AMPK/SIRT1/GPX4 signaling pathway mediates the protective effect of puerarin against LPS-induced endometritis in mice

Endometritis is a chronic inflammation characterized by plasma cell infiltration into the endometrial stroma, which can lead to adverse pregnancy outcomes such as infertility, recurrent miscarriages, and repeated embryo transfer failures. Puerarin (PR) is a flavonoid derivative that has anti-inflammatory and antibacterial effects. The aim of this study is to evaluate the effects of PR on LPS-induced endometritis and to elucidate its mechanism. The changes of inflammatory factors in endometrial tissue were detected by ELISA. Western-blot technology was used to analyze the expression of AMPK/SIRT1/GPX4 signaling at the protein level. It was found that PR markedly alleviated LPS-induced uterine pathological injury and the degree of inflammation. PR also inhibited LPS-induced ferroptosis in uterine tissues. In further mechanistic studies, the data showed that PR significantly inhibited LPS-induced NF-κB activation. Meanwhile, PR could up-regulate the expression of AMPK, SIRT1, and GPX4 decreased by LPS. In vitro, PR significantly inhibited LPS-induced TNF-α and IL-lβ expression in mouse endometrial epithelial cells (MEECs). The inhibition of PR on LPS-induced inflammatory response were reversed by AMPK inhibitor compound C and SIRT1 inhibitor EX-527. In conclusion, the data demonstrated that PR exhibited therapeutic effects against LPS-induced endometritis through attenuating ferroptosis and inflammatory response.