Identifying the mechanism of eriosematin E from Eriosema chinense Vogel. For its antidiarrhoeal potential against Shigella flexneri-induced diarrhoea using in vitro, in vivo and in silico models

The main objective of the present investigation was to mechanistically evaluate the potency of the root extract (EEC), its bioactive chloroform fraction (CEC) and eriosematin E (ECM) isolated from Eriosema chinense against Shigella flexneri-induced sub-chronic model of infectious diarrhoea using in vitro, in vivo, and in silico methods. The in vitro antibacterial activity against pathogenic strain of S. flexneri demonstrated maximum effect of ECM followed by CEC and EEC in inhibiting growth of bacteria. Further, for in vivo evaluation, was carried out by inducing diarrhoea to the rats by administering oral suspension of S. flexneri to the animals, which was followed by treatment for a period of 6 days. EEC at 200, CEC at 100 and ECM at 10 mg/kg, p.o. showed promising effect, where EEC and ECM were found to be more effective showing maximum % protection on 6th day. Results also demonstrated a significant restoration of altered antioxidants, pro-inflammatory cytokines (IL-1β and TNF-α) expression, electrolyte balance, Na⁺/K⁺-ATPase activity and was also supported by histopathological examinations. Molecular docking study revealed that, eriosematin E inactivated the protease activity of SepA, a protein secreted by Shigella, which is responsible for disruption of epithelial barrier integrity. Thus, the overall observation confirmed the role of eriosematin E from E. chinense in treatment of Shigella flexneri-induced infectious diarrhoea.

Keywords: Antidiarrhoeal activity; Diarrhoea score; Eriosema chinense; Eriosematin E; SepA; Shigella flexneri.