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The AMPK activation by sauchinone, a Saururus chinensis lignan, enables hepatocytes to protect against the toxicity induced by iron overload
Author(s) -
Shin Sang Mi,
Kim Young Woo,
Kim Sang Geon
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.581.11
Subject(s) - chemistry , ampk , pharmacology , lignan , liver injury , reactive oxygen species , biochemistry , medicine , phosphorylation , stereochemistry , protein kinase a
Iron overload disorder may lead to liver fibrosis and hepatocellular carcinoma. Sauchinone, a lignan in Saururus chinensis, inhibits the induction of iNOS and TNF‐alpha in macrophages. This study investigated the hepatoprotective effect of sauchinone in mice challenged with phenylhydrazine (PHZ), an in vivo model representing hepatic iron overload. PHZ treatments that elevated iron and arachidonic acid (AA, a proinflammatory lipid) levels in plasma caused liver injury, which was attenuated by concomitant sauchinone treatments. The molecular basis of sauchinone′s hepatoprotective effect was explored in a hepatocyte model. Combination treatment of iron and AA synergistically increased cytotoxicity, as supported by increases in reactive oxygen species, mitochondrial dysfunction and apoptosis, all of which were prevented by sauchinone. Sauchinone activated AMPK via LKB1, which was responsible for its cytoprotective effect, as shown by an experiment using a dominant negative mutant construct. AMPK activation by sauchinone was confirmed in the mouse liver. These results demonstrated that sauchinone enables hepatocytes to protect against iron‐induced toxicity, which might be associated with its AMPK activation.