Dried Zingiber officinale Alleviates Dehydroepiandrosterone-Induced Ovarian Granulosa Cell Apoptosis via the Reactive Oxygen Species-Mediated Pathway

Abstract

Polycystic ovary syndrome (PCOS), a prevalent reproductive endocrine disorder, frequently coincides with insulin resistance, lipid dysregulation, and cellular apoptosis. In this study, we aimed to evaluate the therapeutic potential of Dried Zingiber officinale (DZO), renowned for its antibacterial, antiviral, anti-inflammatory, and antioxidant properties, in the context of PCOS. To this end, we induced a PCOS mouse model through the administration of dehydroepiandrosterone (DHEA) and a high-fat diet (HFD), followed by DZO treatment to assess its effects on ovarian pathology, insulin resistance, and hormonal imbalances. The anti-apoptotic effect of DZO on PCOS ovarian granulosa cells was confirmed through network pharmacological analysis, TUNEL staining, FITC-PI staining, and protein blotting. Notably, DZO treatment significantly alleviated ovarian pathological changes in PCOS mice and normalized hormone levels, including testosterone, estradiol, and progesterone/follicle-stimulating hormone ratios. Furthermore, our findings confirmed the anti-apoptotic effect of DZO on PCOS ovarian granulosa cells. Mechanistically, DZO primarily exerted its therapeutic effects in PCOS by inhibiting apoptosis induced by the accumulation of reactive oxygen species (ROS). In conclusion, our study demonstrates the promising therapeutic role of DZO in the management of obese PCOS patients, particularly in reversing ROS-mediated apoptosis in ovarian granulosa cells.