PMID- 29993180
OWN - NLM
STAT- MEDLINE
DCOM- 20191029
LR  - 20210109
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 22
IP  - 9
DP  - 2018 Sep
TI  - Gypenosides improve diabetic cardiomyopathy by inhibiting ROS-mediated NLRP3 
      inflammasome activation.
PG  - 4437-4448
LID - 10.1111/jcmm.13743 [doi]
AB  - 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-1beta 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-1beta 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.
CI  - (c) 2018 The Authors. Journal of Cellular and Molecular Medicine published by John 
      Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
FAU - Zhang, Hailong
AU  - Zhang H
AUID- ORCID: 0000-0003-3316-4290
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of 
      Cellular and Molecular Immunology of Henan Province, School of Basic Medicine, 
      Henan University, Kaifeng, China.
FAU - Chen, Xi
AU  - Chen X
AD  - Department of General Pathology, Huaihe Hospital, Henan University, Kaifeng, 
      China.
FAU - Zong, Beibei
AU  - Zong B
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of 
      Cellular and Molecular Immunology of Henan Province, School of Basic Medicine, 
      Henan University, Kaifeng, China.
FAU - Yuan, Hongmin
AU  - Yuan H
AD  - Department of Thyroid Breast Surgery, Huaihe Hospital, Henan University, Kaifeng, 
      China.
FAU - Wang, Zhizeng
AU  - Wang Z
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of 
      Cellular and Molecular Immunology of Henan Province, School of Basic Medicine, 
      Henan University, Kaifeng, China.
FAU - Wei, Yinxiang
AU  - Wei Y
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of 
      Cellular and Molecular Immunology of Henan Province, School of Basic Medicine, 
      Henan University, Kaifeng, China.
FAU - Wang, Xuance
AU  - Wang X
AD  - Centre for Translational Medicine, Huaihe Hospital, Henan University, Kaifeng, 
      China.
FAU - Liu, Guangchao
AU  - Liu G
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of 
      Cellular and Molecular Immunology of Henan Province, School of Basic Medicine, 
      Henan University, Kaifeng, China.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of 
      Cellular and Molecular Immunology of Henan Province, School of Basic Medicine, 
      Henan University, Kaifeng, China.
FAU - Li, Shulian
AU  - Li S
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of 
      Cellular and Molecular Immunology of Henan Province, School of Basic Medicine, 
      Henan University, Kaifeng, China.
FAU - Cheng, Guanchang
AU  - Cheng G
AD  - Department of Cardiac Surgery, Huaihe Hospital, Henan University, Kaifeng, China.
FAU - Wang, Yaohui
AU  - Wang Y
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of 
      Cellular and Molecular Immunology of Henan Province, School of Basic Medicine, 
      Henan University, Kaifeng, China.
FAU - Ma, Yuanfang
AU  - Ma Y
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of 
      Cellular and Molecular Immunology of Henan Province, School of Basic Medicine, 
      Henan University, Kaifeng, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180711
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Antioxidants)
RN  - 0 (Blood Glucose)
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Carrier Proteins)
RN  - 0 (Crp protein, rat)
RN  - 0 (IL1B protein, rat)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, rat)
RN  - 0 (Plant Extracts)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (gypenoside)
RN  - 5W494URQ81 (Streptozocin)
RN  - 9007-43-6 (Cytochromes c)
SB  - IM
MH  - Animals
MH  - Antioxidants/isolation & purification/*pharmacology
MH  - Blood Glucose/drug effects/metabolism
MH  - Cardiotonic Agents/isolation & purification/*pharmacology
MH  - Carrier Proteins/genetics/metabolism
MH  - Cell Line
MH  - Cytochromes c/genetics/metabolism
MH  - Diabetes Mellitus, Experimental/chemically induced/*drug 
      therapy/genetics/pathology
MH  - Diabetic Cardiomyopathies/chemically induced/*drug therapy/genetics/pathology
MH  - Gene Expression Regulation
MH  - Gynostemma/chemistry
MH  - Inflammasomes/*drug effects/metabolism
MH  - Interleukin-18/genetics/metabolism
MH  - Interleukin-1beta/genetics/metabolism
MH  - Male
MH  - Myocytes, Cardiac/cytology/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/agonists/*genetics/metabolism
MH  - Oxidative Stress
MH  - Plant Extracts/isolation & purification/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/antagonists & inhibitors/metabolism
MH  - Signal Transduction
MH  - Streptozocin
PMC - PMC6111804
OTO - NOTNLM
OT  - NLRP3 inflammasome
OT  - ROS
OT  - cytochrome c
OT  - diabetic cardiomyopathy
OT  - gypenosides
OT  - high glucose
EDAT- 2018/07/12 06:00
MHDA- 2019/10/30 06:00
PMCR- 2018/09/01
CRDT- 2018/07/12 06:00
PHST- 2018/04/10 00:00 [received]
PHST- 2018/05/26 00:00 [accepted]
PHST- 2018/07/12 06:00 [pubmed]
PHST- 2019/10/30 06:00 [medline]
PHST- 2018/07/12 06:00 [entrez]
PHST- 2018/09/01 00:00 [pmc-release]
AID - JCMM13743 [pii]
AID - 10.1111/jcmm.13743 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2018 Sep;22(9):4437-4448. doi: 10.1111/jcmm.13743. Epub 2018 Jul 
      11.