt foci (ACF) in the colons of the experimental mice. The progression in colon tumor development was correlated with the appearance of the histological biomarker and ACF. Animals were treated with 400 mg/kg body weight of Withania somnifera extract once a week for four weeks orally. After that the animals were sacrificed and analyzed for immunocompetent cells, immune complexes and immunoglobulins. Withania somnifera significantly altered the level of leucocytes, lymphocytes, neutrophils, immune complexes and immunoglobulins (Ig) A, G and M. The azoxymethane induced colon cancer and immune dysfunction was better controlled by Withania somnifera
Total alkaloidal fraction of root extract showed prolonged hypotensive, bradycardiac and respiratory stimulant activities in dogs. Hypotensive effect was mainly due to autonomic ganglionblocking action and was augmented by the depressant action on higher cerebral centres. The total alkaloids produced a taming and a mild depressant effect (tranquillizer-sedative type) on the CNS in several experimental animals (Rastogi et al., 1998). Systemic administration of Asgand root extract led to differential effects on acetylcholinesterase (ACHE) activity in basal forebrain nuclei.
Slightly enhanced ACHE activity was found in the lateral septum and globus pallidus. Asgand root extract affects preferentially 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 cognition-enhancing and memory-improving effects of extract from Withania somnifera observed in animals and humans (Schliebs et al., 1997).
The total alkaloids of Asgand showed relaxant and antispasmodic effects against several spasmogens on intestinal, uterine, bronchial, tracheal and blood vascular muscles. The pattern of smooth muscle activity of the alkaloids was similar to that of papaverine which suggested a direct musculotropic action (Anonymous, 1982).
Hypoglycemic, diuretic, and hypocholesterolemic effects of ashwagandha root were assessed in human subjects, in which six type 2 diabetes mellitus subjects and six mildly hypercholesterolemic subjects were treated with a powder extract for 30 days. A decrease in blood glucose comparable to that of an oral hypoglycemic drug was observed. Significant increases in urine sodium, urine volume, and decreases in serum cholesterol, triglycerides, and low-density lipoproteins were also seen
Animal studies reveal ashwaganda has a thyrotropic effect. An aqueous extract of dried Withania root was given to mice via gastric intubation at a dose of 1.4 g/kg body weight daily for 20 days. Serum was collected at the end of the 20- day period and analyzed for T3 and T4 concentrations and lipid peroxidation was measured in liver homogenate via antioxidant enzyme activity. Significant increases in serum T4 were observed, indicating the plant has a stimulatory effect at the glandular level
No changes in T3 levels were observed. Withania may also stimulate thyroid activity indirectly, via its effect on cellular antioxidant systems. Withania extract significantly decreased lipid peroxidation in the liver homogenate and significantly increased catalase activity, promoting scavenging of free radicals that can cause cellular damage. These results indicate ashwaganda may be a useful botanical in treating hypothyroidism
Ashwagandha powder has been found useful in acute rheumatoid arthritis and reduces the discomfort associated with arthritis (Bector et al., 1968). This property has been attributed to the active principle withaferin A.
Increase fertility in men
Ashwagandha helps increase testosterone levels and significantly boosts sperm quality and fertility in men. In a study of 75 infertile men, the group treated with Ashwagandha had an increase in sperm count and motility.