PMID- 30375049
OWN - NLM
STAT- MEDLINE
DCOM- 20190603
LR  - 20190603
IS  - 1099-1573 (Electronic)
IS  - 0951-418X (Linking)
VI  - 33
IP  - 1
DP  - 2019 Jan
TI  - (+)-Isobicyclogermacrenal and spathulenol from Aristolochia yunnanensis alleviate 
      cardiac fibrosis by inhibiting transforming growth factor beta/small mother against 
      decapentaplegic signaling pathway.
PG  - 214-223
LID - 10.1002/ptr.6219 [doi]
AB  - Cardiac fibrosis contributes to both systolic and diastolic dysfunction in many 
      cardiac pathophysiologic conditions. Antifibrotic therapies are likely to be a 
      crucial strategy in curbing many fibrosis-related cardiac diseases. In our 
      previous study, an ethyl acetate extract of a traditional Chinese medicine 
      Aristolochia yunnanensis Franch. was found to have a therapeutic effect on 
      myocardial fibrosis in vitro and in vivo. However, the exact chemicals and their 
      mechanisms responsible for the activity of the crude extract have not been 
      illustrated yet. In the current study, 10 sesquiterpenoids (1-10) were isolated 
      from the active extract, and their antifibrotic effects were systematically 
      evaluated in transforming growth factor beta 1 (TGFbeta1)-stimulated cardiac 
      fibroblasts and NIH3T3 fibrosis models. (+)-Isobicyclogermacrenal (1) and 
      spathulenol (2) were identified as the main active components, being more potent 
      than the well-known natural antifibrotic agent oxymatrine. Compounds 1 and 2 
      could inhibit the TGFbeta1-induced cardiac fibroblasts proliferation and suppress 
      the expression of the fibrosis biomarkers fibronectin and alpha-smooth muscle actin 
      via down-regulation of their mRNA levels. The mechanism study revealed that 1 and 
      2 could inhibit the phosphorylation of TGFbeta type I receptor, leading to the 
      decrease of the phosphorylation levels of downstream Smad2/3, then consequently 
      blocking the nuclear translocation of Smad2/3 in the TGFbeta/Smad signaling pathway. 
      These findings suggest that 1 and 2 may serve as promising natural leads for the 
      development of anticardiac fibrosis drugs.
CI  - (c) 2018 John Wiley & Sons, Ltd.
FAU - Lou, Lan-Lan
AU  - Lou LL
AD  - School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
FAU - Li, Wei
AU  - Li W
AD  - School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
FAU - Zhou, Bin-Hua
AU  - Zhou BH
AD  - School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
FAU - Chen, Lin
AU  - Chen L
AD  - School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
FAU - Weng, Han-Zhuang
AU  - Weng HZ
AD  - School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
FAU - Zou, Yi-Hong
AU  - Zou YH
AD  - School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
FAU - Tang, Gui-Hua
AU  - Tang GH
AD  - School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
FAU - Bu, Xian-Zhang
AU  - Bu XZ
AD  - School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
FAU - Yin, Sheng
AU  - Yin S
AUID- ORCID: 0000-0002-5678-6634
AD  - School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
LA  - eng
GR  - 2014A030306047/Guangdong Natural Science Funds for Distinguished Young Scholar/
GR  - 17ykzd12/Fundamental Research Funds for the Central Universities/
GR  - 2015A020211007/Science and Technology Planning Project of Guangdong Province, 
      China/
GR  - 81573302/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20181029
PL  - England
TA  - Phytother Res
JT  - Phytotherapy research : PTR
JID - 8904486
RN  - 0 (Aldehydes)
RN  - 0 (Sesquiterpenes)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (isobicyclogermacrenal)
RN  - 7XV9L96SJJ (spathulenol)
SB  - IM
MH  - Aldehydes/pharmacology/*therapeutic use
MH  - Animals
MH  - Aristolochia/*chemistry
MH  - Fibrosis/*drug therapy/pathology
MH  - Humans
MH  - Male
MH  - Medicine, Chinese Traditional/*methods
MH  - Mice
MH  - Mothers
MH  - Rats, Sprague-Dawley
MH  - Sesquiterpenes/pharmacology/*therapeutic use
MH  - Signal Transduction
MH  - Transforming Growth Factor beta/*metabolism
OTO - NOTNLM
OT  - (+)-Isobicyclogermacrenal
OT  - Aristolochia yunnanensis
OT  - TGFbeta/Smad
OT  - cardiac fibrosis
OT  - spathulenol
EDAT- 2018/10/31 06:00
MHDA- 2019/06/04 06:00
CRDT- 2018/10/31 06:00
PHST- 2018/03/28 00:00 [received]
PHST- 2018/09/03 00:00 [revised]
PHST- 2018/09/30 00:00 [accepted]
PHST- 2018/10/31 06:00 [pubmed]
PHST- 2019/06/04 06:00 [medline]
PHST- 2018/10/31 06:00 [entrez]
AID - 10.1002/ptr.6219 [doi]
PST - ppublish
SO  - Phytother Res. 2019 Jan;33(1):214-223. doi: 10.1002/ptr.6219. Epub 2018 Oct 29.