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N2, a semi\u2010natural triterpenoid from the neem family, was already reported to have antioxidant and antiinflammatory properties in our previous report. This study investigated the anti\u2010androgenic property of N2 on testosterone\u2010induced oxidative stress in Chinese Hamster Ovarian cells (CHO) and PCOS zebrafish model. The testosterone exposure disrupted the antioxidant enzymes and ROS level and enhanced the apoptosis in both CHO cells and PCOS zebrafish. However, N2 significantly protected the CHO cells from ROS and apoptosis. N2 improved the Gonado somatic index (GSI) and upregulated the expression of the SOD enzyme in zebrafish ovaries. Moreover, the testosterone\u2010induced follicular maturation arrest was normalized by N2 treatment in histopathology studies. In addition, the gene expression studies of <jats:italic>Tox3<\/jats:italic> and <jats:italic>Denndla<\/jats:italic> in zebrafish demonstrated that N2 could impair PCOS condition. Furthermore, to confirm the N2 activity, the <jats:italic>in\u2010silico<\/jats:italic> studies were performed against PCOS susceptible genes <jats:italic>Tox3<\/jats:italic> and <jats:italic>Dennd1a<\/jats:italic> using molecular docking and molecular dynamic simulations. The results suggested that N2 alleviated the oxidative stress and apoptosis <jats:italic>in\u2010vitro<\/jats:italic> and <jats:italic>in\u2010vivo<\/jats:italic> and altered the expression of PCOS key genes.<\/jats:p>","DOI":"10.1002\/ptr.7685","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T04:45:24Z","timestamp":1669869924000},"page":"1449-1461","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Nimbin analog <scp>N2<\/scp> alleviates high testosterone induced oxidative stress in <scp>CHO<\/scp> cells and alters the expression of <i>Tox3<\/i> and <i>Dennd1a<\/i> signal transduction pathway involved in the <scp>PCOS<\/scp> zebrafish"],"prefix":"10.1002","volume":"37","author":[{"given":"Gokul","family":"Sudhakaran","sequence":"first","affiliation":[{"name":"Department of Biotechnology College of Science and Humanities, SRM Institute of Science and Technology  Chennai 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