Background: There is a close relationship between heart failure and insulin resistance, it is of great significance to carry out research on prevention and treatment of heart failure based on insulin resistance. Ginsenoside Rg3 is one of the main active ingredients in ginseng. Here, we confirmed its protective effect on the heart function of TAC-induced heart failure mice and aimed to explore the potential molecular mechanisms involved.
Methods: The effects of ginsenoside Rg3 on heart function and mitochondrial function were investigated by treating TAC-induced heart failure in mice. The mechanism of ginsenoside Rg3 to improve heart function and mitochondrial function in mice with heart failure was predicted through integrative analysis of proteome and plasma metabolome. Glucose uptake and myocardial insulin sensitivity were evaluated using micro-PET. Based on the above work, this experiment clarified the effect of ginsenoside Rg3 on myocardial insulin sensitivity by combining in vivo animal experiments and in vitro cell experiments. In vivo , the related protein expression levels of IRS-PI3K-Akt signaling pathway were detected. In vitro , the IR-H9c2 cardiomyocyte model was replicated with high-concentration insulin treatment, the 2-NBDG glucose uptake and transport probe was used to detect the glucose uptake of the cells, and the Western blotting method was used to detect the phosphorylation level of AMPK.
Results: Treatment of TAC-induced mouse models with ginsenoside Rg3 significantly reduced myocardial hypertrophy, delayed ventricular remodeling, improved contractile and diastolic dysfunction, and protected mitochondrial structure and function. Fusion of metabolomics, proteomics and targeted metabolomics data showed that Rg3 could regulate the glycolysis process, and it has been further confirmed that Rg3 could not only regulate glucose uptake but also improve myocardial insulin resistance by using micro-PET in a mouse model of heart failure. The molecular mechanism of ginsenoside Rg3 regulating glucose metabolism was clearly determined by exploring the interaction pathways of AMPK, insulin resistance and glucose metabolism. The results showed that the effect of ginsenoside Rg3 on the promotion of glucose uptake in IR-H9c2 cells by AMPK activation was dependent on the insulin signaling pathway.
Conclusions: Ginsenoside Rg3 modulates glucose metabolism and significantly ameliorates insulin resistance through activation of AMPK pathway.
