THE EFFECTS OF WITHANIA SOMNIFERA ON RAT BRAIN CORTEX GABAA RECEPTORS MICROTRANSPLANTED INTO XENOPUS OOCYTES
Manuel Candelario1, Erika Cuellar1, Agenor Limon2, Jorge Mauricio Reyes-Ruiz2, Ricardo Miledi2, Amelia Russo-Neustadt1.
1California State University Los Angeles, Los Angeles, CA, 2University of California, Irvine, Irvine, CA.
Withania somnifera (WS), also known as ashwagandha, is an adaptogenic plant which has been used for thousands of years in Ayurvedic medicine. Experimental evidence has shown that WS has pharmacological effects on the central nervous system (CNS), showing anti-convulsive, anti-anxiolytic, and stress reducing properties. These pharmacological effects suggest that WS might function through GABAergic pathways. Indeed, recently, it was found that WS has GABA-mimetic activity probably through direct interaction with GABAA receptors. Though these are promising results, the main pharmacological activity and molecular mechanisms through which WS works are still unknown. To further elucidate the electrophysiological properties of WS on mammalian brain GABAA receptors, we prepared rat brain cortex membranes and microtransplanted them into Xenopus oocytes. We evaluated, 24 to 48 hours later, the electrophysiological effects of distinct WS root powder preparations (decoction, infusion, and dissolved solution, 3 commonly used preparations in traditional Ayurvedic medicine) on GABAA receptors. The mode of extraction seems to play a critical role in the composition and activity of the extracts. Our results show that the optimal WS preparation, infusion, had an EC value of 4.68 mg/mL (p-value = 3.81). Here we demonstrate a dose-dependent effect of WS root on GABAA ionotropic receptors. In addition, we were able to observe complex effects of WS as a GABA agonist and a partial inhibitor. Our data supports a complex modulatory effect on the CNS by WS.