Acanthoic acid, a diterpene in Acanthopanax koreanum, ameliorates the development of liver fibrosis via LXRs signals.

Abstract

Liver X receptors (LXRs)-mediated signals in acanthoic acid (AA) ameliorating liver fibrosis were examined in carbon tetrachloride (CCl4)-induced mice and TGF-β stimulated hepatic stellate cells (HSCs). AA was isolated from the root of Acanthopanax koreanum Nakai (Araliaceae). CCl4-treated mice were intraperitoneally injected with 10% CCl4 in olive oil (2 mL/kg for 8 weeks). In AA treated groups, mice were intragastrically administrated with AA (20 mg/kg or 50 mg/kg) 3 times per week for 8 weeks. Administration of AA reduced serum aminotransferase and tissue necrosis factor-α (TNF-α) levels evoked by CCl4, and the reverse of liver damage was further confirmed by histopathological staining. Administration of AA reduced the expression of fibrosis markers and regulated the ratio of MMP-13/TIMP-1, further reversed the development of liver fibrosis. TGF-β (5 ng/ml) was added to activate HSC-T6 cells for 2 h, and then treated with AA (1, 3, or 10 μmol/l) for 24 h before analysis. Cells were collected and proteins were extracted to detect the expressions of LXRs. AA could inhibit the expression of α-SMA stimulated by TGF-β and increase the expression of LXRβ. In vivo and in vitro experiments, AA could modulate liver fibrosis induced by CCl4-treatment via activation of LXRα and LXRβ, while inhibit HSCs activation only via activation of LXRβ. Acanthoic acid might ameliorate liver fibrosis induced by CCl4 via LXRs signals.

• Authors: Ting Bai, You-li Yao, Xue-jun Jin, Li-hua Lian, Qian Li, Ning Yang, Quan Jin, Yan-ling Wu, Ji-xing Nan
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 218 Pg. 63-70 (Jul 25 2014) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 24802811 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Diterpenes
• Liver X Receptors
• Nr1h3 protein, mouse
• Orphan Nuclear Receptors
• Plant Extracts
• acanthoic acid
• Carbon Tetrachloride

Topics

• Animals
• Carbon Tetrachloride
• Cells, Cultured
• Diterpenes (chemistry, pharmacology)
• Eleutherococcus (chemistry)
• Liver Cirrhosis (chemically induced, prevention & control)
• Liver X Receptors
• Male
• Mice
• Mice, Inbred C57BL
• Orphan Nuclear Receptors (metabolism)
• Plant Extracts (pharmacology)
• Signal Transduction (drug effects)