Berberine Attenuates Pyroptosis in Renal Tubular Epithelial Cells by Activating the FOXO3a/ARC Pathway

ABSTRACT Renal ischemia/reperfusion (I/R) injury is primarily mediated by oxidative stress, inflammation, and pyroptosis. Berberine (BBR), a naturally occurring isoquinoline alkaloid, possesses anti‐inflammatory, antipyroptotic, and antioxidant properties. However, the impact of BBR on renal I/R injury remains unclear. This study aimed to investigate the effects of BBR on renal I/R injury using an in vitro model. An in vitro hypoxia/reoxygenation (H/R) model was employed to evaluate the effects and underlying mechanisms of BBR. Cellular viability, oxidative stress, and inflammatory cytokine levels were assessed using commercial kits and ELISA, whereas Western blotting was used to evaluate pyroptosis‐related proteins and to explore the molecular mechanism. The results demonstrated that BBR improved the viability of human renal tubular epithelial cells (HK‐2) subjected to H/R. BBR treatment significantly reduced oxidative stress and the production of inflammatory cytokines in HK‐2 cells. Furthermore, the extent of pyroptosis was markedly decreased in the BBR‐treated group compared to the H/R group. Mechanistically, BBR upregulated the expression of phosphorylated FOXO3a (p‐FOXO3a) and ARC in HK‐2 cells. These findings suggest that BBR protects HK‐2 cells against H/R‐induced injury, and this protective effect may be mediated through activation of the FOXO3a/ARC signaling pathway.