PMID- 28841738
OWN - NLM
STAT- MEDLINE
DCOM- 20180801
LR  - 20211204
IS  - 1439-0221 (Electronic)
IS  - 0032-0943 (Linking)
VI  - 84
IP  - 2
DP  - 2018 Jan
TI  - Aucubin Protects against TGFbeta1-Induced Cardiac Fibroblasts Activation by 
      Mediating the AMPKalpha/mTOR Signaling Pathway.
PG  - 91-99
LID - 10.1055/s-0043-118663 [doi]
AB  - Fibrosis is a key feature of various cardiovascular diseases and compromises 
      cardiac systolic and diastolic performance. The lack of effective anti-fibrosis 
      drugs is a major contributor to the increasing prevalence of heart failure. The 
      present study was performed to investigate whether the iridoid aucubin alleviates 
      cardiac fibroblast activation and its underlying mechanisms. Neonatal rat cardiac 
      fibroblasts were incubated with aucubin (1, 10, 20, 50 microM) followed by 
      transforming growth factor beta1 (TGFbeta1, 10 ng/mL) stimulation for 24 h. Fibrosis 
      proliferation was measured by cell counting kit-8 assay. The differentiation of 
      fibroblasts into myofibroblasts was determined by measuring the expression of 
      alpha-smooth muscle actin. Then, the expressions levels of cardiac fibrosis-related 
      proteins in myofibroblasts were analyzed by western blot and real-time PCR to 
      confirm the anti-fibrosis effect of aucubin. As a result, aucubin suppressed 
      TGFbeta1-induced proliferation in fibroblasts and inhibited the TGFbeta1-induced 
      activation of fibroblasts to myofibroblasts. In addition, aucubin further 
      attenuated fibrosis-related protein expression in myofibroblasts. Furthermore, 
      this protective effect was related to increased adenosine 
      5'-monophosphate-activated protein kinase (AMPK) phosphorylation and decreased 
      mammalian target of rapamycin (mTOR) phosphorylation, which was confirmed by an 
      mTOR inhibitor (rapamycin), an AMPK agonist (AICAR) and an AMPKalpha inhibitor 
      compound C. Collectively, our findings suggest that aucubin protects against 
      TGFbeta1-induced fibroblast proliferation, activation and function by regulating the 
      AMPKalpha/mTOR signal axis.
CI  - Georg Thieme Verlag KG Stuttgart . New York.
FAU - Xiao, Yang
AU  - Xiao Y
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
FAU - Chang, Wei
AU  - Chang W
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
FAU - Wu, Qing-Qing
AU  - Wu QQ
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
FAU - Jiang, Xiao-Han
AU  - Jiang XH
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
FAU - Duan, Ming-Xia
AU  - Duan MX
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
FAU - Jin, Ya-Ge
AU  - Jin YG
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
FAU - Tang, Qi-Zhu
AU  - Tang QZ
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
LA  - eng
PT  - Journal Article
DEP - 20170825
PL  - Germany
TA  - Planta Med
JT  - Planta medica
JID - 0066751
RN  - 0 (Iridoid Glucosides)
RN  - 0 (Tgfb1 protein, rat)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 2G52GS8UML (aucubin)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
EIN - Planta Med. 2018 Jan;84(2):E2. PMID: 29165727
MH  - AMP-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Animals
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Fibroblasts/*drug effects/metabolism
MH  - Fibrosis/prevention & control
MH  - Heart/drug effects
MH  - Iridoid Glucosides/*pharmacology
MH  - Myocardium/*cytology/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Transforming Growth Factor beta1/*metabolism
COIS- Conflict of Interest: The authors declare that they have no conflicts of interest 
      in the authorship or publication of this contribution.
EDAT- 2017/08/26 06:00
MHDA- 2018/08/02 06:00
CRDT- 2017/08/26 06:00
PHST- 2017/08/26 06:00 [pubmed]
PHST- 2018/08/02 06:00 [medline]
PHST- 2017/08/26 06:00 [entrez]
AID - 10.1055/s-0043-118663 [doi]
PST - ppublish
SO  - Planta Med. 2018 Jan;84(2):91-99. doi: 10.1055/s-0043-118663. Epub 2017 Aug 25.