<i>Panax notoginseng</i> -Derived Carbon Dots Herbzymes Ameliorate Renal Ischemia-Reperfusion Injury via Anti-Inflammation, Antioxidation and Gut-Kidney Axis Regulation

Renal ischemia-reperfusion injury (RIRI) mainly comes from inflammation and oxidative stress. Treating with inflammation monotherapy or oxidative stress monotherapy can't reduce RIRI. This study involved the synthesis of <i>Panax notoginseng</i>-derived carbon dots (PN-CDs) herbzymes, nanozymes from Chinese herbal medicines, exhibiting inherent antioxidant enzymatic activity. The diverse surface functional groups facilitate the effective scavenging of reactive oxygen species (ROS) and suppress the expression of inflammatory factors. In the RIRI model, PN-CDs demonstrated extended systemic circulation and improved renal targeting, effectively decreasing renal tissue concentrations of neutrophil gelatinase-associated lipocalin (NGAL), creatinine, blood urea nitrogen, and kidney injury molecule-1 (KIM-1). They also decreased inflammatory factors and lipid peroxidation markers, thereby mitigating renal damage. Multi-omics analysis showed that PN-CD protects kidney function mainly via gut microbiota, shrinking nephrotoxins such as indoxyl sulfate and enhancing beneficial metabolisms such as β-indol-3-acetamide and stimulating pathways like aryl hydrocarbon receptor (AHR), ERK to reduce inflammation and oxidative stress. In conclusion, PN-CDs herbzyme was a potential treatment for RIRI and provided the theoretical basis for the herbzyme therapy of kidney disease, as well as the proof-of-concept for the gut-kidney axis.