Curcumin Improves Diabetic Cardiomyopathy by Inhibiting Pyroptosis through AKT/Nrf2/ARE Pathway

Abstract

This study is aimed at exploring whether curcumin can regulate the AKT pathway, promote the transfer of Nrf2 into the nucleus, and inhibit cell pyroptosis in diabetic cardiomyopathy. Diabetic rats and cardiomyocytes were treated with curcumin to study its effect on myocardial pyroptosis. Whether curcumin can promote the transfer of Nrf2 into the nucleus through AKT pathway regulation was assessed by western blotting and immunofluorescence. The Nrf2 knockout vector and ml385 were used to block the Nrf2 pathway, and the differences between the different groups in the expression of pyroptosis protein, cell activity, and incidence of apoptosis were evaluated to verify the relationship between the effect of curcumin on pyroptosis inhibition and the Nrf2 pathway. Curcumin promoted the transfer of Nrf2 into the nucleus through the AKT pathway and increased the expression of the antioxidant factors HO-1 and GCLC. These effects reduced reactive oxygen species accumulation and mitochondrial damage in diabetic myocardium and inhibited diabetes-induced pyroptosis. However, in cardiomyocytes with a blocked Nrf2 pathway, the ability of curcumin to inhibit pyroptosis was significantly reduced, and the protective effect on the cells was lost. Curcumin can reduce the accumulation of superoxide in the myocardium through AKT/Nrf2/ARE pathway activation and inhibit pyroptosis. It also has a role in diabetic cardiomyopathy treatment. This study provides new directions for evaluating the mechanism of diabetic cardiomyopathy and treating diabetic myocardium.

Bardoxolone methyl attenuates doxorubicin‐induced cardiotoxicity by inhibiting the TXNIP–NLRP3 pathway through Nrf2 activation

“…A cellular model of doxorubicin‐induced cardiotoxicity was established by co‐incubating H9c2 cells with doxorubicin at a concentration of 1 μM. The concentration of nigericin (an activator of NLRP3) used in the experiments was 10 μM, which has been confirmed in previous studies 23 …”

“…Bardoxolone methyl (10 mg/mL) dissolved in dimethyl sulfoxide (DMSO) was administered weekly by ip injection (10 mg/kg body weight) for 6 weeks 22 . Additionally, ML385 (5 mg/mL) dissolved in DMSO was administered weekly by ip injection (20 mg/kg body weight) for 6 weeks 23 . Animals that served as controls were injected with the same volume of DMSO or normal saline alone.…”

Role of pyroptosis in diabetic cardiomyopathy: an updated review

“…The expression of NLRP3, caspase-1, IL-18, and IL-1b was also significantly increased. Meanwhile, DM rats treated with ML385 to suppress Nrf2 showed more severe myocardial fibrosis and cardiac enlargement (101). All of these studies provide valuable evidence that the Nrf2-related pathway may serve as a future target for treating DCM.…”

Diabetes cardiomyopathy: targeted regulation of mitochondrial dysfunction and therapeutic potential of plant secondary metabolites

“…In a rat model of SD diabetes established by HFD and intraperitoneal injection of STZ, curcumin (200 mg/kg/d) treatment for 8 months promoted the transfer of Nrf2 to the nucleus through the AKT pathway, increased the expression of the antioxidant factors HO-1 and GCLC, reduced the accumulation of mitochondrial ROS, and mitigated mitochondrial oxidative damage. The study suggests that curcumin inhibits cell apoptosis by activating the AKT/Nrf2/ARE pathway and eliminates the accumulation of superoxide in myocardial cells ( Wei et al, 2023 ). Additionally, Yao et al research has shown that curcumin can upregulate the expression of AMPK and JNK1 to stimulate mitophagy, as well as upregulate the expression of Bcl-2 and Bim to reduce cardiomyocyte apoptosis.…”