Carboxymethyl Poria cocos polysaccharides protect against septic kidney injury by regulating the Nrf2-NF-κB signaling pathway

Sepsis is one of the most common causes of acute kidney injury (AKI). Oxidative stress and inflammation within renal tissues are critical pathogenic mechanisms of septic AKI (S-AKI). Carboxymethylated Poria cocos polysaccharides (CMP) exhibit significant anti-inflammatory and antioxidant properties. This study aims to examine the effects of CMP on S-AKI model in vivo and in vitro. Oral administration of CMP significantly reduced renal injury induced by lipopolysaccharide (LPS) and cecal ligation and puncture (CLP). CMP not only effectively reduced the levels of inflammatory factors in both peripheral and renal tissues, including TNF-α, IL-6, IL-1β, and MCP-1, but also enhanced the expression of antioxidant genes in renal tissues, such as NQO1, HO-1, SLC7A11, and GPX4. Additionally, in vitro studies confirmed that CMP protects HK-2 cells from LPS-induced injury. Mechanistically, Nrf2 was identified as the primary regulator of CMP in exerting its protective effects on renal function. CMP activates the expression of antioxidant genes by stimulating Nrf2, while simultaneously inhibiting the activation of NF-κB signaling by blocking the phosphorylation of IκBα. In conclusion, CMP has potential applications in the prevention and mitigation of S-AKI in clinical practice.