Carbon Dots Derived from Ligusticum chuanxiong Alleviate Acute Kidney Injury by Scavenging ROS and Restoring Mitochondrial Homeostasis

Sen Liu,1,* Siyao Sun,1,2,* Hang Li,3 Hongli Zhou,1 Xiangfei Cui,1 Shiyan Ruan,1 Yong Liu,1 Yao Tong,4 Miaomiao Lu1 1Department of Nephrology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, People’s Republic of China; 2Department of Critical Care Medicine, Huludao Central Hospital, Huludao, 125000, People’s Republic of China; 3Department of Radiation Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, People’s Republic of China; 4Department of Cardiovascular Medicine, Chinese PLA Unit 92493 Hospital, Huludao, 125000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Miaomiao Lu, Email [email protected]: Acute kidney injury (AKI) is a severe clinical condition with high morbidity and mortality that lacks effective therapies. Carbon dots (CDs) derived from traditional Chinese medicine ingredients have emerged as promising therapeutic agents because of their favorable biosafety profile and potent antioxidant and anti-inflammatory properties. In this study, the therapeutic effects of CDs derived from Ligusticum chuanxiong (LC-CDs) were investigated in an ischemia‑reperfusion injury AKI model, and their underlying molecular mechanisms were elucidated.Methods: LC-CDs were developed through a facile hydrothermal method and were used to treat an ischemia-reperfusion AKI rat model and HK-2 cells with hypoxia/reoxygenation injury.Results: LC-CDs with uniform nanostructures, graphitic carbon structures, and multiple chemical functional groups on the surface were successfully synthesized. The LC-CDs exhibited excellent hydrophilicity, chemical reactivity, and unique optical properties. Treatment with the LC-CDs significantly reduced creatinine and blood urea nitrogen levels and alleviated pathological damage in renal tissue. Additionally, the LC-CDs effectively cleared reactive oxygen species, reduced oxidative stress levels, and mitigated mitochondrial damage. Treatment with the LC-CDs also decreased renal tissue expression of key inflammatory factors (IL-1β, IL-6, and TNF-α). Transcriptome analysis revealed that differentially expressed genes associated with the LC‑CDs were primarily involved in the autophagy, and inflammatory signaling pathways. Further subcellular fractionation and fluorescence localization analyses confirmed that the LC-CDs accumulated in and targeted mitochondria, suggesting that mitochondria are the primary organelle target through which the LC-CDs exert their effects. Autophagy-related signaling pathways likely also played a critical role in mediating the therapeutic efficacy of the LC-CDs.Conclusion: The LC-CDs demonstrated considerable therapeutic potential in an AKI model through their antioxidant, anti-inflammatory, and autophagy regulation. Their outstanding biocompatibility, multifunctional synergistic properties, and well-defined molecular targets provide a crucial foundation for the development of novel nanomedicines and kidney-targeted delivery systems.Keywords: carbon quantum dots, Ligusticum chuanxiong, acute kidney injury, oxidative stress, mitochondrial homeostasis