Molecular docking of flavonoids from Phaleria macrocarpa on the NF-kB p65, VEGFR2, Ki67, COX-2, and CXCR4 pathways in endometriosis

• Published in: Journal of pharmacy & pharmacognosy research 2025-03, Vol.13 (2), p.527-537
• Main Authors: Maharani, Maharani, Sutrisno, Sutrisno, Wiyasa, I Wayan Arsana, Winarsih, Sri, Soeharto, Setyawati, Indrawan, I Wayan Agung, Endharti, Agustina Tri
• Format: Article
• Language: English
• ISSN: 0719-4250; 0719-4250
• DOI: 10.56499/jppres24.2090_13.2.527

Context: Endometriosis is a condition marked by the presence of endometrial epithelium and stromal cells outside the uterus. Previous studies have shown that prostaglandin E2 has a role in the development of endometriosis via the action of local estrogen and estrogen receptors. Aims: To analyze the molecular docking between Phaleria macrocarpa flavonoid compounds in the NF-B, VEGF/VEGFR2, Ki67, COX-2, and CXCR4 pathways that are involved in the pathomechanism of endometriosis. Methods: Functional determination of Phaleria macrocarpa phytochemistry using PASS prediction ADMETSAR's prediction of Phaleria macrocarpa's flavonoids compounds meet the Lipinski rule criteria so that they are predicted to have drug-likeness and no toxicity. Phaleria macrocarpa flavonoids were synthesized using AutoDock Tools 1.5.7 software. AutoDock Vina v1.2.3 software was used to perform docking simulations of ligands and target proteins. The results of the docking analysis were visualized with the Discovery Studio 4.1 application. Results: For the NF-B pathway, the compounds that showed the highest affinity for interaction to occur were (±)-naringenin (target of NF-B p50/p65) and (-)-8-prenylnaringenin (the ATP-binding site in IKK). Against VEGF-A and VEGFR2, the flavonoids that exhibited the highest interaction affinity were glycitin, and (-)-8-prenylnaringenin, respectively. The compound that interacted most easily with Ki67, COX-2, or CXCR4 was (+)-catechin 7-O-beta-D-xyloside. For docking with standard drugs, we found that leuprolide acetate and dienogest showed higher affinity for NF-B p50/p65 heterodimer than flavonoids. Conclusions: The six compounds Phaleria macrocarpa have different affinities for selected pathways in endometriosis. Thus, the Phaleria macrocarpa flavonoids could be a multi-action herbal candidate for endometriosis, which can be used alone or as a complement to standard drugs.