{"paper_id":"0834f491-4a6b-4bc6-8724-e331ec11387d","body_text":"J. Pharm. Pharmacogn. Res., vol. 13, Supplement 1, pp. S140-S152, Apr 2025.\nDOI: https://doi.org/10.56499/jppres24.2238_13.s1.140Original Article\nNetwork pharmacology and molecular docking of Phaleria macrocarpa (Scheff.) Boerl. bioactive compounds involved in endometriosis pathway\n[Farmacología en red y acoplamiento molecular de compuestos bioactivos de Phaleria macrocarpa (Scheff.) Boerl. implicados en la vía de la endometriosis]\nSutrisno Sutrisno1,2*, Maharani Maharani3\n1Department of Obstetrics and Gynaecology, Faculty of Medicine, Universitas Brawijaya/ Saiful Anwar General Hospital, Malang, East Java, Indonesia.\n2Master Program of Midwifery, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, Indonesia.\n3Department of Midwifery, Polytechnic of Health-Ministry of Health, Aceh, Indonesia.\n*E-mail: snospog.fk@ub.ac.id\nAbstract\nContext: Endometriosis is the presence of endometrial glands and stromal lesions outside the uterus.\nAims: To investigate the network pharmacology and molecular docking of Phaleria macrocarpa bioactive compounds on selected endometriosis pathways.\nMethods: 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.\nResults: 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.\nConclusions: 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.\nKeywords: angiogenesis; endometriosis; inflammation; pathomechanisms; proliferation.\nResumen\nContexto: La endometriosis se define como la presencia de glándulas endometriales y lesiones estromales fuera del útero.\nObjetivos: Investigar la farmacología en red y la unión molecular de los compuestos bioactivos de Phaleria macrocarpa en vías específicas de la endometriosis.\nMétodos: Los compuestos de P. macrocarpa se obtuvieron de PubChem. Se analizó el potencial de los compuestos mediante la predicción WAY2DRUG PASS. Las dianas proteicas se predijeron utilizando las bases de datos Comparative Toxicogenomic Database (CTD), STITCH y Open Target. El análisis de redes farmacológicas se realizó con STRING. Se realizó un análisis de acoplamiento molecular entre ácido tolfenámico, naringenina, eriodictiol, 5-O-metilgenisteína y 8-prenilnaringenina frente a la proteína postraglandina-endoperóxido sintasa 2/ciclooxigenasa-2 (PTGS2/COX-2) y el receptor de progesterona (PGR) utilizando AutoDock Vina integrado en PyRx v.0.9.8. La visualización se realizó con el software BioVia Discovery Studio 2019.\nResultados: En la vía PTGS/COX-2, los compuestos con mayor afinidad para la interacción son el ácido tolfenámico y la naringenina. Frente al PGR, los fitoquímicos con mayor afinidad de interacción son la naringenina y la 8-prenilnaringenina.\nConclusiones: Según los resultados del acoplamiento molecular, se predice que los compuestos de P. macrocarpa tienen actividad como inhibidores de PTGS2/COX-2, especialmente la (±)-naringenina y el eriodictiol. La narigenina y la 8-prenilnaringenina mostraron actividad sobre los PGR. En comparación con la 8-prenilnarigenina, la naringenina se une con mayor fuerza a los PGR.\nPalabras Clave: angiogénesis; endometriosis; inflamación; patomecanismos; proliferación.\nCitation Format: Sutrisno S, Maharani M (2025) Network pharmacology and molecular docking of Phaleria macrocarpa (Scheff.) Boerl. bioactive compounds involved in endometriosis pathway. J Pharm Pharmacogn Res 13(s1): S140–S152. https://doi.org/10.56499/jppres24.2238_13.s1.140\nReferences\nAgarwal A, Mulgund A, Hamada A, Chyatte MR (2015) A unique view on male infertility around the globe. Reprod Biol Endocrinol 13: 37. https://doi.org/10.1186/s12958-015-0032-1\nAhmad R, Mazlan MKN, Aziz AFA, Gazzali AM, Rawa MSA, Wahab HA (2023) Phaleria macrocarpa (Scheff.) Boerl.: An updated review of pharmacological effects, toxicity studies, and separation techniques. 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