Sedum sarmentosum Bunge extract alleviates inflammation and kidney injury via inhibition of M1-macrophage polarization

Sedum sarmentosum Bunge extract (SSBE) has been used traditionally to treat liver inflammatory diseases in the Asian area. The aim of this study is to evaluate the anti-inflammatory activity of SSBE on renal injury. We investigated whether SSBE has an anti-inflammatory effect by suppressing M1-macrophage polarization in rats with unilateral ureteral obstruction (UUO) and in cultured macrophages. In addition, the effect of SSBE on the activities of interferon regulatory factor-5 (IRF5) and NF-κB p65 were further examined. Oral administration of SSBE (100 mg kg−1) markedly inhibited the infiltration of CD68-positive macrophages and reduced tubulointerstitial damage in kidney tissues following injury. In addition, SSBE reduced the expression of proinflammatory cytokine (MIF), chemokine (MCP-1), interleukin (IL-6), IFN-γ, and TNF-α, which are involved in the infiltration and activation of macrophages. Moreover, SSBE treatment also decreased the synthesis and release of MCP-1 and MIF in tubular epithelial cells after injury. Further study revealed that SSBE downregulated the levels of IL-12 and iNOS, indicating a crucial role of SSBE on the inhibition of M1 macrophage polarization in kidney injury. In cultured macrophages, lipopolysaccharide (LPS) induced the polarization of macrophage towards M1 phenotype, but was inhibited by SSBE treatment. Notably, SSBE reduced the activities of interferon regulatory factor 5 (IRF5) and NF-κB p65 in injured kidneys and in LPS-treated macrophages, which was independent of TLR4/MyD88. As a result, SSBE reduced the expression of HIF-1α and the induction of GLUT1, and thereby inhibited anaerobic glycolysis in macrophages. SSBE exerts a marked anti-inflammatory effect and alleviates kidney injury, at least in part, by suppressing M1-macrophage polarization.