Phytochemical analysis, molecular docking and antiamnesic effects of methanolic extract of Silybum marianum (L.) Gaertn seeds in scopolamine induced memory impairment in mice.

Ethnopharmacological relevance: Silybum marianum (L.) Gaertn and its main component silymarin have been extensively studied and have been found effective in various neurological disorders. Aims of the study: The aim of the current study is to identify phytoconstituents in the methanolic extract (Me. Ext) of Silybum marianum (L.) Gaertn seeds and to study in-vivo the anti-amnesic effects along with in vitro antioxidant and acetylcholinesterase (AChE) and buteryl cholinesterase (BChE) inhibition potential. Induced fir docking (IFD) results have confirmed that quercetin, morin and rutin showed good affinity when docked into AChE binding site. Materials and methods: The present study investigates the in-vitro AChE and BChE inhibition potential of the Me-Ext of Silybum marianum (L.) Gaertn at various concentrations (31.25, 62.50, 125, 250, 500, 1000 mu g/mL) using Ellman's spectrophotometric analysis, while antioxidant potential against DPPH and ABTS were determined using Brand-Williams spectrophotometric method. Furthermore, the in-vivo anti-amnesic effects of Me. Ext at the dose level of 50, 100 and 200 mg/kg were also evaluated using scopolamine-induced memory impairment in mice in the novel object recognition test (NORT) and Y-maze test. Results: The Me. Ext showed a concentration dependent inhibition of AChE and BChE with IC50 values of 110 and 130 mu g/mL respectively and antioxidant activity against DPPH and ABTS with IC50 values 280 and 220 mu g/mL, respectively. In mice, Me. Ext reversed the amnesia induced by scopolamine as indicated by a dose dependent increase in spontaneous alternation performance in the Y-maze task (p < 0.05 versus scopolamine) and increase in the discrimination index in the NORT comparable to the standard drug donepezil 2 mg/kg. HPLC-UV analysis showed the presence of quercetin, rutin and morin. Induced fit docking (IFD) was performed using quercetin, rutin and morin, Glide Gscore and IFD score of all compounds were consistent with their experimental AChE inhibitory activities. Conclusion: The results indicate that Silybum marianum (L.) Gaertn could be a new source for the isolation of phytoconstituents useful in cognition and memory disorders such as Alzheimer's disease.