She ethnomedicine ameliorates ovarian dysfunction through enhanced cellular proliferation and anti-inflammation

Polycystic ovary syndrome (PCOS) and premature ovarian failure (POF) are common causes of female infertility, both characterized by endocrine and metabolic dysregulation and anovulation. The She ethnomedicine formula, Medical Research Center Sheyao No. 1 (MRCSY1#), traditionally used for reproductive disorders, remains mechanistically underexplored.

To explore pharmacological mechanisms underlying the effects of MRCSY1# in treating ovarian dysfunction-related infertility.

The active compounds in MRCSY1# were identified using ultra-high-performance l‌iquid c‌hromatography-q‌uadrupole Exactive Orbitrap high-field high-resolution mass spectrometry‌ (UHPLC-Q HF-HRMS). Network pharmacology analysis was used to identify key genes and potential pathways. The therapeutic effects of MRCSY1# were evaluated in mouse models of dehydroepiandrosterone-induced PCOS and cyclophosphamide-induced POF. The assessments included histopathological analysis, hormone profiling, oxidative stress measurement, and fertility evaluation.

Phytochemical analyses identified 153 bioactive components in MRCSY1#. Among these, several bioactive compounds, including protocatechuic acid, gallic acid, nobiletin, and vanillic acid, were found to mitigate ovarian oxidative stress by modulating the PI3K-Akt/MAPK signaling pathway. MRCSY1# treatment enhanced the frequency of estrus and increased litter size. Furthermore, this formulation alleviated chronic inflammation and restored hormonal balance in PCOS mice. Specific components also activated immune responses, counteracting oocyte maturation arrest in the POF model. Overall, She ethnomedicine improved ovulatory function, promoted uterine endometrial vascular regeneration, and restored fertility in the experimental mice.

MRCSY1# exhibits a multifaceted therapeutic effect against female infertility, primarily through the coordinated inhibition of ovarian inflammation, oxidative stress, and granulosa cell apoptosis. These findings provide mechanistic support for the development of standardized botanical therapies based on traditional She ethnomedicine.