PMID- 26660048
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20210109
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 173
IP  - 6
DP  - 2016 Mar
TI  - Genipin alleviates sepsis-induced liver injury by restoring autophagy.
PG  - 980-91
LID - 10.1111/bph.13397 [doi]
AB  - BACKGROUND AND PURPOSE: Autophagy is an essential cytoprotective system that is 
      rapidly activated in response to various stimuli including inflammation and 
      microbial infection. Genipin, an aglycon of geniposide found in gardenia fruit, 
      is well known to have anti-inflammatory, antibacterial and antioxidative 
      properties. This study examined the protective mechanisms of genipin against 
      sepsis, with particular focus on the autophagic signalling pathway. EXPERIMENTAL 
      APPROACH: Mice were subjected to sepsis by caecal ligation and puncture (CLP). 
      Genipin (1, 2.5 and 5 mg.kg(-1) ) or vehicle (saline) was injected i.v. 
      immediately (0 h) after CLP, and chloroquine (60 mg.kg(-1) ), an autophagy 
      inhibitor, was injected i.p. 1 h before CLP. Blood and liver tissues were 
      isolated 6 h after CLP. KEY RESULTS: Genipin improved survival rate and decreased 
      serum levels of aminotransferases and pro-inflammatory cytokines after CLP; 
      effects abolished by chloroquine. The liver expression of autophagy-related 
      protein (Atg)12-Atg5 conjugate increased after CLP, and this increase was 
      enhanced by genipin. CLP decreased Atg3 protein liver expression, and genipin 
      attenuated this decrease. CLP impaired autophagic flux, as indicated by increased 
      liver expression of microtubule-associated protein-1 light chain 3-II and 
      sequestosome-1/p62 protein; this impaired autophagic flux was restored by 
      genipin, and chloroquine abolished this effect. Genipin also attenuated the 
      decreased expression of lysosome-associated membrane protein-2 and Rab7 protein 
      and increased expression of calpain 1 protein induced by CLP in the liver. 
      CONCLUSIONS AND IMPLICATIONS: Our findings suggest that genipin protects against 
      septic injury by restoring impaired autophagic flux. Therefore, genipin might be 
      a potential therapeutic agent for the treatment of sepsis.
CI  - (c) 2015 The British Pharmacological Society.
FAU - Cho, Hong-Ik
AU  - Cho HI
AD  - School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, South Korea.
FAU - Kim, So-Jin
AU  - Kim SJ
AD  - School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, South Korea.
FAU - Choi, Joo-Wan
AU  - Choi JW
AD  - School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, South Korea.
FAU - Lee, Sun-Mee
AU  - Lee SM
AD  - School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, South Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160210
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Autophagy-Related Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (Iridoids)
RN  - 0 (Protective Agents)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (interleukin-6, mouse)
RN  - 886U3H6UFF (Chloroquine)
RN  - A3V2NE52YG (genipin)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Aspartate Aminotransferases/blood
MH  - Autophagy/*drug effects
MH  - Autophagy-Related Proteins/metabolism
MH  - Chloroquine/pharmacology
MH  - Interleukin-6/blood
MH  - Iridoids/pharmacology/*therapeutic use
MH  - Liver/drug effects/metabolism/ultrastructure
MH  - Liver Diseases/blood/*drug therapy/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Microscopy, Electron, Transmission
MH  - Protective Agents/pharmacology/*therapeutic use
MH  - Sepsis/blood/complications/*drug therapy/metabolism
MH  - Tumor Necrosis Factor-alpha/blood
PMC - PMC5341236
EDAT- 2015/12/15 06:00
MHDA- 2016/12/15 06:00
PMCR- 2017/03/01
CRDT- 2015/12/15 06:00
PHST- 2015/10/10 00:00 [received]
PHST- 2015/11/18 00:00 [revised]
PHST- 2015/11/30 00:00 [accepted]
PHST- 2015/12/15 06:00 [entrez]
PHST- 2015/12/15 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
PHST- 2017/03/01 00:00 [pmc-release]
AID - BPH13397 [pii]
AID - 10.1111/bph.13397 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2016 Mar;173(6):980-91. doi: 10.1111/bph.13397. Epub 2016 Feb 10.