Tao Hong Si Wu decoction attenuates myocardial injury in diabetic mice by regulating the cGAS/STING/NLRP3 axis

Tao Hong Si Wu decoction (TSD) has been shown to improve cardiac structure and function in diabetic cardiomyopathy (DCM), although the underlying mechanism remains unclear. This used 8-week-old male db/db and db/m diabetic mice, and measured the levels of blood glucose, triglycerides (TG), low-density lipoprotein Cholesterol (LDL-C), high-density lipoprotein Cholesterol (HDL-C), total Cholesterol (TC), Creatine Kinase (CK), B-natriuretic peptide (BNP), malondialdehyde (MDA), and superoxide dismutase (SOD). Cardiac function was assessed using echocardiography, and mitochondrial ultrastructure was evaluated. Gene expression levels were measured using Western blotting and RT-qPCR, and immunohistochemistry was used to assess IL-1β, TNF-α, and IL-6 levels. HL-1 cardiomyocytes were treated with PA, and cell viability and mitochondrial membrane potentials were evaluated. It was found that TSD reduced the heart weight to tibia length (HW/TL) ratio, TC, TG, and LDL-C levels, improved cardiac dysfunction, and increased the HDL-C level. Reductions in the Collagen volume fraction (CVF) and levels of myocardial fibrosis, oxidative stress injury, and mitochondrial damage were observed, as well as decreased concentrations of inflammatory factors. Treatment with TSD also ameliorated PA-induced Apoptosis, decreased MDA levels, and increased the levels of SOD. The mitochondrial membrane potential was significantly enhanced, as well as marked inhibition of Pyroptosis. It was found that TSD inhibited PA-induced cGAS-STING pathway activation and subsequent Pyroptosis in HL-1 cells. In conclusion, TSD improved diabetes-induced structural and functional damage to the heart by reducing Pyroptosis and inflammatory damage in cardiomyocytes.

CGAS–STING–NLRP3 axis; Diabetic cardiomyopathy; Pyroptosis; Tao Hong Si Wu decoction.