PMID- 28983604
OWN - NLM
STAT- MEDLINE
DCOM- 20180625
LR  - 20211204
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 16
IP  - 6
DP  - 2017 Dec
TI  - Sanggenon C protects against cardiomyocyte hypoxia injury by increasing 
      autophagy.
PG  - 8130-8136
LID - 10.3892/mmr.2017.7646 [doi]
AB  - Sanggenon C is isolated from Morus alba, a plant that has been used for 
      anti‑inflammatory purposes in Oriental medicine. Little is known about the effect 
      of Sanggenon C on cardiomyocyte hypoxia injury. This study, using H9c2 rat 
      cardiomyoblasts, was designed to determine the effects of Sanggenon C on 
      cardiomyocyte hypoxia injury. Inflammatory cytokine levels were measured by 
      reverse transcription‑polymerase chain reaction, reactive oxygen species were 
      measured by 2',7'‑dichloro fl uorescin diacetate fluorescent probe, autophagy was 
      detected using the LC3II/I ratio and cell apoptosis was detected by TUNEL 
      staining. The molecular mechanisms underlying Sanggenon C‑induced cyto‑protection 
      were also determined by western blotting, especially the possible involvement of 
      autophagy and AMP‑activated protein kinase (AMPK). Results indicated that samples 
      pretreated with different concentrations of Sanggenon C (1, 10 and 100 microM) 
      reduced the expression levels of pro‑inflammatory cytokines, including tumor 
      necrosis factor alpha, interleukin (IL)‑1 and IL‑6, under hypoxia. The beneficial 
      effects of Sanggenon C were also associated with reduced levels of reactive 
      oxygen species generation and increased levels of antioxidant nitric oxide and 
      superoxide dismutase. Sanggenon C enhanced hypoxia‑induced autophagy as evidenced 
      by the increased expression levels of autophagy‑associated proteins Beclin and 
      autophagy related 5 as well as the decreased the accumulation of p62, and 
      increased the LC3II/I ratio. Sanggenon C also reduced hypoxia‑induced apoptosis 
      as detected by TUNEL staining and the expression of Bcl‑2 proteins. The 
      beneficial effects of Sanggenon C were associated with enhanced activation level 
      of AMPKalpha and suppressed hypoxia‑induced mechanistic target of rapamycin (mTOR) 
      and forkhead box O3a (FOXO3a) phosphorylation. The AMPK inhibitor Compound C 
      (CpC) was used, and the anti‑apoptotic and pro‑autophagy effects of Sanggenon C 
      in response to hypoxia were abolished by CpC. In conclusion, the current study 
      demonstrated that Sanggenon C possessed direct cytoprotective effects against 
      hypoxia injury in cardiac cells via signaling mechanisms involving the activation 
      of AMPK and concomitant inhibition of mTOR and FOXO3a.
FAU - Gu, Yang
AU  - Gu Y
AD  - Department of Cardiology, Huai'an First People's Hospital, Nanjing Medical 
      University, Huai'an, Jiangsu 223300, P.R. China.
FAU - Gao, Lu
AU  - Gao L
AD  - Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, Henan 450052, P.R. China.
FAU - Chen, Yu
AU  - Chen Y
AD  - Department of Cardiology, Huai'an First People's Hospital, Nanjing Medical 
      University, Huai'an, Jiangsu 223300, P.R. China.
FAU - Xu, Zhuo
AU  - Xu Z
AD  - Department of Cardiology, Huai'an First People's Hospital, Nanjing Medical 
      University, Huai'an, Jiangsu 223300, P.R. China.
FAU - Yu, Kun
AU  - Yu K
AD  - Department of Cardiology, Huai'an First People's Hospital, Nanjing Medical 
      University, Huai'an, Jiangsu 223300, P.R. China.
FAU - Zhang, Dongying
AU  - Zhang D
AD  - Department of Cardiology, Huai'an First People's Hospital, Nanjing Medical 
      University, Huai'an, Jiangsu 223300, P.R. China.
FAU - Zhang, Gang
AU  - Zhang G
AD  - Department of Cardiology, Huai'an First People's Hospital, Nanjing Medical 
      University, Huai'an, Jiangsu 223300, P.R. China.
FAU - Zhang, Xiwen
AU  - Zhang X
AD  - Department of Cardiology, Huai'an First People's Hospital, Nanjing Medical 
      University, Huai'an, Jiangsu 223300, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170927
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Antioxidants)
RN  - 0 (Benzofurans)
RN  - 0 (Chromones)
RN  - 0 (Forkhead Box Protein O3)
RN  - 0 (Protective Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 80651-76-9 (sanggenone C)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Apoptosis
MH  - Autophagy/drug effects
MH  - Benzofurans/*pharmacology
MH  - Cell Hypoxia/drug effects
MH  - Chromones/*pharmacology
MH  - Forkhead Box Protein O3/metabolism
MH  - Myocytes, Cardiac/*drug effects/*metabolism
MH  - Oxidative Stress/drug effects
MH  - Protective Agents/*pharmacology
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC5779897
EDAT- 2017/10/07 06:00
MHDA- 2018/06/26 06:00
PMCR- 2017/09/27
CRDT- 2017/10/07 06:00
PHST- 2017/01/09 00:00 [received]
PHST- 2017/08/04 00:00 [accepted]
PHST- 2017/10/07 06:00 [pubmed]
PHST- 2018/06/26 06:00 [medline]
PHST- 2017/10/07 06:00 [entrez]
PHST- 2017/09/27 00:00 [pmc-release]
AID - mmr-16-06-8130 [pii]
AID - 10.3892/mmr.2017.7646 [doi]
PST - ppublish
SO  - Mol Med Rep. 2017 Dec;16(6):8130-8136. doi: 10.3892/mmr.2017.7646. Epub 2017 Sep 
      27.