Flavonoids from Smilax china L. Rhizome improve chronic pelvic inflammatory disease by promoting macrophage reprogramming via the NLRP3 inflammasome-autophagy pathway

Smilax is a traditional medicine used for the clinical treatment of pelvic inflammatory disease (CPID), and its leaves have long been used as food by the Korean people in Asia. In previous studies, we found that flavonoids extract can improve CPID by inhibiting inflammation, which may be the main effective component of Smilax China, but its mechanism of action has not been fully elucidated. This study explores the mechanism by which Chinese rhizome flavonoids (FSCR) regulate the autophagy pathway of NLRP3 inflammasome and promote macrophage reprogramming. In the in vivo experiment, the sham surgery group and the CPID group were given physiological saline and FCSR for 7 days, respectively. We determined the expression of NLRP3 inflammasome autophagy pathway genes and proteins by observing the pathological damage of rat uteri through HE and Masson staining, immunofluorescence, RT-PCR, and WB experiments. Molecular docking simulation predicted the binding potential of flavonoids with the potential target VPS34, and knockdown experiments were conducted to validate the knockdown effect of lipopolysaccharide treatment on primary rat endometrial cells to simulate an in vitro CPID model. FCSR significantly reduced serum IL-1β in CPID rats, TNF-α. The concentration of TAX2 reduced the infiltration of inflammatory cells and fibrosis of endometrial cells, promoted M2 polarization of macrophages, upregulated autophagy pathways, and inhibited the activation of NLRP3 inflammasomes. After knocking down the NLRP3 inflammasome autophagy target VPS34, the FSCR effect was eliminated. By targeting VPS34, FCSR potentially promotes autophagic cell reprogramming through the NLRP3 inflammasome related autophagy pathway.