Experimental validation and network pharmacology evaluation to decipher the mechanism of action of Erythrina variegata L. bark against scopolamine-induced memory impairment in rats

Abstract

This paper aimed to elucidate the effect of Erythrina variegata L. bark on scopolamine-induced memory impairment in rats and to decipher the molecular mechanism of phytoconstituents via the utilization of gene set enrichment analysis, network pharmacology coupled with in silico docking study. First, three models i.e. Morris Water Maze (MWM), Elevated Plus Maze (EPM), and Passive Avoidance Paradigm (PA) were utilized to elucidate the memory function. Second, the level of biomarkers i.e. acetylcholinesterase enzyme, reduced glutathione, and lipid peroxidation level were measured in brain tissues. Third, the key bioactive phytoconstituents targeting potential protein targets and pathways were identified through gene set enrichment analysis and network pharmacology. Lastly, the interaction between bioactive phytoconstituents with their respective targets was confirmed by molecular docking analysis. The MWM, EPM, and PA activity showed, scopolamine administration increased Escape Latency Time (ELT), Transfer Latency (TL), and Step Through Latency (STL) respectively on day 0th, 7th, 14th, and 21st, whereas treatment with E. variegata extract significantly reverse the ELT, TL and STL activity. The decreased level of Acetylcholinesterase (AChE) and MDA level in treated animals reflected the enhanced memory and was found to be comparable withclinically proven drug i.e. donepezil. Sixty compounds were identified in EV bark, among which twenty-two compounds are predicted to modulate potential targets involved in AD and considered potentially bioactive. Further, the docking study revealed, Alpinumisoflavone, Auriculatin, Osajin, and Scandenone to have the highest binding affinity with Tau protein, Whereas Donepezil and Glucoerysodine with acetylcholinesterase enzyme.