Efficacy of sauchinone as a novel AMPK-activating lignan for preventing iron-induced oxidative stress and liver injury.
- Efficacy of sauchinone as a novel AMPK-activating lignan for preventing iron-induced oxidative stress and liver injury.
- 김영우; 이성민; 신상미; 황세진; Janie S. Brooks; 강희은; 이명걸; 김상찬; 김상건
- Iron-induced liver injury; Sauchinone; AMPK; Oxidative stress; Arachidonic acid; Free radicals
- Issue Date
- Free radical biology & medicine
- VOL 47, NO 7, 1082-1092
- Iron-overload disorders cause hepatocyte injury and inflammation by oxidative stress, possibly leading to liver
fibrosis and hepatocellular carcinoma. This study investigated the efficacy of sauchinone, a bioactive lignan, in
preventing iron-induced liver injury and explored the mechanism of sauchinone's activity. To create iron
overload, mice were injected with phenylhydrazine, and the effects on hepatic iron and histopathology were
assessed. Phenylhydrazine treatment promoted liver iron accumulation and ferritin expression, causing
hepatocyte death and increased plasma arachidonic acid (AA). Sauchinone attenuated liver injury
(EC50=10 mg/kg) and activated AMPK in mice. Treatment of hepatocytes with iron and AA simulated iron
overload conditions: iron + AA synergistically amplified cytotoxicity, increasing H2O2 and the mitochondrial
permeability transition. Sauchinone protected hepatocytes from iron + AA-induced cytotoxicity, preventing
the induction of mitochondrial dysfunction and apoptosis (EC50=1μM), similar to the result using metformin.
Sauchinone treatment activated LKB1, which led to AMPK activation: these events contributed to cell survival.
Evidence of cytoprotection by LKB1 and AMPK activation was revealed in the reversal of sauchinone's
restoration of the mitochondrial membrane potential by either dominant negative mutant AMPKα or chemical
inhibitor. In conclusion, sauchinone protects the liver from toxicity induced by iron accumulation, and
sauchinone's effects may be mediated by LKB1-dependent AMPK activation.
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