Total glucosides of Paeony alleviates chronic endometritis in rats through regulating gut microbiota composition and inhibiting TLR4/NF-κB/NLRP3 pathway

Objective This study aimed to elucidate the functional role and regulating mechanism of Total Glucosides of Paeony (TGP) in chronic endometritis (CE). Methods To assess the impact of TGP on CE, a CE rat model was established via infusion with 60 µL of 5.0 mg/mL LPS, while human endometrial stromal cells (HESCs) were pre-treated with 500 ng/mL LPS to simulate a CE cell model. Cell proliferation and apoptosis were evaluated using CCK-8, Flow cytometry and EDU staining techniques. Histological changes in uterine tissues were evaluated using H&E staining, while NLRP3 expression was analyzed via IHC staining. Levels of TNF-α, IL-1β, IL-6, and IL-10 in tissues were determined using enzyme-linked immunosorbent assay (ELISA). Additionally, the impact of TGP on intestinal flora was investigated using 16S rRNA sequencing. Results TGP treatment attenuated pathological changes in uterine structure and inflammatory response in CE rats. It effectively suppressed the activation of the TLR4/NF-κB/NLRP3 pathway in CE rats. Moreover, TGP significantly enhanced the diversity and richness of intestinal microbiota in CE rats. The CE cell model further validated that TGP suppressed inflammation in LPS-induced HESCs. Conclusion TGP demonstrates beneficial effects on LPS-induced chronic endometritis in rats through modulating the composition of intestinal microbiota and inhibition of TLR4/NF-κB/NLRP3 pathway.