Integrated Network Pharmacology, In Silico Analysis, and Experimental Validation to Reveal Antidiarrheal Activity of...

Psidium guajava L. (guava) is a well-known equatorial plant exploited for food and medicinal purposes. The present study is based on the antidiarrheal activity of the hydroalcoholic extract of its leaves in castor oil-induced diarrhea.

The extract was analysed by GC-MS, and secondary metabolites were identified. The pharmacokinetic analysis and toxicity profiling of the identified components were performed. The network pharmacological analysis was performed to find compound-key target interaction pathways. In silico docking analysis was performed against epidermal growth factor receptor (EGFR) and prostaglandin E receptor 3 (EP3), and ligand binding efficiency was calculated. The diarrheal model was developed by administering castor oil and evaluated antidiarrheal activities using loperamide as a standard drug.

GC-MS identified major compounds that were screened for physicochemical properties and toxicity profiling, and network pharmacological pathways were established. GC-MS identified compounds such as α-cubebene, caryophyllene, and ipriflavone, which were computationally docked with key proteins EGFR and ER3.

The docking study exhibited good binding energy and ligand efficiency. The animals were administered different doses of extracts, and their antidiarrheal effect was appraised via castor oil-induced diarrhea, charcoal meal assay, and the in vivo antidiarrheal index was calculated.

Further, histopathological analysis of the ileal tissue of the small intestine was conducted to support its diarrheal protection effect.