Multi-omics strategy reveals that Cordyceps sinensis ameliorates sepsis-associated acute kidney injury via reprogramming of mitochondrial energy metabolism and macrophage polarization

Cordyceps sinensis (CS) has been widely used as a dietary supplement or traditional medicine for the prevention, treatment, and prognostication of various diseases, because of its pleiotropic pharmacological properties. However, the potential pharmacological action of CS in sepsis-associated acute kidney injury (S-AKI) remains poorly understood. Herein, we investigated the potential pharmacological action of CS against S-AKI and the underlying mechanisms. CS treatment effectively ameliorated renal dysfunction and injury in mice with lipopolysaccharide (LPS)-induced S-AKI, as indicated by the suppression of inflammatory cytokine expression and secretion. Multi-omic analyses suggested that the promotion of mitochondrial energy metabolism might be a potential mechanism through which CS protects mice against S-AKI induced by LPS. Subsequent validation assays confirmed that CS treatment substantially restored the activity of mitochondrial complexes, mitochondrial membrane potential, and ATP production. Moreover, CS concomitantly promoted transition of M1 macrophages to M2 macrophages with increased oxidative phosphorylation, thus indicating that macrophage polarization may also be a potential target for S-AKI treatment. Our findings demonstrated that CS significantly ameliorated renal injury and inflammation in S-AKI by regulating mitochondrial energy metabolism and macrophage polarization, thus providing new insights into the clinical use of CS for the prevention and treatment of S-AKI.