Gypenosides improve diabetic cardiomyopathy by inhibiting ROS-mediated NLRP3 inflammasome activation.

NLRP3 inflammasome activation plays an important role in diabetic cardiomyopathy (DCM), which may relate to excessive production of reactive oxygen species (ROS). Gypenosides (Gps), the major ingredients of Gynostemma pentaphylla (Thunb.) Makino, have exerted the properties of anti-hyperglycaemia and anti-inflammation, but whether Gps improve myocardial damage and the mechanism remains unclear. Here, we found that high glucose (HG) induced myocardial damage by activating the NLRP3 inflammasome and then promoting IL-1ß and IL-18 secretion in H9C2 cells and NRVMs. Meanwhile, HG elevated the production of ROS, which was vital to NLRP3 inflammasome activation. Moreover, the ROS activated the NLRP3 inflammasome mainly by cytochrome c influx into the cytoplasm and binding to NLRP3. Inhibition of ROS and cytochrome c dramatically down-regulated NLRP3 inflammasome activation and improved the cardiomyocyte damage induced by HG, which was also detected in cells treated by Gps. Furthermore, Gps also reduced the levels of the C-reactive proteins (CRPs), IL-1ß and IL-18, inhibited NLRP3 inflammasome activation and consequently improved myocardial damage in vivo. These findings provide a mechanism that ROS induced by HG activates the NLRP3 inflammasome by cytochrome c binding to NLRP3 and that Gps may be potential and effective drugs for DCM via the inhibition of ROS-mediated NLRP3 inflammasome activation.

Cardiac effects of fish oil in a rat model of streptozotocin-induced diabetes.

BACKGROUND AND AIMS: Fish oil (FO) is rich in omega-3 polyunsaturated fatty acids, which have cardio-protective effects. This study aims to evaluate effects of FO in a rat model of streptozotocin (STZ) induced diabetes. METHODS AND RESULTS: Adults male Wistar rats were assigned to control (4 µl corn oil/g corn oil given by oral gavage), FO (4 µl Menhaden FO/g body weight given by oral gavage), diabetes (DM, 35 mg/kg STZ single intraperitoneal injection, corn oil), and DM + FO groups for 8 weeks. Plasma and cardiac biomarkers of oxidative stress, inflammation, and fibrosis were evaluated. STZ-induced diabetes as indicated by the significant increase in serum levels of glucose and percentage of glycated hemoglobins. FO reduced plasma arachidonic acid (AA) percentage and ratio of AA: docosahexaenoic acid (DHA). Plasma and cardiac levels of total nitrite, endothelin -1 (ET-1), and myeloperoxidase (MPO) increased in the DM group, whereas cardiac activities of catalase and superoxide dismutase (SOD) decreased. FO reduced cardiac nitrite and MPO, and plasma ET-1 levels. FO increased cardiac glutathione, catalase and SOD activities. Levels of thiobarbituric acid substances increased in the FO and DM groups with significant synergism in the DM + FO group. FO prevented cardiac fibrosis associated with DM and decreased cardiac transforming growth factor beta-1and p38 MAP kinases. Cardiac levels of matrix metalloproteinase -2 were significantly elevated in FO and DM + FO groups. CONCLUSIONS: FO decreased plasma and cardiac oxidative stress, inflammation and myocardial fibrosis. FO could be used in diabetes to reduce risk and burden of CVDs.

Dendrobium officinale Kimura et Migo attenuates diabetic cardiomyopathy through inhibiting oxidative stress, inflammation and fibrosis in streptozotocin-induced mice.

Dendrobium officinale Kimura et Migo (Dendrobium catenatum Lindley), a prized traditional Chinese Medicine, has been used in China and Southeast Asian countries for centuries. The present study was aimed to investigate the effects and the possible mechanisms of the Dendrobium officinale extracts (DOE) on diabetic cardiomyopathy in mice. The diabetic model was induced by intraperitoneal injection of streptozotocin at the dose of 50mg/kg body weight for 5 consecutive days. After 8 weeks treatment of DOE, mice were sacrificed, blood sample and heart tissues were collected. Our results showed that Streptozotocin-induced diabetic model was effectively achieved and serum CK and LDH levels were significantly increased in mice with diabetic cardiomyopathy. Pretreatment with DOE decreased the heart-to-body weight ratio (HW/BW) and showed an evident hypoglycemic effect. DOE pretreatment significantly decreased CK, LDH, TC and TG levels, limited the production of MDA and increased the activities of T-SOD. The histological analysis of Oil red O staining and Sirius red staining showed an obvious amelioration of cardiac injury, inhibition of cardiac lipid accumulation and deposition of collagen when pretreatment with DOE. In addition, Western blot detection and analysis showed that DOE down-regulated the expression of TGF-ß, collegan-1, fibronectin, NF-κB, TNF-α and IL-1ß. In conclusion, our study suggested that DOE possesses the cardioprotective potential against diabetic cardiomyopathy, which may be due to the inhibition of oxidative stress, cardiac lipid accumulation, pro-inflammatory cytokines and cardiac fibrosis.

Ficus recemosa bark extract attenuates diabetic complications and oxidative stress in STZ-induced diabetic rats.

Context Ficus recemosa Linn. (Moraceae) has been reported as a natural folk medicine with diverse pathological activities such as antioxidant, antidiabetic, renoprotective and cardioprotective. Objective The present study evaluates the preventive effect of standardised ethanol extract of F. racemosa stem bark (EEFSB) on diabetic cardiomyopathy (DC) and diabetic nephropathy (DN). Materials and methods Animals were rendered diabetic by one time administration of STZ (45 mg kg(-1), i.v.) and, after 7 d, diabetic rats were randomised into four groups of eight rats each. EEFSB (200 and 400 mg kg(-1)) was administered to diabetic rats once daily for 8 weeks. Furthermore, the presence of phytochemicals was evaluated by HPTLC. Results Treatment with EEFSB markedly restores the blood glucose and lipid level (p < 0.001), also reduced creatinine kinase (p < 0.001), lactate dehydrogenase (p < 0.001), C-reactive protein (p < 0.001), creatinine (p < 0.001), blood urea nitrogen (p < 0.001), collagen (p < 0.05) and albumin (p < 0.001) levels. Reduced level of sodium (p < 0.001), creatinine (p < 0.001), albumin (p < 0.001) and malondialdehyde (p < 0.01) in heart and kidney tissue along with enhanced activities of superoxide dismutase (p < 0.001) and reduced glutathione (p < 0.001). Moreover, left ventricular hypertrophic index and cardiac hypertrophic index were markedly reduced by EEFSB treatment. Conclusion The findings of this study provided strong scientific evidence for the traditional use of F. racemosa and postulate protective effects against diabetes and its complications such as DC and DN.