Anti-diarrhoea properties of ethanol extract of Citrullus colocynthis fruit pulp: in vivo and in silico studies

Abstract

This study aimed to establish anti-diarrhoea agents, through in vivo and in silico molecular modelling from the phytoconstituents of Citrullus colocynthis ethanol fruit pulp extract (CCEFPE). The crystal structure of µ (mu) opioid and aquaporin 4 (AQP4) receptors were retrieved from the RCSB database, while the identified compounds from C. colocynthis ethanol fruit pulp extract were sequentially docked via Schrödinger suite. In CCEFPE in vivo anti-diarrhoea studies, control received distilled water (2 mL/kg, p.o.), diarrhoea was administered with castor oil or MgSO₄ (2 mL/kg, p.o.), standard drug was administered 2 mg/kg, p.o. loperamide, while CCEFPE (50, 100 and 150 mg/kg, p.o.) was administered to the treated groups. Seven hit compounds out of which 54 displayed relatively higher free binding energy for mu opioid and AQP4. Swiss ADME predicted compounds 54 to be blood–brain impermeant, have low gastrointestinal absorption, strong druglike-ness, and safety profile among the hits. In the in vivo study, the onset of diarrhoea was significantly (p < 0.05) delayed by CCEFPE. A significant reduction (p < 0.05) in gastrointestinal motility, enteropooling and PGE₂ in diarrhoea-induced groups was also observed after CCEFPE administration. Compound 54, even though it has drug-like properties, displayed a weak interaction with the receptor and hence can be structurally modified to an analogue of loperamide for a better ligand-receptor interaction while the in vivo studies confirmed the anti-diarrhoea activities of C. colocynthis ethanol fruit pulp extract.