Protective mechanisms of Qingda granule in hypertensive kidney injury: Focus on ERK/RSK1-mediated mitochondrial protection

Hypertension is a significant chronic non-infectious disease in China, with Qingda Granule (QDG) historically used for its management. However, the mechanisms underlying QDG's kidney protective effects remain unclear. This study investigates the role of QDG in mitigating hypertensive kidney injury (KI) and explores the associated mechanisms. Network analysis identified potential therapeutic targets related to mitochondrial function and the ERK cascade. RNA sequencing revealed differentially expressed genes in hypertensive mouse kidneys, which were enriched in mitochondrial-related functions and reversed by QDG treatment. QDG also reduced Angiotensin II (Ang II)-induced blood pressure elevation and improved renal artery flow. Both cellular and animal experiments demonstrated that QDG inhibits the ERK/RSK1 signaling axis, thereby preventing Ang II-induced mitochondrial damage and renal cell apoptosis. The use of ERK pathway inhibitors further confirmed that QDG exerts its effects through the ERK/RSK1 pathway. These findings suggest that QDG alleviates hypertensive KI by minimizing mitochondrial damage through modulation of the ERK/RSK1 network, offering a novel approach for managing hypertensive KI in clinical settings.