Ameliorative Antidiarrheal Potential of Momordica Charantia Leaves Extract: In Silico and In Vivo Approach

Abstract

Objective: Poor tolerance, adverse effects, and the emergence of multidrug resistance are common limitations of the pharmacological therapies for diarrhea now available. Particularly in children, diarrhea continues to be a major source of morbidity and mortality. Methods: This work used both in silico and in vivo approaches to investigate the antidiarrheal potential of a hydroalcoholic (50:50) extract of Momordica charantia leaves (MCLE), with a focus on human δ-opioid receptor (hDOR) regulation. Molecular docking and in silico ADMET studies were conducted on the primary bioactive constituents of M. charantia, including charantal, cucurbitacins, epoxy-cucurbitans, momordicine I, momordicoside I, momordicoside K, and β-sitosterol. Swiss ADME research revealed that momordicine I and Charantal were drug-like candidates with a high expected gastrointestinal absorption and no violations of the Lipinski rule. Results: Docking against hDOR (PDB ID: 4EJ4) revealed strong binding affinities for momordicoside I (−8.33 kcal/mol), β-sitosterol (−8.27 kcal/mol), and momordicine I (−8.0 kcal/mol). These affinities demonstrated efficient peripheral δ-opioid receptor antagonism, since they were much greater than those of the reference drug loperamide (−7.57 kcal/mol). The in vivo antidiarrheal efficacy of MCLE was evaluated in albinorat using models of gastrointestinal motility, enteropooling, and castor oil-induced diarrhea. At 400 mg/kg body weight, oral MCLE strongly (p<0.01) and dose-dependently impeded intestinal transit of charcoal meal (42.16%), intestinal fluid buildup (54.47% reduction), and diarrheal output (64.53%). Conclusion: Overall, the results indicate the promise of M. charantia leaf extract as a safe, plant-based candidate for the development of novel antidiarrheal therapeutics by showing that it exerts considerable antidiarrheal activity through peripheral δ-opioid receptor contact.