Gypenosides improve diabetic cardiomyopathy by inhibiting ROS ‐mediated NLRP 3 inflammasome activation

NLRP 3 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 NLRP 3 inflammasome and then promoting IL ‐1β and IL ‐18 secretion in H9C2 cells and NRVM s. Meanwhile, HG elevated the production of ROS , which was vital to NLRP 3 inflammasome activation. Moreover, the ROS activated the NLRP 3 inflammasome mainly by cytochrome c influx into the cytoplasm and binding to NLRP 3. Inhibition of ROS and cytochrome c dramatically down‐regulated NLRP 3 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 ( CRP s), IL ‐1β and IL ‐18, inhibited NLRP 3 inflammasome activation and consequently improved myocardial damage in vivo. These findings provide a mechanism that ROS induced by HG activates the NLRP 3 inflammasome by cytochrome c binding to NLRP 3 and that Gps may be potential and effective drugs for DCM via the inhibition of ROS ‐mediated NLRP 3 inflammasome activation.