Panax notoginseng Saponins Alleviate OSF by Inhibiting Ferroptosis Through GPX4 Activation

OBJECTIVES: Oral submucous fibrosis (OSF) is a chronic progressive disease characterized by fibrosis. Panax notoginseng saponins (PNS) are effective components of the traditional Chinese medicine Panax notoginseng and play an important role in the treatment of OSF. However, the underlying mechanism of action for this medicine remains unclear. The aim of this study was to explore the effects of ferroptosis in OSF. SUBJECTS AND METHODS: The mice were divided into six groups. Mouth openings were detected. The buccal tissues were harvested for histomorphological analysis, western blot, and RT-qPCR. The cells were harvested for CCK8 detection, western blot, RT-qPCR, TEM, immunofluorescence, fluorescent probe, and colorimetry. RESULTS: PNS improved mouth opening, alleviated tissue cell damage, and inhibited ferroptosis and fibrosis in OSF rat models. Our study found that ferroptosis is closely related to arecoline-induced OSF and that PNS inhibits ferroptosis by upregulating glutathione peroxidase 4 (GPX4) to alleviate OSF. CONCLUSIONS: The research established OSF in vivo and in vitro, respectively, and the changes in the expression of fibrosis and ferroptosis-related markers in these models were studied to provide a theoretical and experimental basis for the clinical prevention and treatment of OSF.