Unlocking the potential: Baicalin's apoptosis-reducing power and activation of NRF2/P62 for alleviating diabetic cardiomyopathy in rats

Background

Baicalin has been proven to have the potential to reduce apoptosis and diabetic cardiomyopathy (DCM). However, the mechanism behind this effect still needs to be fully understood.

Objectives

To explore the potential therapeutic properties of Baicalin in managing DCM and controlling glycemic levels.

Results

In this study, Baicalin (at doses of 20, 60, or 120 mg/kg/d) were used to treat diabetic rats. At the end of treatment, the heart function of the rats was assessed. Furthermore, their serum levels of TG, TC, and LDL were measured using the ELISA method. Cell viability was evaluated using the CCK8 assay and apoptosis was assessed using flow cytometry or TUNEL assay. Primary cardiomyocytes were infected with NRF2 siRNA and then treated with Baicalin while incubating with high glucose (25 mmol/L). Protein and mRNA variations were analyzed using Western blot and qRT-PCR, respectively. The study found that when given Baicalin, diabetic rats demonstrated improved heart function. Without treatment, the hearts of diabetic rats displayed elevated levels of apoptotic cell death and cardiomyocyte autophagy, as well as decreased expressions of NRF2, HO-1, and KEAP1. However, Baicalin was able to reverse all of these diabetes-induced biochemical changes. Treatment enhanced NRF2 nuclear transfer, reduced hyperglycemia-induced apoptosis and autophagy in primary cardiomyocytes, and improved cellular viability in in vitro experiments. It must be noted that the protective effects of Baicalin were only observed when the Nrf2 gene expression was present in primary cardiomyocytes.

Conclusion

Baicalin may reduce the effects of DCM by activating NRF2 through KEAP1 suppression and regulating autophagy activation.