Jinxinkang Granule Preserves Myocardial Function by Suppressing Cardiac Senescence Through the cGAS-STING Axis in a Pressure Overload Mouse Model of Heart Failure.

Heart failure (HF) is a major cause of morbidity and mortality, and current therapies do not fully prevent adverse remodeling. Traditional Chinese medicine (TCM) formulas are increasingly explored as adjunctive strategies for HF; however, their efficacy and mechanisms require further validation. This study investigated whether Jinxinkang granule (JXK), a clinically used TCM formula, protects against pressure overload-induced HF in mice, and further explored the molecular mechanisms underlying its cardioprotective effects. Pressure overload HF was induced by transverse aortic constriction (TAC) in male C57BL/6J mice. Animals were randomized into control, model, JXK (low, medium, high dose), or positive control (trimetazidine) groups. Cardiac function was assessed by echocardiography, serum biomarkers (NT-proBNP, CK-MB, cTnT) were measured, and cardiac remodeling was assessed by hematoxylin and eosin staining, Masson's trichrome staining, wheat germ agglutinin staining, and TUNEL assay. Expression of senescence markers (p16, p53, MMP3) and cGAS-STING pathway components was analyzed by qPCR, Western blotting, and immunofluorescence. TAC induced systolic dysfunction, ventricular dilation, cardiomyocyte hypertrophy, fibrosis, and increased apoptosis, accompanied by activation of senescence markers and of cGAS-STING signaling. JXK dose-dependently improved left ventricular ejection fraction and fractional shortening, reduced serum injury biomarkers, attenuated cardiomyocyte hypertrophy and fibrosis, and decreased TUNEL-positive cells. Mechanistically, JXK suppressed TAC-induced upregulation of p16, p53, and MMP3, and inhibited cGAS, STING, p-TBK1, and p-IRF3 activation. JXK preserves cardiac function and attenuates remodeling in pressure overload-induced HF, potentially through inhibition of myocardial senescence and suppression of the cGAS-STING pathway.