Puerarin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of inflammation.

Diabetic cardiomyopathy (DCM) is one of the chief diabetes mellitus complications. Inflammation factors may be one reason for the damage from DM. The purpose of this research is to study the potential protective effects of puerarin on DM and the possible mechanisms of action related to NF-κB signal pathway. Following administration of puerarin to the disease model rat, several changes were observed including the changes of serum biochemical index, improved diastolic dysfunction, and enhanced endogenous antioxidant enzymes activities, further NF-κB signaling activation. Puerarin showed cardio-protective effects on DCM by inhibiting inflammation, and it might be a potential candidate for the treatment of DCM.

Methylamine irisolidone, a novel compound, increases total ATPase activity and inhibits apoptosis in vivo and in vitro.

We propose to further research the protective effect of MMI on myocardium ischemic rat model and H9c2 cells that underwent cell apoptosis induced by hypoxia. We established the myocardium ischemic rat model via the cardiac surgical procedures in vivo and treated the model rats with different concentration of MMI. In vitro, with the pretreatment of MMI for 12 h in the model of Na2S2O4-induced hypoxia injury, the H9c2 cells viability was determined by MTT assay. We found that MMI had significantly improved cardiac function of the myocardial ischemia, and significantly decreased the reactive oxygen species level. The expression of P53, Bcl-2, Bax, and caspase-9 was also induced by MMI. In vitro study revealed a concentration-dependent increase in cell viability associated with MMI pretreatment. Annexin V-FITC and PI staining results showed that MMI had a preventive effect on hypoxia-induced apoptosis in H9c2 cells. MMI also inhibited the mitochondrial membrane potential decrease and increased total ATPase activity during hypoxia in H9c2 cells. In conclusion, MMI can enhance the cardiac function in myocardial ischemic rat and increase cell viability and attenuate the apoptosis in H9c2 cells induced by hypoxia, which was associated with inhibiting MMP decreasion and increasing total ATPase activity.

Activation of Wnt/ß-catenin/GSK3ß signaling during the development of diabetic cardiomyopathy.

BACKGROUND: As Wnt/ß-catenin/glycogen synthase kinase 3ß (GSK3ß) signaling has been implicated in myocardial injury and diabetic cardiomyopathy (DCM) is a major part of diabetic cardiovascular complications, we therefore investigated the alterations of Wnt/ß-catenin/GSK3ß signaling during the development of DCM. METHODS: The rat model of diabetes mellitus (DM) was established using a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). The alterations of Wnt/ß-catenin/GSK3ß signaling were determined 4, 8, and 12 weeks following DM using Western blotting, immunohistochemistry, and quantitative real-time reverse transcriptase polymerase chain reaction. Cardiac pathology changes were evaluated using hematoxylin and eosin, Masson trichromatic, and terminal dUTP nick-end labeling staining. RESULTS: Histological analyses revealed that DM induced significant myocardial injury and progressive cardiomyocyte apoptosis. The protein and mRNA levels of Wnt2, ß-catenin, and c-Myc were progressively increased 4, 8, and 12 weeks following DM. The expression of T-cell factor 4 and phosphorylated of GSK3ß on Ser9 were progressively increased. However, the expression of the endogenous Wnt inhibitor Dickkopf-1 was increased after STZ injection and then decreased as DCM developed. CONCLUSION: Wnt/ß-catenin/GSK3ß signaling pathway is activated in the development of DCM. Further investigation into the role of Wnt signaling during DCM will functionally find novel therapeutic target for DCM.