Resveratrol modulates NMDAR-nNOS axis in the cerebellum of a neuroexcitotoxic model of Hepatic encephalopathy

Resveratrol (RSV), a natural plant derived phytoalexin, is known to exhibits its biological activity by activating Sirt1 which confers neuroprotection under a variety of neurological complications like ischemia, Alzheimer’s disease etc. Hepatic Encephalopathy (HE) is a disorder of mental activity, neuromuscular function and consciousness that occurs as a result of liver dysfunction, involving Nmethyl-D-aspartate receptor (NMDAR) over activation in brain cells, causing excitotoxicity. Therapeutic modulation of this glutamate receptor, therefore,needs to be investigated to define cerebral mechanism based management of HE. This article evaluates the effect of RSV as herbal supplement in modulation of NMDAR-nNOS (neuronal nitric oxide synthase) axis in the cerebellum of rats with moderate grade HE (MoHE) induced by administration of 100 mg/kg b.w. of thioacetamide i.p. for 10 days. In another set, the MoHE rats were co-treated with RSV 10mg/Kg bw i.p from 8th day of TAA treatment up to 14 days.As compared to the NR2A dominated NMDAR composition observed in the cerebellum of the control rats, the MoHE rats showedenhanced NR2B dominated NMDAR expression. The level of nNOS and NO are considered as a biochemical assay for the NMDAR activity. Both, nNOS expression and NO levels, as compared to the control rats, were found to be enhanced in the cerebellum of the MoHE rats. However, all these parameters were observed to regain their normal levels in the cerebellum of the MoHE rats treated with RSV. The findings suggest that resveratrol could act as a neuroprotectant against MoHE pathogenesis by modulating NMDARnNOS axis in cerebellum.