A novel nanomicelle based on Rebaudioside A: An oral nanoplatform with enhanced nephroprotective effect of myricetin

Cisplatin-induced acute kidney injury (AKI) is a significant clinical challenge, primarily characterized by inflammatory responses and oxidative stress. This study aimed to develop a myricetin (Myr) loaded Rebaudioside A (RA) nanomicelle delivery system (RA-Myr) and investigate its nephroprotective effects both <i>in vitro</i> and <i>in vivo</i>. RA-Myr nanomicelles were prepared using a thin film hydration method. The characterization of RA-Myr included evaluating particle size, encapsulation efficiency, and stability. The antioxidant capacity of RA-Myr was assessed using the FRAP assay, and cellular uptake was evaluated using coumarin 6-loaded RA nanomicelles. The protective effects and potential mechanisms of RA-Myr on cisplatin-induced AKI were studied in HK-2 cells and male Kunming mice. RA-Myr significantly inhibited cisplatin-induced suppression of HK-2 cell proliferation, reduced ROS accumulation, and restored mitochondrial membrane potential. <i>In vivo</i>, RA-Myr alleviated cisplatin-induced AKI, evidenced by decreased blood urea nitrogen (BUN) and serum creatinine (SCr) levels, and mitigated kidney tissue pathological damage. Mechanistically, RA-Myr protected against cisplatin-induced DNA damage and inhibited the cGAS-STING pathway. The RA-Myr nanomicelle delivery system shows promise as a potential strategy for alleviating cisplatin-induced AKI by enhancing the nephroprotective effects of Myr.