Systemic administration of defined extracts from Withania somnifera (Indian Ginseng) and Shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain
by
Schliebs R, Liebmann A, Bhattacharya SK, Kumar A, Ghosal S, Bigl V.
Paul Flechsig Institute for Brain Research,
Department of Neurochemistry,
University of Leipzig, Germany.
Neurochem Int 1997 Feb;30(2):181-90
ABSTRACT
Although some promising results have been achieved
by acetylcholinesterase inhibitors, an effective therapeutic intervention
in Alzheimer's disease still remains an important goal. Sitoindosides VII-X,
and withaferin-A, isolated from aqueous methanol extract from the roots
of cultivated varieties of Withania somnifera (known as Indian Ginseng),
as well as Shilajit, a pale-brown to blackish brown exudation from steep
rocks of the Himalaya mountain, are used in Indian medicine to attenuate
cerebral functional deficits, including amnesia, in geriatric patients.
The present investigation was conducted to assess whether the memory-enhancing
effects of plant extracts from Withania somnifera and Shilajit are owing
to neurochemical alterations of specific transmitter systems. Therefore,
histochemistry to analyse acetylcholinesterase activity as well as receptor
autoradiography to detect cholinergic, glutamatergic and GABAergic receptor
subtypes were performed in brain slices from adult male Wistar rats, injected
intraperitoneally daily with an equimolar mixture of sitoindosides VII-X
and withaferin-A (prepared from Withania somnifera) or with Shilajit, at
doses of 40 mg/kg of body weight for 7 days. Administration of Shilajit
led to reduced acetylcholinesterase staining, restricted to the basal forebrain
nuclei including medial septum and the vertical limb of the diagonal band.
Systemic application of the defined extract from Withania somnifera, however,
led to differential effects on AChE activity in basal forebrain nuclei:
slightly enhanced AChE activity was found in the lateral septum and globus
pallidus, whereas in the vertical diagonal band AChE activity was reduced
following treatment with sitoindosides VII-X and withaferin-A. 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, piriform, parietal and retrosplenial
cortex. Treatment with Shilajit or the defined extract from Withania somnifera
affected neither GABAA and benzodiazepine receptor binding nor NMDA and
AMPA glutamate receptor subtypes in any of the cortical or subcortical regions
studied. The data suggest that Shilajit and the defined extract from Withania
somnifera affect 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 extracts from Withania somnifera observed
in animals and humans.
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