INTEGRATED NETWORK PHARMACOLOGY AND IN VIVO VALIDATION OF SILYMARIN AS A NEUROPROTECTIVE AGENT AGAINST ALCOHOL WITHDRAWAL-INDUCED COGNITIVE DYSFUNCTION

Abstract

Abnormal limbic memories result from alcohol abuse, and can contribute to greater alcohol intake and relapse. Those suffering from AWS might suffer from withdrawal symptoms both physically and psychologically, such as memory problems. The therapeutic effects of silymarin on memory dysfunction was investigated in the present study by the network pharmacology method. Nine active compounds were found in silymarin, 69 molecular targets and 12 metabolic pathways were found. The genes PTPN1, DPP4, CA7, CA4, GUS, GALR3 and HSP90AB1 were identified to suppress symptoms of memory impairments and activity of the synapses of the serotonergic and glutamatergic systems. Silymarin was studied for 7 days after 21 days of chronic alcohol therapy for effect on memory dysfunction caused by alcohol withdrawal from male wistar rats. Morris Water Maze Test &  New Object Recognition Test employed to measure memory impairments due to alcohol withdrawal. Oxidative Parameters (MDA, NO) & antioxidant enzyme parameters (SOD, GSH, CAT) were performed. A histopathological study of Rat's brain was carried out. The data were analysed by One-way and Two-way ANOVA and Tukey & Bonferroni's post hoc test. The silymarin-treated rats significantly enhanced the learning and spatial memory, as compared to the ethanol-treated rats. But treatment with silymarin led to a decrease of MDA and NO, and an increase of SOD, GSH, and CAT. Histopathologists found that silymarin treated neurons were unaffected in the brain from alcohol withdrawal. Based on the findings of the study, silymarin can be used as an anti-alcohol withdrawal memory dysfunction antioxidant.