Abstract

Background: Gut disorders present a considerable worldwide health challenge, and increasing attention is being paid to natural substances as prospective treatment agents. Objective: This research utilizes network pharmacology, molecular docking, and molecular dynamics simulations to examine the mechanisms of active compounds from Areca catechu in the treatment of gastrointestinal disorders. Methods: Employing a comprehensive methodology, we evaluated active compounds from A. catechu, conducted drug-likeness and ADMET assessments, and identified principal protein targets linked to gastrointestinal diseases. Results: Utilizing a protein-protein interaction network, gene ontology enrichment, and KEGG pathway analysis, we identified that chemicals from A. catechu are significantly associated with metabolic activities, including cholesterol metabolism, fat digestion and absorption, and the PPAR signaling pathway. Molecular docking and molecular dynamics simulations were employed to evaluate the binding affinities and stability of selected compounds with three pivotal proteins: Interleukin-6 (IL-6), Peroxisome proliferator-activated receptor gamma (PPAR-γ), and Microsomal triglyceride transfer protein large subunit (MTP). Among the compounds analyzed, catechin emerged as the most promising candidate, exhibiting the highest binding affinity and exceptional stability in inhibiting all three target proteins. Conclusion: Our findings suggest that catechin from Areca catechu holds significant potential as a therapeutic agent for gastrointestinal disorders, acting through the modulation of critical metabolic and inflammatory pathways. This study underscores the importance of natural compounds in developing novel treatments for complex gastrointestinal conditions.

Key words: Areca catechu, gut disease, molecular docking, in silico.