SYSTEMIC ADMINISTRATION OF DEFINED EXTRACTS FROM WITHANIA-SOMNIFERA (INDIAN GINSENG) AND SHILAJIT DIFFERENTIALLY AFFECTS CHOLINERGIC BUT NOT GLUTAMATERGIC AND GABAERGIC MARKERS IN RAT-BRAIN

Although some promising results have been achieved by acetylcholineste rase inhibitors, an effective therapeutic intervention in Alzheimer's disease still remains an important goal. Sitoindosides VII-X, and with aferin-A, isolated from aqueous methanol extract from the roots of cul tivated 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 attenua te cerebral functional deficits, including amnesia, in geriatric patie nts. The present investigation was conducted to assess whether the mem ory-enhancing effects of plant extracts from Withania somnifera and Sh ilajit are owing to neurochemical alterations of specific transmitter systems. Therefore, histochemistry to analyse acetylcholinesterase act ivity as well as receptor autoradiography. to detect cholinergic, glut amatergic and GABAergic receptor subtypes were performed in brain slic es 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 bo dy weight for 7 days. Administration of Shilajit led to reduced acetyl cholinesterase staining; restricted to the basal forebrain nuclei incl uding medial septum and the vertical limb of the diagonal band. System ic application of the defined extract from Withania somnifera, however , led to differential effects on AChE activity in basal forebrain nucl ei: slightly enhanced AChE activity was found in the lateral septum an d globus pallidus, whereas in the vertical diagonal band AChE activity was reduced following treatment with sitoindosides VII-X and withafer in-A. These changes were accompanied by enhanced M(1)-muscarinic choli nergic receptor binding in lateral and medial septum as well as in fro ntal cortices, whereas the M(2)-muscarinic receptor binding sites were increased in a number of cortical regions including cingulate, fronta l, piriform, parietal and retrosplenial cortex. Treatment with Shilaji t or the defined extract from Withania somnifera affected neither GABA (A) and benzodiazepine receptor binding nor NMDA and AMPA glutamate re ceptor 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 foreb rain cholinergic signal transduction cascade. The drug-induced increas e in cortical muscarinic acetylcholine receptor capacity might partly explain the cognition-enhancing and memory improving effects of extrac ts from Withania somnifera observed in animals and humans. Copyright ( C) 1996 Elsevier Science Ltd