€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ BIOCHEMICAL MEDICINE AND METABOLIC BIOLOGY***** Begum VH Sadique J Effect of Withania somnifera on glycosaminoglycan synthesis in carrageenin-induced air pouch granuloma. In: Biochem Med Metab Biol (1987 Dec) 38(3):272-7 The effect of W. somnifera on glycosaminoglycan synthesis in the granulation tissue of carrageenin-induced air pouch granuloma was studied. W. somnifera was shown to exert significant inhibitory effect on incorporation of 35S into the granulation tissue. The uncoupling effect on oxidative phosphorylation (ADP/O ratio reduction) was also observed in the mitochondria of granulation tissue. Further, Mg2+ dependent ATPase activity was found to be influenced by W. somnifera. W. somnifera also reduced the succinate dehydrogenase enzyme activity in the mitochondria of granulation tissue. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****EXPERIENTIA***** Chakraborti SK De BK Bandyopadhyay T Variations in the Antitumor Constituents OF WITHANIA SOMNIFERA In: Experientia (1974) 30(8):852-853 4beta, 20alpha-dihydroxy-1-oxo- 5beta,6beta-epoxy-witha-2,24-dienolide was purified from the leaves of Withania somnifera from West Bengal and identified as the active antitumor principle, as compared to Withaferin A from the same species occurring in Tamil Nadu. In addition to 95% inhibition of murine S-180, it was active against KB cells (LD(50) 1 ug/ml). (6 refs) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****INDIAN JOURNAL OF EXPERIMENTAL BIOLOGY***** Devi PU Sharada AC Solomon FE Kamath MS In vivo growth inhibitory effect of Withania somnifera (Ashwagandha) on a transplantable mouse tumor, Sarcoma 180. In: Indian J Exp Biol (1992 Mar) 30(3):169-72 Withania somnifera is a medicinal plant used in the treatment of a variety of ailments in the Ayurvedic system. Alcoholic extract of the root of the plant was injected(ip) at daily doses of 200 to 1000 mg/kg body wt for 15 days starting from 24 hr after intradermal inoculation of 5 x 10(5) cells of S-180 in BALB/c mice. Solid tumor growth was monitored for 100 days. Doses of 400 mg/kg and above produced complete regression of tumor after an initial growth, the percentage of complete response (CR) increasing with increasing drug dose. A 55% CR was obtained at 1000 mg/kg drug administration, but this dose also produced some mortality among the animals. A significant increase in the volume doubling time and growth delay was seen when the drug dose was increased from 500 to 750 mg/kg body wt, but further increase in drug dose to 1000 mg/kg did not produce any significant increase in these responses. Cumulative doses of 7.5 to 10 g at daily doses of 500 or 750 mg/kg seems to produce a good response in this tumor. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Devi PU Sharada AC Solomon FE Antitumor and radiosensitizing effects of Withania somnifera (Ashwagandha) on a transplantable mouse tumor, Sarcoma-180. In: Indian J Exp Biol (1993 Jul) 31(7):607-11 Antitumor and radiosensitizing effects of alcoholic root extract of W. somnifera and their modification by heat were studied in vivo on Sarcoma-180 grown on the dorsum of adult BALB/c mouse. Ashwagandha (AT) was injected (ip) at a dose of 500 mg/kg body wt for 10 consecutive days into mouse bearing tumor of 50 +/- 5 mm3, with or without a local treatment of 10 Gy gamma radiation (RT) or hyperthermia at 43 degrees C for 30 min (HT) or both on 5th day of AT. The response was assessed on the basis of tumor regression, growth delay, animal survival and changes in the tumor GSH content. Ashwagandha, RT and HT individually produced 18, 38 and 45% complete response (CR) respectively, but RT gave the best long term survival. Ashwagandha increased the effect of radiation on tumor regression as well as growth delay, but AT + HT gave a better tumor cure. However, both these combinations gave almost identical long term survival, which was not much higher than that produced by RT alone. The combination of Ashwagandha for 10 days with one local exposure to RT followed by HT significantly increased the tumor cure, growth delay of partially responding tumors and animal survival. This combination also significantly and synergistically depleted the tumor GSH level, with no recovery even at 3 hr after treatment. It is concluded that Ashwagandha, in addition to having a tumor inhibitory effect, also acts as a radiosensitizer and heat enhances these effects. The severe depletion in the tumor GSH content by the combination treatment must have enhanced the tumor response, as the inherent protection by the thiol will be highly reduced. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****INDIAN JOURNAL OF MEDICAL RESEARCH***** Mehta AK Binkley P Gandhi SS Ticku MK Pharmacological effects of Withania somnifera root extract on GABAA receptor complex. In: Indian J Med Res (1991 Aug) 94:312-5 A methanolic extract of W. somnifera root inhibited the specific binding of [3H]GABA and [35S]TBPS, and enhanced the binding of [3H]flunitrazepam to their putative receptor sites. The extract (5 micrograms) inhibited [3H]GABA binding by 20 +/- 6 per cent whereas a concentration of 1 mg of the extract produced 100 per cent inhibition. The extract (5-100 micrograms) produced 20 +/- 4 to 91 +/- 16 per cent enhancement of [3H]flunitrazepam binding. In functional studies using 36Cl-influx assay in mammalian spinal cord neurons, W. somnifera root extract increased 36Cl-influx in the absence of GABA. This effect on 36Cl-influx was blocked by bicuculline and picrotoxin; and enhanced by diazepam. These results suggest that the W. somnifera extract contains an ingredient which has a GABA-mimetic activity. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****INDIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY***** Budhiraja RD Sudhir S Garg KN Cardiovascular effects of a withanolide from Withania coagulans fruits. In: Indian J Physiol Pharmacol (1983 Apr-Jun) 27(2):129-34 A new withanolide, with a unique chemical structure similar to the aglycones of the cardiac glycosides, with mol. wt. 488 6, m. p. 260- 261 degrees, isolated from the fruits of Withania coagulans, was screened for cardiovascular effects. At doses of 5 mg/kg body weight, the withanolide produced a moderate fall of blood pressure in dogs (34 +/- 2.1, mm Hg) which was blocked by atropine and not by mepyramine or propranolol. In rabbit Langendorff preparation and ECG studies, it produced myocardial depressant effects but in perfused frog heart it produced mild positive inotropic and chronotropic effects. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****INTERNATIONAL JOURNAL OF RADIATION BIOLOGY***** Devi PU Akagi K Ostapenko V Tanaka Y Sugahara T Withaferin A: a new radiosensitizer from the Indian medicinal plant Withania somnifera. In: Int J Radiat Biol (1996 Feb) 69(2):193-7 Withaferin A, a steroidal lactone isolated from the roots of the Indian medicinal plant Withania somnifera, reduced survival of V79 cells in a dose-dependent manner. LD50 for survival was 16 microM. One-hour treatment with a non-toxic dose of 2.1 microM before irradiation significantly enhanced cell killing, giving a sensitizer enhancement ratio (SER) of 1.5 for 37% survival and 1.4 for 10% survival. SER increased with drug dose, but at higher doses the increased lethality appears to be due to two effects-- drug toxicity and radiosensitization. The drug induced a G2/M block, with a maximum accumulation of cells in G2-M phase at 4 h after treatment with 10.5 microM withaferin A in 1 h. The applicability of this drug as a radiosensitizer in cancer therapy needs to be explored. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF ETHNOPHARMACOLOGY***** Grandhi A Mujumdar AM Patwardhan B Comparative pharmacological investigation of Ashwagandha and Ginseng. In: J Ethnopharmacol (1994 Dec) 44(3):131-5 The aqueous suspensions of roots of an Indian drug Ashwagandha and the Korean drug Ginseng were tested comparatively for 2 pharmacological activities, namely the anti-stress activity by the 'mice swimming endurance test' and anabolic activity by noting gain in body weights and levator ani muscle in rats. A significant increase in mice swimming time was shown by Ginseng (P < 0.001) and Ashwagandha (P < 0.01) as compared to the control group. Significant increase in body weights in the Ashwagandha treated group (P < 0.05) was better than Ginseng (P < 0.5). Gain in wet weights of the levator ani muscle were also significant in Ginseng (P < 0.001) and Ashwagandha (P < 0.01) treated groups, however, the weight gain of dried levator ani muscles showed comparable results for both these drugs (P < 0.01). €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ al-Hindawi MK al-Khafaji SH Abdul-Nabi MH Anti-granuloma activity of Iraqi Withania somnifera. In: J Ethnopharmacol (1992 Sep) 37(2):113-6 The granuloma-tissue formation inhibiting activity of various fractions of an extract of the aerial parts of Withania somnifera were established using subcutaneous cotton-pellet implantation in rats. Antiinflammatory activity was retained in the methanolic fractions of the plant extract and was comparable to that of a 5 mg/kg dose of hydrocortisone sodium succinate. Activity was attributed to the high content of biologically active steroids in the plant, of which withaferin A is known to be a major component. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHYTOCHEMISTRY***** Choudhary MI Dur-e-Shahwar Parveen Z Jabbar A Ali I Atta-ur-Rahman Antifungal steroidal lactones from Withania coagulance. In: Phytochemistry (1995 Nov) 40(4):1243-6 Two new withanolides, 14,15 beta-epoxywithanolide I [(20S,22R) 17beta, 20 beta-dihydroxy-14 beta,15 beta-epoxy-1-oxo-witha-3,5,24-trienolide] and 17 beta-hydroxywithanolide K (20S,22R) 14 alpha,17beta,20 beta-trihydroxy-1-oxo-witha-2,5,24-trienolide] have been isolated from the whole plant of Withania coagulance and their structures were elucidated by spectroscopic techniques. The latter compound was found to be active against a number of potentially pathogenic fungi. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ ****REVISTA MEDICO-CHIRURGICALA A SOCIETATII DE MEDICI SI NATURALISTI DIN*** Elsakka M Grigorescu E Stanescu U Stanescu U Dorneanu V New data referring to chemistry of Withania somnifera species. In: Rev Med Chir Soc Med Nat Iasi (1990 Apr-Jun) 94(2):385-7 The withanolides are a category of active principles of great pharmacodynamic importance with regard to our own research. We obtained alkaloids, 18 fatty acids, beta-sitesterol, polyphenols and phytosterols. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Elsakka M Pavelescu M Grigorescu E Withania somnifera, a plant with a great therapeutical future. In: Rev Med Chir Soc Med Nat Iasi (1989 Apr-Jun) 93(2):349-50 Withania somnifera Dun is a plant which drew the interest of many researchers in several countries, either for its active principles or for the extremely important pharmacodynamic or pharmacotherapeutic properties it has and first of all for the content in withanolides, substances with a sterol structure. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€