Flos Puerariae Extract Prevents Myocardial Apoptosis via Attenuation Oxidative Stress in Streptozotocin-Induced Diabetic Mice

Abstract

BackgroundDiabetic cardiomyopathy (DCM) suggests a direct cellular insult to myocardium. Apoptosis is considered as one of the hallmarks of DCM. Oxidative stress plays a key role in the pathogenesis of DCM. In this study, we explored the prevention of myocardial apoptosis by crude extract from Flos Puerariae (FPE) in experimental diabetic mice.MethodsExperimental diabetic model was induced by intraperitoneally injection of streptozotocin (STZ, 50 mg/kg/day) for five consecutive days in C57BL/6J mice. FPE (100, 200 mg/kg) was orally administrated once a day for ten weeks. Cardiac structure changes, apoptosis, superoxide production, NADPH oxidase subunits expression (gp91phox, p47phox, and p67phox), and related regulatory factors were assessed in the heart of mice.ResultsDiabetic mice were characterized by high blood glucose (≥11.1 mmol/L) and reduced body weight. In the end of the experiment, aberrant myofilament structure, as well as TUNEL positive cardiac cells coupled with increased Bax/Bcl-2 ratio and Caspase-3 expression was found in diabetic mice. Moreover, ROS formation, the ratio of NADP+/NADPH and NADPH oxidase subunits expression of gp91phox and p47phox, lipid peroxidation level was significantly increased, while antioxidant enzyme SOD and GSH-Px activity were reduced in the myocardial tissue of diabetic mice. In contrast, treatment with FPE resulted in a normalized glucose and weight profile. FPE administration also preserved myocardial structure and reduced apoptotic cardiac cell death in diabetic mice. The elevated markers of oxidative stress were significantly reversed by FPE supplementation. Further, FPE treatment markedly inhibited the increased Bax/Bcl-2 ratio and Caspase-3 expression, as well as suppressed JNK and P38 MAPK activation in the heart of diabetic mice.ConclusionsOur data demonstrate for the first time that FPE may have therapeutic potential for STZ-induced diabetic cardiomyopathy through preventing myocardial apoptosis via attenuation oxidative stress. And this effect is probably mediated by JNK and P38 MAPK signaling pathway.

The Use of Natural Products in the Management of Diabetes: The Current Trends

“…Flos puerariae (FPE): FPE was shown to inhibit gp91 phox and p47 phox, the two subunits of NOX in the hearts of STZinduced C57BL/6J diabetic mice [39] . Additionally, FPE inhibited the DM-induced ROS generation and enhanced the activity of SOD and glutathione peroxidase (GSH-Px), maintained myocardial structure, and attenuated DMinduced apoptotic cardiac cell death [39] . Thus, FPE had the capability to both inhibit NOX expression and upregulate the expression of antioxidants in the hearts of the diabetic mice.…”

Emerging Risk Biomarkers in Cardiovascular Diseases and Disorders

“…Similarly, α 4 β 7 Integrin (LPAM-1) is also found to be related to atherosclerosis progression [ 48 ]. Serum metabolic profiling [ 176 ] and serum total p-cresyl sulfate level are measured to predict CVD risks mainly in angina patients [ 177 ] ( Figure 4 ). There are some accessory factors such as alcohol, smoking, obesity, arterial thickness, BMI, and respiration rate which increase cardiovascular severity many times [ 178 ].…”

“…However, cardiac structure changes, apoptosis, superoxide production, NADPH oxidase subunits expression (gp91phox, p47phox, and p67phox), and related regulatory factors such as high blood glucose level and reduced body weight are considered to be good markers of DCM. FPE may have therapeutic potential for STZ-induced diabetic cardiomyopathy through preventing myocardial apoptosis via attenuation of oxidative stress that is probably mediated by JNK and P38 MAPK signaling pathways [ 176 ] ( Table 2 ).…”

miR-483-3p regulates hyperglycaemia-induced cardiomyocyte apoptosis in transgenic mice

“…Diabetics with heart disease have a poor prognosis as compared to non-diabetics with a similar heart condition [2]. Diabetic cardiomyopathy is described as presence of impaired myocardial structure and heart function due to DM, independent of hypertension or coronary artery disease [3].…”