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Bibliographic Details
Main Authors: Zhang, Shilin, Xu, Yan, Zhang, Jingxi, Liang, Qingsheng, Chen, Zhengdao, Zhang, Mengyue, Sun, Jingyu, Chen, Shaohong, Hu, Chuanyin, Zhao, Yun-Tao
Format: Artículo científico
Language:en
Published: International journal of molecular sciences 2026
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Online Access:https://pubmed.ncbi.nlm.nih.gov/42278374/
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Table of Contents:
  • Hydroxytyrosol Enhances the Nrf2/HO-1 Signalling Pathway to Inhibit Oxidative Stress and Apoptosis and Improve Premature Ovarian Insufficiency In Vitro and In Vivo. Zhang, Shilin Xu, Yan Zhang, Jingxi Liang, Qingsheng Chen, Zhengdao Zhang, Mengyue Sun, Jingyu Chen, Shaohong Hu, Chuanyin Zhao, Yun-Tao Female Phenylethyl Alcohol Animals NF-E2-Related Factor 2 Oxidative Stress Apoptosis Humans Primary Ovarian Insufficiency Signal Transduction Heme Oxygenase-1 Mice Reactive Oxygen Species Granulosa Cells Cell Line, Tumor Premature ovarian insufficiency (POI) poses a serious risk to the reproductive health and psychological well-being of women. Here, the protective effects of hydroxytyrosol (HT), the primary phenolic component of olive oil, on POI were investigated. In vitro, human ovarian granulosa-like tumour cell lines (KGN cells) were challenged by D-galactose (D-gal) with or without HT. HT administration effectively alleviated KGN cell damage, decreased the number of senescence-associated β-galactosidase (SA-β-gal)-positive cells, increased superoxide dismutase (SOD) activity, reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, enhanced the expression level of Bcl-2, inhibited the expression level of Bax, and inhibited cell apoptosis in D-gal-treated KGN cells. In vivo, HT administration reversed the decreased ovarian index, oestrous cycle disruption, and abnormal sex hormone levels observed in D-gal-induced POI mice. HT administration increased glutathione (GSH) levels, reduced the MDA levels, and attenuated apoptosis in ovarian tissues, as evidenced by a decreased number of TUNEL-positive cells, upregulated Bcl-2 expression, and downregulated Bax expression. Mechanistically, HT downregulated the expression level of Kelch-like ECH-associated protein 1 (Keap1) and enhanced the expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in vitro and in vivo. In conclusion, HT ameliorates D-gal-induced POI in vitro and in vivo by activating the Nrf2/HO-1 signalling pathway.