1. Leonurine restrains granulosa cell ferroptosis through SLC7A11/GPX4 axis to promote the treatment of polycystic ovary syndrome.
- Author
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Huang, Xiaohan, Geng, Hucheng, Liang, Chunxiao, Xiong, Xianglei, Du, Xingzhu, Zhuan, Qingrui, Liu, Zhiqiang, Meng, Lin, Zhou, Dan, Zhang, Luyao, Fu, Xiangwei, Qi, Xinyu, and Hou, Yunpeng
- Subjects
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GRANULOSA cells , *POLYCYSTIC ovary syndrome , *BUTYRIC acid , *ENDOCRINE diseases , *INSULIN resistance , *BUTYRATES - Abstract
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. [Display omitted] • SCM-198 alleviates ovarian dysfunction and insulin resistance in PCOS-like mice. • Christensenella minuta and butyric acid are key contributors to the treatment of PCOS. • Butyrate inhibits ferroptosis in granulosa cells through the SLC7A11/GPX4 pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2025
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