Lin Yi, Zhang Yahui, Ding Xiaoying, Xu Huanbai, Xiong Chuanhao, Tang Min, Peng Yongde
Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
Eur J Pharmacol. 2025 Sep 5;1002:177870. doi: 10.1016/j.ejphar.2025.177870. Epub 2025 Jun 20.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder, and the effects of chlorogenic acid (CA) on it are unclear. This study investigated CA's therapeutic effects and mechanisms on a dehydroepiandrosterone (DHEA)-induced PCOS rat model and KGN granulosa cells, hypothesizing that CA ameliorates hormonal imbalance, inflammation, and oxidative stress in PCOS by regulating the NF - κB signaling pathway and ferroptosis - related proteins. The methods included in - vivo experiments on rats with different treatments and in - vitro experiments on KGN cells. Results showed that CA restored the estrous cycle and ovulation, alleviated hyperandrogenism, reduced inflammation and oxidative stress markers, improved follicular development, and decreased ferroptosis in PCOS rats. It upregulated GPX4 and SLC7A11 expression, decreased ROS levels, and bound strongly with NF - κB p65, downregulating NF - κB pathway activation markers. In KGN cells, CA improved proliferation, reduced ferroptosis, oxidative stress, and mitochondrial damage, similar to Fer - 1. The combined use of an NF - κB inhibitor and CA restored the cellular oxidative state. In conclusion, CA improves hormonal balance, alleviates inflammation and oxidative stress by regulating the NF - κB pathway and ferroptosis - related proteins, showing potential as a PCOS therapeutic agent, and further studies are needed for confirmation and clinical application exploration.
多囊卵巢综合征（PCOS）是一种常见的内分泌紊乱疾病，而绿原酸（CA）对其影响尚不清楚。本研究调查了CA对脱氢表雄酮（DHEA）诱导的PCOS大鼠模型和KGN颗粒细胞的治疗作用及机制，推测CA通过调节NF-κB信号通路和铁死亡相关蛋白来改善PCOS中的激素失衡、炎症和氧化应激。方法包括对大鼠进行不同处理的体内实验以及对KGN细胞进行的体外实验。结果显示，CA恢复了PCOS大鼠的发情周期和排卵，减轻了高雄激素血症，降低了炎症和氧化应激标志物，改善了卵泡发育，并减少了铁死亡。它上调了GPX4和SLC7A11的表达，降低了ROS水平，并与NF-κB p65强烈结合，下调了NF-κB通路激活标志物。在KGN细胞中，CA改善了细胞增殖，减少了铁死亡、氧化应激和线粒体损伤，类似于Fer-1。联合使用NF-κB抑制剂和CA恢复了细胞的氧化状态。总之，CA通过调节NF-κB通路和铁死亡相关蛋白改善了激素平衡，减轻了炎症和氧化应激，显示出作为PCOS治疗药物的潜力，尚需进一步研究以证实并探索其临床应用。
