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We explored the ameliorating effect of naringenin in PCOS using the Sprague Dawley (SD) rat model and human granulosa cells. Letrozole\u2010induced PCOS rats were given either naringenin (50\u2009mg\/kg\/day) alone or in combination with metformin (300\u2009mg\/kg\/day), followed by the estrous cycle, hormonal analysis, and glucose sensitivity test. To evaluate the effect of naringenin on granulosa cell (hGC) steroidogenesis, we treated cells with naringenin (2.5\u2009\u03bcM) alone or in combination with metformin (1\u2009mM) in the presence of forskolin (10\u2009\u03bcM). To determine the steroidogenesis of CYP\u201017A1, \u201019A1, and 3\u03b2HSD2, the protein expression levels were examined. Treatment with naringenin in the PCOS animal groups increased ovulation potential and decreased cystic follicles and levels of androgens. The expression levels of CYP\u201017A1, \u201019A1, and 3\u03b2HSD2, were seen restored in the ovary of PCOS SD rats' model and in the human ovarian cells in response to the naringenin. We found an increased expression level of phosphorylated\u2010AKT in the ovary and hGCs by naringenin. Naringenin improves ovulation and suppress androgens and cystic follicles, involving AKT activation.<\/jats:p>","DOI":"10.1002\/ptr.7860","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T07:08:52Z","timestamp":1683788932000},"page":"4018-4041","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Naringenin improves ovarian health by reducing the serum androgen and eliminating follicular cysts in letrozole\u2010induced polycystic ovary syndrome in the Sprague Dawley rats"],"prefix":"10.1002","volume":"37","author":[{"given":"Rumaisa","family":"Rashid","sequence":"first","affiliation":[{"name":"Endocrinology Division CSIR\u2010Central Drug Research Institute  Lucknow India"},{"name":"Department of Pharmaceutical Sciences University of Kashmir  Jammu and Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupal","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Endocrinology Division CSIR\u2010Central Drug Research Institute  Lucknow India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akanksha","family":"Singh","sequence":"additional","affiliation":[{"name":"Endocrinology Division CSIR\u2010Central Drug Research Institute  Lucknow India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudarsan","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Endocrinology Division CSIR\u2010Central Drug Research Institute  Lucknow India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajaykumar","family":"Kawale","sequence":"additional","affiliation":[{"name":"Endocrinology Division CSIR\u2010Central Drug Research Institute  Lucknow India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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