Polygonum cuspidatum Sieb. et Zucc. Extracts improve sepsis-associated acute kidney injury by inhibiting NF-κB-mediated inflammation and pyroptosis

Polygonum cuspidatum Sieb. et Zucc. (Polygonum cuspidatum) is a herbaceous perennial plant in the Polygonaceae family that produces biofunctional stilbenes and quinones. The dried rhizome and root of P. cuspidatum in traditional oriental medicine have been used for ameliorating inflammatory illnesses, diabetes, gout, cancer, and other ailments.This work aimed to investigate the protective effects of P. cuspidatum extracts (PCE) on sepsis-associated acute kidney injury (SA-AKI) and its underlying mechanism.The potential mechanisms by which PCE improved SA-AKI were preliminarily predicted by network pharmacology. The dry powders of PCE were obtained using the freeze-drying method. A mouse model of SA-AKI was established by intraperitoneal injection of lipopolysaccharide (LPS). The protective effects of PCE on SA-AKI in vivo were studied using pathological and biochemical methods. LPS-stimulated HK-2 cells were prepared for in vitro evaluation. The qPCR and immunoblotting assays were performed to confirm the mechanism involved.The network pharmacology results indicate that emodin (Emo) and polydatin (PD) are potential active components of P. cuspidatum ameliorating SA-AKI. The experimental results showed that PCE improved renal function indices (creatinine, urea nitrogen, and urinary protein) in SA-AKI mice. Mechanistically, PCE mitigated oxidative stress, regulated the expression levels of pyroptosis-related proteins, and repressed the production of inflammatory cytokines by inactivating nuclear factor-kappa B (NF-κB) signaling in vivo. Similar results were observed in LPS-stimulated HK-2 cells in the presence of Emo or PD.Our results demonstrated that PCE and active ingredients (Emo and PD) in PCE ameliorated SA-AKI by suppressing oxidative stress, inflammation, and pyroptosis.