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Apigenin is an important component of fruit and vegetable in human daily diets. Several cellular and animals models had been performed for showing its anti-oxidant and anti-inflammatory bioactivities. However, the cardioprotective effects of apigenin in diabetic cardiomyopathy remain unclear. In this study, we intended to explore the roles of apigenin in cardiac remodeling of diabetic cardiomyopathy.
Male C57BL/6J mice were fed a high-fat diet for 3 months to induced insulin resistance, followed by a treatment with STZ (100mg/kg) to induce hyperglycemia to establish the model of type 2 diabetes mellitus (T2DM). The control group mice were fed normal diet. T2DM and control mice were treated with or without apigenin at 100mg/kg daily without incessantness in another 4 months. The echocardiography and catheter-based measurements of hemodynamic parameters were performed to evaluate the cardiac function. Parafin slices of harvested hearts were prepared for Histological analysis and TUNEL assay. Oxidative assay kit was used to detect GSH-Px, MDA and SOD. Western-blot and real time-PCR were used for access the expression of protein and mRNA. Finally, H9c2 treatment with high glucose or apigenin was used for further investigation in vitro.
Apigenin treatment significantly improves the dysfunction of the diabetic hearts, and attenuated cardiac fibrosis induced by T2DM. The immunohistochemistry showed that diabetes mellitus significantly induced the over-accumulation of 4-hydroxynonenal in the cardiac tissue, which can be down-regulated by treatment with apigenin accompanying with decreasing of GSH-Px, MDA and SOD. The enhanced activity of caspase3 and NF-κB/P65 can also be blunted by apigenin. Besides, the apoptotic nucleuses in treatment group were much less than that in diabetic cardiomyopathy group. In vitro experiment, we further demonstrated that apigenin could inhibit the translocation of NF-κB and down-regulate the expression of Bax and cleaved-caspase3.
Both in vitro and in vivo investigation suggested that apigenin might be a promising supplement for against cardiac remodeling in diabetic cardiomyopathy. Our experiments indicated that the regulatory roles of apigenin might be involved in the regulation of oxidative stress, blunting NF-kB signaling pathway and inhibition of apoptosis.