Integrated Network Pharmacology, In Silico Analysis, and Experimental Validation to Reveal Antidiarrheal Activity of Psidium guajava L. Leaf Extract.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: 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.

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