Guduchi Sawras (Tinospora cordifolia): An Ayurvedic drug treatment modulates the impaired lipid metabolism in alcoholics through dopaminergic neurotransmission and anti-oxidant defense system.

Tinospora cordifolia (Guduchi Sawras) though has been clearly demonstrated in literature for its hypolipidemic and anti-alcoholism properties but its anti-hyperlipidemia mechanistic approach is still missing. Moreover, its direct implication with alcohol induced hyperlipidemia has also not been reported till date. In order to explore the answers of these questions, phytochemicals of Tinospora cordifolia water extract "Guduchi Sawras" (GS) was analyzed using HPLC-Q-TOF-MS. On the basis of relative peak volumes 110 compounds were selected and identified in GS. Besides that, protein targets of most abundant compounds present in GS were fetched from ChEMBL and protein interaction network (PIN) was constructed. GO enrichment analysis showed that GS targets various pathways including dopamine metabolism, cAMP-dependent signaling pathway, and glycolytic process. Biological processes obtained via PIN were correlated with hyperlipidemia markers and dopamine metabolism in moderate alcohol consumers (n=25) and healthy volunteers (n=27) of age 41±3.8years. Metabolic analysis demonstrated the increased serotonin (1.9-fold) and decreased dopamine (-2.3-fold) levels in alcoholics. Further data analysis revealed a significant increase in urinary BCAAs (>2.0-fold), pantothenic acid (1.8-fold), carnitines (>2-fold) levels, and decrease in PPARα activation markers levels i.e. nicotinamide-1-oxide (-1.7-fold), and N-methylnicotinamide (-1.6-fold) in alcoholics. Biochemical analysis showed the increased AST/ALT ratio (1.91), along with triglycerides (20%), and MDA (34%) and GSH (56%) levels in alcoholics. GS treatment significantly reverted the most of the discussed metabolites levels (p<0.05) and enzymes activities (p<0.05) in alcoholics. The data depict that moderate chronic alcohol consumption lead to hyperlipidemia and oxidative burden; whereas GS treatment ameliorates hyperlipidemia by decreasing oxidative stress, activating PPARα, CREB and SREBP-1 through stimulation of dopamine D1 receptors mediated signalling molecules i.e. cAMP and protein kinase A.