Huang Xiaohan, Geng Hucheng, Liang Chunxiao, Xiong Xianglei, Du Xingzhu, Zhuan Qingrui, Liu Zhiqiang, Meng Lin, Zhou Dan, Zhang Luyao, Fu Xiangwei, Qi Xinyu, Hou Yunpeng
State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
Free Radic Biol Med. 2025 Jan;226:330-347. doi: 10.1016/j.freeradbiomed.2024.11.021. Epub 2024 Nov 14.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder marked by ovarian dysfunction and metabolic abnormality. This study explores the therapeutic potential of leonurine (SCM-198) in PCOS. Our results show that SCM-198 treatment significantly improved ovarian function, hormone disorders and insulin resistance while reducing granulosa cell ferroptosis. This study provides the first evidence that SCM-198 modulates the gut microbiota composition, increases the abundance of Christensenella minuta, and boosts butyrate levels. Transcriptomic and metabolomic analyses revealed that PCOS patients exhibit granulosa cell ferroptosis and decreased butyrate levels in follicular fluid. Butyrate was shown to alleviate ferroptosis in granulosa cells via the SLC7A11/TXNRD1/GPX4 pathway, as confirmed in vitro with KGN cells. The therapeutic mechanism of SCM-198 in the management of PCOS via the gut microbiota-ovary axis involves the enhancement of gut microbiota and its metabolites. This intervention improves ovarian function and alleviates PCOS symptoms by targeting ferroptosis in granulosa cells.
多囊卵巢综合征（PCOS）是一种常见的内分泌紊乱疾病，其特征为卵巢功能障碍和代谢异常。本研究探讨了益母草碱（SCM-198）对PCOS的治疗潜力。我们的结果表明，SCM-198治疗显著改善了卵巢功能、激素紊乱和胰岛素抵抗，同时减少了颗粒细胞铁死亡。本研究首次证明SCM-198可调节肠道微生物群组成，增加微小克里斯滕森菌的丰度，并提高丁酸盐水平。转录组学和代谢组学分析显示，PCOS患者的颗粒细胞存在铁死亡，且卵泡液中丁酸盐水平降低。体外实验在KGN细胞中证实，丁酸盐可通过SLC7A11/TXNRD1/GPX4途径减轻颗粒细胞的铁死亡。SCM-198通过肠道微生物群-卵巢轴治疗PCOS的机制涉及增强肠道微生物群及其代谢产物。这种干预通过靶向颗粒细胞的铁死亡来改善卵巢功能并减轻PCOS症状。
