The potency of eriosematin E from Eriosema chinense Vogel. against enteropathogenic Escherichia coli induced diarrhoea using preclinical and molecular docking studies

Acta Trop. 2019 May:193:84-91. doi: 10.1016/j.actatropica.2019.02.025. Epub 2019 Feb 23.

Abstract

The main objective of the present study was to evaluate the potential of eriosematin E (ECM) isolated from the roots of Eriosema chinense against enteropathogenic Escherichia coli (EPEC) induced diarrhoea. ECM isolated from the bioactive chloroform fraction of E. chinense was subjected to antidiarrhoeal evaluation on rats against diarrhoea, induced by the oral suspension of EPEC. The study included evaluation of behavioral parameters for 6 h and up to 24 h of induction, followed by estimation of water content, the density of EPEC in stools and evaluation of various blood parameters. Further, the colonic and small intestinal tissues were subjected to biochemical estimations, antioxidant evaluation, determination of ion concentration, Na+/K+ -ATPase activity, pro-inflammatory cytokines assessment and histopathology. Finally, the impact of ECM on Na+/K+-ATPase was studied through molecular docking studies. Significant antidiarrhoeal potential of ECM was demonstrated at 5 and 10 mg/kg, p.o., however, ECM at 10 mg/kg, p.o. was found to be more effective, as confirmed through higher % protection, density of EPEC in stools and water content of stools. ECM also significantly increased the level of WBC, Hb, platelets and revealed restoration of altered antioxidants, pro-inflammatory cytokines (IL-1β and TNF-α) status and also reactivated the suppressed Na+/K+-ATPase activity, which was also confirmed through docking studies showing H-bonding of hydroxyl group of ECM with amino acids Asp 190, Asn 167 and Glu 169 thus, maintaining proper electrolyte balance and also prevented epithelial tissue damage. The overall effect of ECM may be attributed to the decline in the elevated level of cytokines, inhibition in nitric oxide production and reactivation of Na+/K+-ATPase activity resulting in reduced intestinal secretion.

Keywords: Antidiarrhoeal activity; Diarrhoea score; Enteropathogenic Escherichia coli; Eriosema chinense; Eriosematin E; Na(+)/K(+)– ATPase.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Cytokines / metabolism
  • Diarrhea / drug therapy*
  • Diarrhea / microbiology
  • Enteropathogenic Escherichia coli*
  • Escherichia coli Infections / complications*
  • Fabaceae*
  • Feces / chemistry
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestines
  • Plant Extracts / analysis
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Plant Roots
  • Rats
  • Sodium-Potassium-Exchanging ATPase / metabolism

Substances

  • Antioxidants
  • Cytokines
  • Plant Extracts
  • Sodium-Potassium-Exchanging ATPase