Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Licochalcone Suppresses LXRα-Induced Hepatic Lipogenic Gene Expression through AMPK/Sirt1 Pathway Activation

  • Han, Jae Yun (College of Pharmacy, Chosun University) ;
  • Park, Sun Hee (College of Pharmacy, Chosun University) ;
  • Yang, Ji Hye (College of Pharmacy, Chosun University) ;
  • Kim, Mi Gwang (College of Pharmacy, Chosun University) ;
  • Cho, Seung Sik (College of Pharmacy, Mokpo National University) ;
  • Yoon, Goo (College of Pharmacy, Mokpo National University) ;
  • Cheon, Seung Hoon (College of Pharmacy and Research Institute of Drug Development, Chonnam National University) ;
  • Ki, Sung Hwan (College of Pharmacy, Chosun University)
  • Received : 2014.02.27
  • Accepted : 2014.03.26
  • Published : 2014.03.31
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Abstract

Licochalcone (LC), a major phenolic retrochalcone from licorice, has anti-inflammatory activity. This study investigated the effects of licochalcone A (LCA) and licochalcone E (LCE) on Liver X receptor-${\alpha}$ ($LXR{\alpha}$)-mediated lipogenic gene expression and the molecular mechanisms underlying those effects. LCA and LCE antagonized the ability of $LXR{\alpha}$ agonists (T0901317 or GW3965) to increase sterol regulatory element binding protein-1c (SREBP-1c) expression and thereby inhibited target gene expression (e.g., FAS and ACC) in HepG2 cells. Moreover, treatment with LCA and LCE impaired $LXR{\alpha}/RXR{\alpha}$-induced CYP7A1-LXRE-luciferase (CYP7A1) transactivation. The AMPK-Sirt1 signaling pathway is an important regulator of energy metabolism and, therefore, a potential therapeutic target for metabolic diseases, including hepatic steatosis. We found here that LCE increased AMPK phosphorylation and Sirt1 expression. We conclude that LC inhibits SREBP-1c-mediated hepatic lipogenesis via activation of the AMPK/Sirt1 signaling pathway.

Keywords

References

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