Cangfu Daotan decoction treats PCOS-IR through the IL6/JAK2/STAT3/FOXO4 signaling pathway

Wenhan Ju¹Qianwen Zhang²Yue Wang²Keying Pan²Yuan Li³Shuai Zhao²Fang Lian^3*

• ¹Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
• ²Shandong University of Traditional Chinese Medicine, Jinan, China
• ³Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, China

Objective: This study aimed to investigate the protective effects and underlying mechanisms of Cangfu Daotan Decoction (CDD) in both vivo and in vitro models of polycystic ovary syndrome with insulin resistance (PCOS-IR) . Materials and methods: Active compounds in CDD were identified using UPLC-HRMS. Network pharmacology and molecular docking analyses were employed to predict key molecular targets. A PCOS-IR mouse model was established through administration of letrozole and a high-fat diet. In vitro, KGN cells were used to simulate granulosa cell dysfunction associated with PCOS-IR. The regulatory effects of CDD on the IL6/JAK2/STAT3/FOXO4 signaling pathway were further evaluated. Results: Fifteen active compounds in CDD were preliminarily identified. Ninety-four potential target genes related to the treatment of PCOS-IR were screened. Network pharmacology and molecular docking analyses indicated strong binding affinities between STAT3 and several active compounds of CDD. CDD improved ovarian function and reduced insulin resistance in PCOS model mice. In vitro, CDD also enhanced glucose intake in granulosa cells under PCOS-IR conditions. Both in vivo and in vitro experiments demonstrated that CDD significantly suppressed activation of the IL6/JAK2/STAT3/FOXO4 signaling pathway. Conclusion: CDD may improve ovarian function and insulin resistance in PCOS-IR mice by modulating the IL6/JAK2/STAT3/FOXO4 signaling pathway.