PMID- 31296386
OWN - NLM
STAT- MEDLINE
DCOM- 20200601
LR  - 20200601
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 516
IP  - 4
DP  - 2019 Sep 3
TI  - Deoxyelephantopin suppresses hepatic stellate cells activation associated with 
      inhibition of aerobic glycolysis via hedgehog pathway.
PG  - 1222-1228
LID - S0006-291X(19)31345-2 [pii]
LID - 10.1016/j.bbrc.2019.07.015 [doi]
AB  - Accumulating evidence suggests that hepatic stellate cells (HSCs) adopt aerobic 
      glycolysis during activation. Hedgehog (Hh) pathway plays a vital role in the 
      process of HSCs activation by regulating metabolism, and activation of the Hh 
      pathway promotes transdifferentiation of HSCs into myofibroblasts. 
      Deoxyelephantopin (DET), a naturally occurring sesquiterpene lactone from 
      Elephantopus scaber, has been shown to exert hepatoprotective as well as 
      anticancer effects. However, the effect of DET on hepatic fibrosis and glycolysis 
      in HSCs have never been elucidated. Here, we studied the function of the DET on 
      HSCs activation and investigated the anti-fibrogenic effects of DET was 
      associated with interfering with glycolysis in HSCs. Our results first 
      demonstrated that DET reduced the expression of a-smooth muscle actin (a-SMA) and 
      a1(I)procollagen at both mRNA and protein levels, and restore lipogenesis in 
      HSCs. Furthermore, DET decreased the expression of hexokinase (HK), 
      phosphofructokinase-2 (PFK2), Glucose transporter 4 (Glut4), and reduced lactate 
      production dose-dependently in HSCs. Moreover, we further revealed that DET 
      reduced fibrotic gene expression, restored lipid accumulation in HSCs. However, 
      the Hh pathway agonist SAG could reverse the above effect of DET. Together, these 
      results indicate DET inhibits aerobic glycolysis in HSCs associated with 
      inhibition of Hh pathway. Our results provided a novel mechanism for DET 
      suppression of HSC activation implicated in antifibrotic therapy.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Gao, Wei
AU  - Gao W
AD  - School of Nursing, Jiangsu Vocational College of Medicine, Yancheng, China.
FAU - Sun, Jing
AU  - Sun J
AD  - School of Nursing, Jiangsu Vocational College of Medicine, Yancheng, China.
FAU - Wang, Feng
AU  - Wang F
AD  - School of Nursing, Jiangsu Vocational College of Medicine, Yancheng, China.
FAU - Lu, Yuxian
AU  - Lu Y
AD  - School of Nursing, Jiangsu Vocational College of Medicine, Yancheng, China.
FAU - Wen, Chun
AU  - Wen C
AD  - School of Nursing, Jiangsu Vocational College of Medicine, Yancheng, China.
FAU - Bian, Qingya
AU  - Bian Q
AD  - School of Pharmacy, Jiangsu Vocational College of Medicine, Yancheng, China.
FAU - Wu, Hongyan
AU  - Wu H
AD  - Institute of Biomedical Technology, Jiangsu Vocational College of Medicine, 
      Yancheng, China; Department of Pharmacology, School of Basic Medical Sciences, 
      Nanjing Medical University, Nanjing, China. Electronic address: 
      Why20133055@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190709
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Lactones)
RN  - 0 (Protective Agents)
RN  - 0 (Sesquiterpenes)
RN  - 0 (deoxyelephantopin)
SB  - IM
MH  - Animals
MH  - Asteraceae/chemistry
MH  - Cell Line
MH  - Glycolysis/drug effects
MH  - Hedgehog Proteins/*metabolism
MH  - Hepatic Stellate Cells/*drug effects/metabolism
MH  - Lactones/chemistry/*pharmacology
MH  - Lipogenesis/drug effects
MH  - Liver Cirrhosis/drug therapy/metabolism
MH  - Protective Agents/chemistry/*pharmacology
MH  - Rats
MH  - Sesquiterpenes/chemistry/*pharmacology
MH  - Signal Transduction/*drug effects
OTO - NOTNLM
OT  - Aerobic glycolysis
OT  - Deoxyelephantopin (DET)
OT  - Hedgehog (Hh) pathway
OT  - Hepatic stellate cell
OT  - Liver fibrosis
EDAT- 2019/07/13 06:00
MHDA- 2020/06/02 06:00
CRDT- 2019/07/13 06:00
PHST- 2019/06/30 00:00 [received]
PHST- 2019/07/05 00:00 [accepted]
PHST- 2019/07/13 06:00 [pubmed]
PHST- 2020/06/02 06:00 [medline]
PHST- 2019/07/13 06:00 [entrez]
AID - S0006-291X(19)31345-2 [pii]
AID - 10.1016/j.bbrc.2019.07.015 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Sep 3;516(4):1222-1228. doi: 
      10.1016/j.bbrc.2019.07.015. Epub 2019 Jul 9.