PMID- 25937827
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150504
LR  - 20201001
IS  - 1749-8546 (Print)
IS  - 1749-8546 (Electronic)
IS  - 1749-8546 (Linking)
VI  - 10
DP  - 2015
TI  - Selective inhibition of liver X receptor alpha-mediated lipogenesis in primary 
      hepatocytes by licochalcone A.
PG  - 8
LID - 10.1186/s13020-015-0037-x [doi]
LID - 8
AB  - BACKGROUND: Sterol regulatory element binding protein-1c (SREBP-1c) is a 
      regulator of the lipogenic pathway and is transcriptionally activated by liver X 
      receptor alpha (LXRalpha). This study aims to investigate phytochemicals inhibiting the 
      autonomous transactivity of LXRalpha with potentials as SREBP-1c inhibitors. 
      Licochalcone A (LicA) is a flavonoid isolated from licorice root of Glycyrrhiza 
      plant. METHODS: The effects of 238 natural chemicals on autonomous transactivity 
      of LXRalpha were determined by the Gal4-TK-luciferase reporter system. The inclusion 
      criteria for chemical selection was significant (P < 0.05) inhibition of 
      autonomous transactivity of LXRalpha from three independent experiments. Transcript 
      levels of mouse primary hepatocytes were measured by conventional or quantitative 
      RT-PCR. Luciferase assay was used to assess synthetic or natural promoter 
      activities of LXRalpha target genes. The effect of LicA on lipogenic activity was 
      evaluated by measuring cellular triglycerides in mouse primary hepatocytes. The 
      recruitment of RNA polymerase II to the LXR response element (LXRE) region was 
      examined by chromatin immunoprecipitation. RESULTS: Among 238 natural compounds, 
      LicA considerably inhibited the autonomous transactivity of LXRalpha and decreased 
      the LXRalpha-dependent expression of SREBP-1c. LicA inhibited not only LXRalpha-dependent 
      activation of the synthetic LXRE promoter but also that of the natural SREBP-1c 
      promoter. As a consequence, LicA reduced the LXRalpha agonist-stimulated 
      transcription of several lipogenic genes. Furthermore, LXRalpha-dependent hepatic 
      lipid accumulation was repressed by LicA in mouse primary hepatocytes. 
      Interestingly, the LXRalpha-dependent activation of ATP-binding cassette transporter 
      A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1), other LXR target 
      genes involved in reverse cholesterol transport (RCT), was not inhibited by LicA. 
      LicA hindered the recruitment of RNA polymerase II to the LXRE of the SREBP-1c 
      gene, but not of the ABCA1 gene. CONCLUSIONS: LicA is a selective inhibitor of 
      LXRalpha, repressing lipogenic LXRalpha target genes but not RCT-related LXRalpha target 
      genes.
FAU - Oh, Gyun-Sik
AU  - Oh GS
AD  - Department of Pharmacology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, 138-736 Korea ; Bio-medical Institute of Technology, University 
      of Ulsan College of Medicine, Seoul, 138-736 Korea.
FAU - Lee, Gang Gu
AU  - Lee GG
AD  - Department of Pharmacology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, 138-736 Korea ; Bio-medical Institute of Technology, University 
      of Ulsan College of Medicine, Seoul, 138-736 Korea.
FAU - Yoon, Jin
AU  - Yoon J
AD  - Department of Pharmacology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, 138-736 Korea ; Bio-medical Institute of Technology, University 
      of Ulsan College of Medicine, Seoul, 138-736 Korea.
FAU - Oh, Won Keun
AU  - Oh WK
AD  - Korea Bioactive Natural Material Bank, College of Pharmacy, Seoul National 
      University, Seoul, 151-742 Korea.
FAU - Kim, Seung-Whan
AU  - Kim SW
AD  - Department of Pharmacology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, 138-736 Korea ; Bio-medical Institute of Technology, University 
      of Ulsan College of Medicine, Seoul, 138-736 Korea.
LA  - eng
PT  - Journal Article
DEP - 20150421
PL  - England
TA  - Chin Med
JT  - Chinese medicine
JID - 101265109
PMC - PMC4416341
EDAT- 2015/05/06 06:00
MHDA- 2015/05/06 06:01
PMCR- 2015/04/21
CRDT- 2015/05/05 06:00
PHST- 2014/09/19 00:00 [received]
PHST- 2015/04/13 00:00 [accepted]
PHST- 2015/05/05 06:00 [entrez]
PHST- 2015/05/06 06:00 [pubmed]
PHST- 2015/05/06 06:01 [medline]
PHST- 2015/04/21 00:00 [pmc-release]
AID - 37 [pii]
AID - 10.1186/s13020-015-0037-x [doi]
PST - epublish
SO  - Chin Med. 2015 Apr 21;10:8. doi: 10.1186/s13020-015-0037-x. eCollection 2015.