X-Message-Number: 26323 Date: Sun, 12 Jun 2005 20:09:28 -0700 (PDT) From: Doug Skrecky <> Subject: ashwagandha for dementia, aging? [This appears to deserve a full life span longevity test.] Br J Pharmacol. 2005 Apr;144(7):961-71 Neuritic regeneration and synaptic reconstruction induced by withanolide A. We investigated whether withanolide A (WL-A), isolated from the Indian herbal drug Ashwagandha (root of Withania somnifera), could regenerate neurites and reconstruct synapses in severely damaged neurons. We also investigated the effect of WL-A on memory-deficient mice showing neuronal atrophy and synaptic loss in the brain. Axons, dendrites, presynapses, and postsynapses were visualized by immunostaining for phosphorylated neurofilament-H (NF-H), microtubule-associated protein 2 (MAP2), synaptophysin, and postsynaptic density-95 (PSD-95), respectively. Treatment with A beta(25-35) (10 microM) induced axonal and dendritic atrophy, and pre- and postsynaptic loss in cultured rat cortical neurons. Subsequent treatment with WL-A (1 microM) induced significant regeneration of both axons and dendrites, in addition to the reconstruction of pre- and postsynapses in the neurons. WL-A (10 micromol kg(-1) day(-1), for 13 days, p.o.) recovered A beta(25-35)-induced memory deficit in mice. At that time, the decline of axons, dendrites, and synapses in the cerebral cortex and hippocampus was almost recovered. WL-A is therefore an important candidate for the therapeutic treatment of neurodegenerative diseases, as it is able to reconstruct neuronal networks. Phytother Res. 2001 Sep;15(6):524-8. Nootropic-like effect of ashwagandha (Withania somnifera L.) in mice. Ashwagandha (Withania somnifera L.) root extract (50, 100 and 200 mg/kg; orally) improved retention of a passive avoidance task in a step-down paradigm in mice. Ashwagandha (50, 100 and 200 mg/kg; orally) also reversed the scopolamine (0.3 mg/kg)-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 ashwagandha for 6 days significantly improved memory consolidation in mice receiving chronic ECS treatment. Ashwagandha, administered on day 7, also attenuated the disruption of memory consolidation produced by chronic treatment with ECS. On the elevated plus-maze, ashwagandha reversed the scopolamine (0.3 mg/kg)-induced delay in transfer latency on day 1. On the basis of these findings, it is suggested that ashwagandha exhibits a nootropic-like effect in naive and amnesic mice. Phytomedicine. 2000 Dec;7(6):499-507. Curative property of Withania somnifera Dunal root in the context of carbendazim-induced histopathological changes in the liver and kidney of rat. The liver and kidney of rat underwent severe histopathological lesions when treated with a single bolus dose of carbendazim, a fungicide, particularly affecting the hepatocytes and the renal corpuscles, respectively. The effects appear to be manifestations of the microtubule-disrupting activity of carbendazim. Treatment of carbendazim-treated rats with the powder of tuberous root of Withania somnifera (Ashwagandha) for 48 days resulted in complete cure of these organs. The results indicate that Withania somnifera would be an effective curative for carbendazim-induced histopathological changes in the liver and kidney. Phytomedicine. 2000 Dec;7(6):463-9 Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. The roots of Withania somnifera (WS) are used extensively in Ayurveda, the classical Indian system of medicine, and WS is categorized as a rasayana, which are used to promote physical and mental health, to provide defence against disease and adverse environmental factors and to arrest the aging process. WS has been used to stabilize mood in patients with behavioural disturbances. The present study investigated the anxiolytic and antidepressant actions of the bioactive glycowithanolides (WSG), isolated from WS roots, in rats. WSG (20 and 50 mg/kg) was administered orally once daily for 5 days and the results were compared by those elicited by the benzodiazepine lorazepam (0.5 mg/kg, i.p.) for anxiolytic studies, and by the tricyclic anti-depressant, imipramine (10 mg/kg, i.p.), for the antidepressant investigations. Both these standard drugs were administered once, 30 min prior to the tests. WSG induced an anxiolytic effect, comparable to that produced by lorazepam, in the elevated plus-maze, social interaction and feeding latency in an unfamiliar environment, tests. Further, both WSG and lorazepam, reduced rat brain levels of tribulin, an endocoid marker of clinical anxiety, when the levels were increased following administration of the anxiogenic agent, pentylenetetrazole. WSG also exhibited an antidepressant effect, comparable with that induced by imipramine, in the forced swim-induced 'behavioural despair' and 'learned helplessness' tests. The investigations support the use of WS as a mood stabilizer in clinical conditions of anxiety and depression in Ayurveda. Altern Med Rev. 2000 Aug;5(4):334-46. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. OBJECTIVE: The objective of this paper is to review the literature regarding Withania somnifera (ashwagandha, WS) a commonly used herb in Ayurvedic medicine. Specifically, the literature was reviewed for articles pertaining to chemical properties, therapeutic benefits, and toxicity. DESIGN: This review is in a narrative format and consists of all publications relevant to ashwagandha that were identified by the authors through a systematic search of major computerized medical databases; no statistical pooling of results or evaluation of the quality of the studies was performed due to the widely different methods employed by each study. RESULTS: Studies indicate ashwagandha possesses anti-inflammatory, antitumor, antistress, antioxidant, immunomodulatory, hemopoietic, and rejuvenating properties. It also appears to exert a positive influence on the endocrine, cardiopulmonary, and central nervous systems. The mechanisms of action for these properties are not fully understood. Toxicity studies reveal that ashwagandha appears to be a safe compound. CONCLUSION: Preliminary studies have found various constituents of ashwagandha exhibit a variety of therapeutic effects with little or no associated toxicity. 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. Ethnopharmacol. 2000 Apr;70(1):57-63. Adaptogenic and cardioprotective action of ashwagandha in rats and frogs. Pharmacological and metabolic effects of ashwagandha (Withania somnifera L. (Solanaceae)) used in Ayurveda as a herbal tonic and health food were studied. Ashwagandha was shown to increase swimming time in rats in physical working capacity test, i.e. rats swimming endurance test. Significant increase in relative heart weight and glycogen content in myocardium and liver was also observed in ashwagandha treated group. Ashwagandha treatment increased the duration of contractility in functional test for the resistance of frog heart muscle towards the toxic action of strophanthin-K. Ashwaaandha treatment also resulted in significant increase in coagulation time which attains normalcy 7 days after cessation of treatment. Ashwagandha possesses no toxicity up to a dose of (100 mg/kg; p.o. for 180 days) and does not cause significant changes in biochemical parameters in the blood serum of rats. Increase in catecholamine content in the heart and aortic tissues and their decrease in adrenal glands are unfavourable effects of high doses of ashwagandha. On the basis of these observations, it was concluded that ashwagandha possesses adaptogenic, cardiotropic, cardioprotective and anticoagulant properties. J Ethnopharmacol. 1999 Oct;67(1):27-35. Studies on immunomodulatory activity of Withania somnifera (Ashwagandha) extracts in experimental immune inflammation. The immunomodulatory activities of an Indian Ayurvedic medicinal preparation, i.e. extracts from Ashwagandha, Withania somnifera (L.) Dunal (Solanaceae), namely WST and WS2, were studied in mice for immune inflammation: active paw anaphylaxis and delayed type hypersensitivity (DTH). Immunomodulatory effect was assessed in If IgE-mediated anaphylaxis as reduction of ovalbumin-induced paw edema, in animals treated with WS2 at doses of 150 and 300 mg/kg, and the results were compared with the standard drug disodium chromoglycate. In the DTH model, the modulatory effect was assessed as potentiation or suppression of the reaction, revealing an increase or decrease in mean foot pad thickness, respectively. Potentiation of the DTH reaction was observed in animals treated with cyclophosphamide at a dose of 20 mg/kg, WST at a dose of 1000 mg/kg and WS2 at a dose of 300 mg/kg. On the other hand, cyclophosphamide-induced potentiation of DTH reaction was suppressed in animals treated with WST and WS2. A significant increase in white blood cell counts and platelet counts was observed in animals treated with WST. A protective effect in cyclophosphamide-induced myelosuppression was observed in animals treated with WST and WS2, revealing a significant increase in white blood cell counts and platelet counts. Cyclophosphamide-induced immunosuppression was counteracted by treatment with WS2, revealing significant increase in hemagglutinating antibody responses and hemolytic antibody responses towards sheep red blood cells. J Pharm Pharmacol. 1998 Sep;50(9):1065-8. Changes in thyroid hormone concentrations after administration of ashwagandha root extract to adult male mice. The importance of ashwagandha root extract in the regulation of thyroid function with special reference to type-I iodothyronine 5'-monodeiodinase activity in mice liver has been investigated. Although the root extract (1.4 g kg(-1)) administered daily for 20 days by gastric intubation increased serum 3,3',5-triiodothyronine (T3) and tetraiodothyronine (T4) concentrations and hepatic glucose-6-phosphatase activity, hepatic iodothyronine 5'-monodeiodinase activity did not change significantly. Furthermore, ashwagandha root extract significantly reduced hepatic lipid peroxidation, whereas the activity of antioxidant enzymes such as superoxide dismutase and catalase were increased. These findings reveal that the ashwagandha root extract stimulates thyroidal activity and also enhances the antiperoxidation of hepatic tissue. Immunopharmacol Immunotoxicol. 1998 Feb;20(1):191-8 Therapeutic efficacy of Ashwagandha against experimental aspergillosis in mice. Therapeutic efficacy of an Indian Ayurvedic medicinal preparation, Ashwagandha [Withania somnifera L. Dunal (Solanceae; root)] was evaluated against experimental aspergillosis in Balb/c mice. Ashwagandha given orally once daily for 7 consecutive days in a dose of 100 mg/kg after intravenous infection of Aspergillus fumigatus prolonged the survival period of infected mice. This protective activity was probably related to the observed increases in phagocytosis and intracellular killing of peritoneal macrophages induced by Ashwaganda treatment. The number of peripheral leukocytes was not modified, excluding a possibility of mobilization of cells from other compartments. On the basis of these findings, the probable mechanism underlying the protective action of Ashwagandha against systemic Aspergillus infection was discussed in relation with its possible activity to activate the macrophage function. J Ethnopharmacol. 1994 Dec;44(3):131-5 A comparative pharmacological investigation of Ashwagandha and Ginseng. 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). Indian J Exp Biol. 1992 Mar;30(3):169-72 In vivo growth inhibitory effect of Withania somnifera (Ashwagandha) on a transplantable mouse tumor, Sarcoma 180. 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. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=26323