The effect of isovitexin on lipopolysaccharide-induced renal injury and inflammation by induction of protective autophagy

Abstract

Chronic kidney disease (CKD) is a systemic inflammatory syndrome that includes tubulointerstitial inflammation. Lipopolysaccharide (LPS), the outer membrane of Gram-negative bacteria, can increase reactive oxygen species production (ROS) that triggers cell inflammation. Isovitexin (IV) is a flavone that has the potential for anticancer, antioxidant, and anti-inflammatory. This study aimed to hypothesize that IV inhibited LPS-induced renal injury in vitro and in vivo. In vitro study, IV prevented LPS-induced ROS production and increased cell viability on SV40-MES-13 cells. Additionally, IV ameliorated mitochondrial membrane potential, downregulated inflammation and pyroptosis factors on LPS treatment. We found that LPS treatment reduced the expression of autophagy, however, this effect was reversed by IV. In vivo study, the renal injury model in C57BL/6 mice cotreatment with IV was examined. In addition, IV decreased LPS-induced glomerular atrophy and reduced inflammation-related cytokines releases. Further showed that IV could significantly reduce LPS-induced inflammation and pyroptosis factors in mice. Under the immunostaining, increased fluorescence of LC3 autophagy-related protein was recovered by IV. In summary, IV ameliorated renal injury, inflammation and increased protected autophagy by anti-ROS production, anti-inflammation, and anti-pyroptosis. In the future, the safety of isovitexin as a novel perspective for CKD patients should be evaluated in further clinical studies.

Keywords: Autophagy; Inflammation; Isovitexin; Kidney injury; Lipopolysaccharide.