Water-soluble polysaccharides derived from Poria cocos protect against LPS-induced renal injury through inhibiting the NF-κB-NOX4 signaling pathway

Sepsis frequently results in acute kidney injury (AKI), characterized by oxidative damage and inflammation. Polysaccharides derived from Poria cocos have significant anti-inflammatory and antioxidant effects. This study aims to investigate the role of water-soluble Poria cocos polysaccharide (WPCP) in sepsis-related renal damage by administering lipopolysaccharide (LPS) in mice. WPCP significantly reduced serum levels of BUN, creatinine, NGAL, and KIM-1, as well as renal tubular tissue damage in LPS-treated mice. WPCP was effective in reducing both the serum levels and the expression of inflammatory factors (IL-1β, IL-6, MCP-1, and TNF-α) in kidney tissue. Moreover, WPCP blocked the increase in ROS levels and caspase-3/7 activity induced by LPS, while also preventing the decrease in GSH and ATP levels. The results were also confirmed by in vitro experiments. Mechanistically, WPCP significantly suppressed LPS-induced NOX4 expression and NADPH oxidase activation. Alternatively, studies demonstrated WPCP inhibited the activation of NF-κB by preventing the phosphorylation of IκBα caused by LPS. Importantly, our findings confirmed that the activation of NF-κB signaling by LPS is involved in NADPH oxidase activation. These data suggest that WPCP mitigates LPS-induced AKI through the suppression of the NF-κB-NOX4 signaling pathway. WPCP could be a potential therapeutic option for treating sepsis-related AKI.