Open AccessGypenosides improve diabetic cardiomyopathy by inhibiting ROS ‐mediated NLRP 3 inflammasome activation
Author(s) -
Zhang Hailong,
Chen Xi,
Zong Beibei,
Yuan Hongmin,
Wang Zhizeng,
Wei Yinxiang,
Wang Xuance,
Liu Guangchao,
Zhang Jun,
Li Shulian,
Cheng Guanchang,
Wang Yaohui,
Ma Yuanfang
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13743
Subject(s) - inflammasome , reactive oxygen species , chemistry , cytochrome c , microbiology and biotechnology , medicine , pharmacology , biology , biochemistry , mitochondrion , receptor
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.