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.

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