Chlorogenic acid mitigates DHEA-induced oxidative stress in granulosa cells and alleviates ferroptosis via the NF-κB signaling pathway in PCOS

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, and the effects of chlorogenic acid (CA) on it are unclear. This study investigated CA's therapeutic effects and mechanisms on a dehydroepiandrosterone (DHEA)-induced PCOS rat model and KGN granulosa cells, hypothesizing that CA ameliorates hormonal imbalance, inflammation, and oxidative stress in PCOS by regulating the NF - κB signaling pathway and ferroptosis - related proteins. The methods included in - vivo experiments on rats with different treatments and in - vitro experiments on KGN cells. Results showed that CA restored the estrous cycle and ovulation, alleviated hyperandrogenism, reduced inflammation and oxidative stress markers, improved follicular development, and decreased ferroptosis in PCOS rats. It upregulated GPX4 and SLC7A11 expression, decreased ROS levels, and bound strongly with NF - κB p65, downregulating NF - κB pathway activation markers. In KGN cells, CA improved proliferation, reduced ferroptosis, oxidative stress, and mitochondrial damage, similar to Fer - 1. The combined use of an NF - κB inhibitor and CA restored the cellular oxidative state. In conclusion, CA improves hormonal balance, alleviates inflammation and oxidative stress by regulating the NF - κB pathway and ferroptosis - related proteins, showing potential as a PCOS therapeutic agent, and further studies are needed for confirmation and clinical application exploration.

Keywords: Chlorogenic acid; Ferroptosis; Inflammation; NF-κB pathway; Polycystic ovary syndrome.