PMID- 27135544
OWN - NLM
STAT- MEDLINE
DCOM- 20170327
LR  - 20170805
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 36
DP  - 2016 Jul
TI  - Dioscin reduces lipopolysaccharide-induced inflammatory liver injury via 
      regulating TLR4/MyD88 signal pathway.
PG  - 132-141
LID - S1567-5769(16)30157-6 [pii]
LID - 10.1016/j.intimp.2016.04.023 [doi]
AB  - We previously reported the effects of dioscin against carbon tetrachloride-, 
      acetaminophen- and alcohol-induced acute liver damage. However, its effect on 
      lipopolysaccharide (LPS)-induced inflammatory liver injury remains unknown. In 
      the present work, liver injury in mice and rats was induced by LPS, and dioscin 
      was intragastrically administered for 7days. In vitro, the AML-12 cells and 
      HepG-2 cells were treated with LPS after dioscin treatment. The results showed 
      that dioscin not only markedly reduced serum ALT, AST levels and relative liver 
      weights, but also restored cell injury caused by LPS. In mechanism study, dioscin 
      significantly attenuated inflammation through down-regulating the levels of 
      toll-like receptor (TLR) 4, myeloid differentiation factor 88 (MyD88), 
      interleukin-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor 
      receptor-associated factor 6 (TRAF6), phosphorylated inhibitor of nuclear factor 
      kappaB kinase (p-IKK), phosphorylated inhibitor of nuclear factor kappaB alpha (p-IkappaBalpha), 
      phosphorylated nuclear factor kappaB p65 (p-NF-kappaB p65), high-mobility group protein 1 
      (HMGB-1), interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-alpha). TLR4 
      overexpression was also decreased by dioscin, leading to the markedly decreased 
      levels of MyD88, IRAK1, TRAF6, p-IKK, p-IkappaBalpha, p-NF-kappaB p65 and HMGB-1. Suppression 
      of MyD88 by ST2825 eliminated the inhibitory effects of dioscin on the levels of 
      IRAK1, TRAF6, p-IKK, p-IkappaBalpha, p-NF-kappaB p65, HMGB-1, IL-1beta, IL-6 and TNF-alpha. Our 
      results suggested that dioscin exhibited protective effect against LPS-induced 
      liver injury via altering TLR4/MyD88 pathway, which should be developed as one 
      potent candidate for the treatment of acute inflammatory liver injury in the 
      future.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Yao, Hong
AU  - Yao H
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Hu, Changsheng
AU  - Hu C
AD  - Huanggang Polytechnic College, No. 109 Taoyuan St., Nanhu Educational District, 
      Huanggang City 438002, Hubei Province, China.
FAU - Yin, Lianhong
AU  - Yin L
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Tao, Xufeng
AU  - Tao X
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Xu, Lina
AU  - Xu L
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Qi, Yan
AU  - Qi Y
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Han, Xu
AU  - Han X
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Xu, Youwei
AU  - Xu Y
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Zhao, Yanyan
AU  - Zhao Y
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Wang, Changyuan
AU  - Wang C
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China.
FAU - Peng, Jinyong
AU  - Peng J
AD  - College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 
      116044, China. Electronic address: jinyongpeng2008@126.com.
LA  - eng
PT  - Journal Article
DEP - 20160429
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Toll-Like Receptor 4)
RN  - 3B95U4OLWV (dioscin)
RN  - K49P2K8WLX (Diosgenin)
SB  - IM
EIN - Int Immunopharmacol. 2019 Sep;74:105786. PMID: 31402320
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Chemical and Drug Induced Liver Injury/*drug therapy
MH  - Cytokines/metabolism
MH  - Dioscorea/*immunology
MH  - Diosgenin/*analogs & derivatives/therapeutic use
MH  - Hep G2 Cells
MH  - Humans
MH  - Lipopolysaccharides/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid Differentiation Factor 88/*metabolism
MH  - NF-kappa B/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/drug effects
MH  - Toll-Like Receptor 4/*metabolism
OTO - NOTNLM
OT  - Acute liver injury
OT  - Dioscin
OT  - Inflammation
OT  - Lipopolysaccharide
OT  - TLR4/MyD88 signal pathway
EDAT- 2016/05/03 06:00
MHDA- 2017/03/28 06:00
CRDT- 2016/05/03 06:00
PHST- 2016/01/17 00:00 [received]
PHST- 2016/03/30 00:00 [revised]
PHST- 2016/04/18 00:00 [accepted]
PHST- 2016/05/03 06:00 [entrez]
PHST- 2016/05/03 06:00 [pubmed]
PHST- 2017/03/28 06:00 [medline]
AID - S1567-5769(16)30157-6 [pii]
AID - 10.1016/j.intimp.2016.04.023 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2016 Jul;36:132-141. doi: 10.1016/j.intimp.2016.04.023. Epub 
      2016 Apr 29.