<i>Poria cocos</i> Polysaccharides Protect Against Contrast‐Induced Renal Injury Through Activating <scp>CaMKK2</scp> / <scp>AMPK</scp> / <scp>PGC</scp> ‐1α Signaling Pathway

The necessity of iodinated contrast agents in radiographic diagnosis comes with an increased risk of kidney injury. The sclerotium of Poria cocos (Schw.) Wolf, a traditional Chinese medicine, exhibits anti-inflammatory and diuretic pharmacological properties. Its extracted polysaccharides demonstrate anti-apoptotic, antioxidant, and anti-inflammatory activities. This study aimed to investigate the effects and potential mechanisms of Poria cocos polysaccharides (PCP) on contrast-induced acute kidney injury (CI-AKI). The purified PCP was characterized using FTIR and monosaccharide analysis. A CI-AKI mouse model was established to evaluate its preventive effects via oral gavage. Mitochondrial structure, function, and biogenesis were assessed by measuring mitochondrial membrane potential (MMP), ROS, ATP, and mitochondrial DNA copy number. Antioxidant capacity and apoptosis levels were evaluated by detecting 8-OHdG, caspase 3/7 activity, cleaved-PARP, MDA, and GSH. Finally, the mechanism of action of PCP was analyzed using qPCR and immunoblotting. The results showed that PCP significantly mitigated CI-AKI by inhibiting contrast-induced apoptosis and oxidative stress in kidney tissue. Furthermore, PCP maintained mitochondrial homeostasis in the kidneys by enhancing mitochondrial biogenesis and antioxidant capacity. These findings were consistent with in vitro data. Notably, PGC-1α was identified as a key factor in the nephroprotective effects of PCP, with its activation attributed to the CaMKK2-AMPK signaling pathway. These findings suggest that PCP offers significant benefits in mitigating CI-AKI by enhancing antioxidant defenses and promoting mitochondrial biogenesis through activation of the CaMKK2/AMPK/PGC-1α signaling pathway in the kidney. Therefore, PCP could be a potential preventive agent for CI-AKI.