Treatment of Qin Gui Wan (QGW) in PCOS abnormal oocytes development via AMPK/PGC-1ɑ pathway.

OBJECTIVES

To investigate the therapeutic effects of Qin Gui Wan (QGW) and its disassembled functional drug groups, Wenyang Zhuhuo (WYZH) and Xinwen Zhuyang (XWZY), on letrozole-induced PCOS rats.

METHODS

PCOS rat model was established by administering letrozole for 21 days. The rats were divided into control, PCOS, Diane-35, QGW, WYZH and XWZY groups. The changes of body weight, ovarian coefficient, estrous cycle and sex hormone levels were observed. The ovarian histological characteristics and ovulation were observed by HE staining. P450arom, SF-1, and AMPK/PGC-1ɑ pathway mRNA and protein expression were analyzed using qRT-PCR, WB, and IHC. The AMPK inhibitor Compound C (CC) was used to explore the treatment mechanism of QGW in granulosa cells. And UHPLC-MS/MS was used to performed chemical composition analysis.

RESULTS

QGW, WYZH, and XWZY can correct the disordered estrous cycle of PCOS rats and improve the serum hormone status of rats to varying degrees. HE results indicated that QGW, WYZH, and XWZY improved ovarian polycystic changes and normalized ovulation. qRT-PCR, WB, and IHC results demonstrated that QGW, WYZH, and XWZY increased PGC-1α, SF-1, and P450arom mRNA and protein expression in the ovaries of PCOS rats. The level of AMPK mRNA in the ovaries of QGW and its disassembled prescriptions increased, while only WYZH and XWZY rats showed increased ovarian AMPK levels. CC attenuated the activation of AMPK, PGC-1α, SF-1, and P450arom mRNA by QGW.

CONCLUSIONS

This study demonstrates that QGW alleviates abnormal oocyte development in PCOS rats, possibly by enhancing P450arom expression via the AMPK/PGC-1α pathway, thus restoring normal androgen-estrogen balance and follicular development.