Crocins ameliorate acute kidney injury in glycerol-induced rhabdomyolysis by targeting the PLIN1/PPARs signaling pathway

Background Rhabdomyolysis (RM) is a potentially life-threatening syndrome characterized by skeletal muscle damage, with acute kidney injury (AKI) being its most severe complication. Currently, no effective treatment exists for RM-induced AKI. Crocins, the major bioactive constituents extracted from the stigma of Crocus sativus L. (Saffron), possess diverse pharmacological activities. Objectives This study aimed to explore the pharmacological effect and possible mechanism of crocins in the treatment of RM-induced AKI. Method Network analysis was first applied to predict potential targets of crocins against RM. A rat model of hypertonic glycerol-induced RM was then established to evaluate pharmacological effect, including assessment of muscle and renal pathology, inflammatory cytokines, biochemical markers, and oxidative stress-related enzymes. Tandem mass tag–based quantitative proteomics was further employed to identify key disease targets. Molecular docking was then conducted to validate potential target interactions of crocins in RM-induced AKI treatment. Results Animal experiments demonstrated that crocins alleviated muscle and renal injuries by inhibiting inflammation and oxidative stress while preserving hepatic and renal functions. Proteomic analysis identified perilipin 1 (PLIN1) as a critical candidate biomarker mediating these effects. Both network analysis and proteomics indicated that the peroxisome proliferator-activated receptors (PPARs) signaling pathway was closely involved in protective mechanism. Furthermore, Western blotting confirmed that crocins exerted pharmacological effect through regulating the PLIN1/PPARs signaling pathway. Molecular docking revealed that the best docking activities were demonstrated by crocin I/II–PLIN1, crocin I–PPARα, and crocin II–PPARγ. Conclusion Crocins mitigated RM-induced AKI primarily by suppressing inflammation and oxidative stress via the PLIN1/PPARs signaling pathway. These findings provide a scientific and theoretical basis for the potential clinical application of crocins in treating RM-induced AKI.