Vitexin Reduced the Dihydrotestosterone (DHT)-Induced Fibrosis in KGN Cells by Regulating the NR4A1/NLRP3 Pathway

Abstract

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder in women of reproductive age, markedly impairing their health and reducing overall quality of life. Vitexin is a natural flavonoid compound that has demonstrated diverse pharmacological properties, including anti-inflammatory and antioxidant effects. The aim of this study was to investigate the effects of vitexin on dihydrotestosterone (DHT)-induced fibrosis in KGN cells, as well as its regulatory role in the NR4A1/NLRP3 signaling pathway. Experimental findings suggested that DHT treatment resulted in decreased cell viability, disrupted sex hormone balance, increased oxidative stress, and elevated levels of inflammation and fibrosis in KGN cells. However, vitexin intervention significantly reversed these pathological changes. Transcriptomics sequencing analysis and molecular docking further indicated that NR4A1 is a pivotal target of vitexin in modulating the inflammatory response. Vitexin significantly inhibited NLRP3 inflammasome-mediated inflammation by activating NR4A1, conversely NR4A1 knockdown partially attenuated the protective effects of vitexin (P < 0.01). Therefore, vitexin was found to effectively ameliorate DHT-induced alterations in cell viability, sex hormone levels, oxidative stress, inflammation and fibrosis in KGN cells. These protective effects appear to be closely related to the regulation of the NR4A1/NLRP3 signaling pathway.

Keywords: NR4A1/NLRP3 signaling pathway; Polycystic ovary syndrome; fibrosis; inflammation; vitexin.