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In this study, we applied an integrated in silico strategy combining network pharmacology, protein\u2013protein interaction analyses, molecular docking, 100\u2010ns molecular dynamics simulations, and single\u2010cell transcriptomic data to identify potential trigonelline targets relevant to ovarian aging. Among 57 predicted targets, five (MMP9, JAK2, PARP1, HDAC1, and CYP3A4) emerged as core candidates spanning extracellular matrix remodeling, genome and epigenome maintenance, and endocrine\/xenobiotic metabolism. Structural and molecular dynamics simulations combined with single\u2010cell expression patterns converged on PARP1 and MMP9 as the most plausible central mediators of trigonelline's putative age\u2010modulating effects in the ovary, with JAK2 and HDAC1 as intermediate candidates and CYP3A4 as a likely systemic mediator. These exploratory findings provide a conceptual framework that links coffee\u2010derived trigonelline to molecular pathways of ovarian aging and highlight specific targets and pathways for experimental validation in future nutrition and reproductive\u2010aging studies.<\/jats:p>","DOI":"10.1002\/fsn3.71421","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T08:17:02Z","timestamp":1770711422000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["From Coffee Alkaloid to Ovarian Targets: An Integrated Computational Framework for Trigonelline in Ovarian Aging"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0926-7942","authenticated-orcid":false,"given":"Woon Shin","family":"Yong","sequence":"first","affiliation":[{"name":"Department of Gynecology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai 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