{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:54:00Z","timestamp":1791287640895,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173883"],"award-info":[{"award-number":["82173883"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Polycystic ovary syndrome (PCOS) is a common endocrine disorder, and its treatment remains a significant challenge. This study investigated the mechanism of Jujuboside A (JuA) in the treatment of PCOS through mitophagy. Granulosa cells (GCs) were collected from follicular fluid derived from PCOS women. The effects of JuA on PCOS were determined by measuring body weight, ovarian weight, estrous cycle, glucose level, insulin tolerance, and ovarian morphology in dehydroepiandrosterone\u2010induced mice. SIRT3 expression levels were quantified in GCs, KGN cells, and mouse ovaries. The effects of JuA on SIRT3\u2010related oxidative stress and mitochondrial damage were investigated in KGN cells and mice. Transmission electron microscopy was used to observe mitochondrial damage and mitophagy in GCs. The expression of mitophagy\u2010related proteins (PINK1 and Parkin) was analyzed. JuA significantly improved body weight, estrous cycle, ovarian morphology, glucose tolerance, and insulin resistance, partially restoring ovarian function in PCOS mice. Moreover, JuA significantly activated SIRT3 expression and alleviated SIRT3\u2010related oxidative stress and mitochondrial damage in mouse ovaries, GCs, and KGN cells. Mechanistically, JuA upregulated SIRT3 and inhibited excessive activation of the PINK1\/Parkin pathway to reduce mitophagy. These findings demonstrated JuA protected GCs from mitochondrial damage by activating SIRT3 and inhibiting PINK1\/Parkin\u2010mediated mitophagy.<\/jats:p>","DOI":"10.1002\/mrd.70150","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:22:11Z","timestamp":1791285731000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Jujuboside a Improves Polycystic Ovary Syndrome Through SIRT3\u2010Mediated PINK1\/Parkin\u2010Dependent Mitochondrial Autophagy in Ovarian Granulosa Cells"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5744-8668","authenticated-orcid":false,"given":"Nan","family":"Zhou","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0198-5310","authenticated-orcid":false,"given":"Jiahao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First People's Hospital of Changzhou Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Lv","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Tai","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyan","family":"Xie","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"He","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7505-5001","authenticated-orcid":false,"given":"Nan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First People's Hospital of Changzhou Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2821-1013","authenticated-orcid":false,"given":"Xueyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"issue":"1","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1530\/REP-13-0386","article-title":"AKT Is Involved in Granulosa Cell Autophagy Regulation via mTOR Signaling During Rat Follicular Development and Atresia","volume":"147","author":"Choi J.","year":"2014","journal-title":"Reproduction"},{"issue":"7","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1093\/jpp\/rgad057","article-title":"Jujuboside A Ameliorates Cognitive Deficiency in Delirium Through Promoting Hippocampal E4BP4 in Mice","volume":"75","author":"Du J.","year":"2023","journal-title":"Journal of Pharmacy and Pharmacology"},{"issue":"5","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/s41419-020-2578-x","article-title":"SMAD4 Activates Wnt Signaling Pathway to Inhibit Granulosa Cell Apoptosis","volume":"11","author":"Du X.","year":"2020","journal-title":"Cell Death and Disease"},{"issue":"1","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s10815-023-02967-w","article-title":"In Vitro Evaluation of Exocytosis\u2010Associated SNARE Molecules in Human Granulosa Cells in Polycystic Ovary Syndrome","volume":"41","author":"Erol S.","year":"2024","journal-title":"Journal of Assisted Reproduction and Genetics"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2023.117698","article-title":"Traditional Chinese Medicine Formulae: A Complementary Method for the Treatment of Polycystic Ovary Syndrome","volume":"323","author":"Fu L. W.","year":"2024","journal-title":"Journal of Ethnopharmacology"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2023.116204","article-title":"Research Progress of Quality Control for the Seed of Ziziphus Jujuba Var. Spinosa (Bunge) Hu Ex H.F. Chow (Suan\u2010Zao\u2010Ren) and its Proprietary Chinese Medicines","volume":"307","author":"Gong L.","year":"2023","journal-title":"Journal of Ethnopharmacology"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","DOI":"10.1155\/2020\/5861821","article-title":"Botanical and Traditional Uses and Phytochemical, Pharmacological, Pharmacokinetic, and Toxicological Characteristics of Ziziphi Spinosae Semen: A Review","volume":"2020","author":"He S. 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Oxidative Stress and Glucose Metabolism via Mitochondrial Sirtuin 3 Signaling","volume":"109","author":"Zhang Q.","year":"2023","journal-title":"Phytomedicine"},{"issue":"10","key":"e_1_2_10_31_1","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202206144","article-title":"Reprogramming of Mitochondrial Respiratory Chain Complex by Targeting SIRT3\u2010COX4I2 Axis Attenuates Osteoarthritis Progression","volume":"10","author":"Zhang Y.","year":"2023","journal-title":"Adv Sci (Weinh)"},{"issue":"1","key":"e_1_2_10_32_1","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1038\/s41467-021-22829-2","article-title":"Oocyte\u2010Derived Microvilli Control Female Fertility by Optimizing Ovarian Follicle Selection in Mice","volume":"12","author":"Zhang Y.","year":"2021","journal-title":"Nature Communications"},{"issue":"16","key":"e_1_2_10_33_1","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.3390\/cells11162596","article-title":"The Role of SIRT3 in Exercise and 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