Network pharmacology and molecular docking of Phaleria macrocarpa (Scheff.) Boerl. bioactive compounds involved in endometriosis pathway

Context: Endometriosis is the presence of endometrial glands and stromal lesions outside the uterus. Aims: To investigate the network pharmacology and molecular docking of Phaleria macrocarpa bioactive compounds on selected endometriosis pathways. Methods: P. macrocarpa compounds were obtained from PubChem. The compounds were analyzed for their potential using the WAY2DRUG PASS prediction. Protein targets were predicted using the Comparative Toxicogenomic Database (CTD), STITCH, and Open Target databases. The pharmacology network analysis was conducted using STRING. Molecular docking analysis was performed between tolfenamic acid, naringenin, eriodictyol, 5-O-methylgenistein, and 8-prenylnaringenin against postaglandin-endoperoxide synthase 2/cyclooxygenase-2 (PTGS2/COX-2) and progesterone receptor (PGR) protein using AutoDock Vina integrated into PyRx v.0.9.8. The visualization was performed using BioVia Discovery Studio 2019 software. Results: For the PTGS/COX-2 pathway, the compounds that have the highest affinity for interaction to occur are tolfenamic acid and naringenin. Against PGR, the phytochemicals with the highest interaction affinity are naringenin and 8-prenylnaringenin. Conclusions: According to the molecular docking results, P. macrocarpa compounds are predicted to have activity as PTGS2/COX-2 inhibitors, especially (±)-naringenin and eriodictyol. Narigenin and 8-prenylnaringenin showed activity to PGR. Compared to 8-prenylnarigenin, naringenin binds more strongly to PGRs.