Combination of honokiol and magnolol inhibits hepatic steatosis through AMPK-SREBP-1 c pathway

被引：48

作者：

Lee, Ju-Hee ^{[1
]}

Jung, Ji Yun ^{[1
]}

Jang, Eun Jeong ^{[1
]}

Jegal, Kyung Hwan ^{[1
]}

Moon, Soo Young ^{[1
]}

Ku, Sae Kwang ^{[1
]}

Kang, Seung Ho ^{[1
]}

Cho, Il Je ^{[1
]}

Park, Sook Jahr ^{[1
]}

Lee, Jong Rok ^{[1
]}

Zhao, Rong Jie ^{[1
,2
]}

Kim, Sang Chan ^{[1
]}

Kim, Young Woo ^{[1
]}

机构：

[1] Daegu Haany Univ, Coll Oriental Med, Med Res Ctr Globalizat Herbal Formulat, Daegu 706828, South Korea

[2] Mudanjiang Med Univ, Dept Pharmacol, Mudanjiang 157011, Peoples R China

来源：

EXPERIMENTAL BIOLOGY AND MEDICINE | 2015年 / 240卷 / 04期

基金：

新加坡国家研究基金会;

关键词：

Honokiol; magnolol; hepatic steatosis; sterol regulatory element binding protein-1 c; AMP-activated protein kinase; NONALCOHOLIC FATTY LIVER; ACTIVATED PROTEIN-KINASE; ELEMENT-BINDING PROTEIN-1C; METABOLIC SYNDROME; INSULIN-RESISTANCE; STEROL REGULATION; MOUSE MODEL; OFFICINALIS; MICE; ACID;

D O I：

10.1177/1535370214547123

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Honokiol and magnolol, as pharmacological biphenolic compounds of Magnolia officinalis, have been reported to have antioxidant and anti-inflammatory properties. Sterol regulatory element binding protein-1 c (SREBP-1 c) plays an important role in the development and processing of steatosis in the liver. In the present study, we investigated the effects of a combination of honokiol and magnolol on SREBP-1 c-dependent lipogenesis in hepatocytes as well as in mice with fatty liver due to consumption of high-fat diet (HFD). Liver X receptor alpha (LXR alpha) agonists induced activation of SREBP-1 c and expression of lipogenic genes, which were blocked by co-treatment of honokiol and magnolol (HM). Moreover, a combination of HM potently increased mRNA of fatty acid oxidation genes. HM induced AMP-activated protein kinase (AMPK), an inhibitory kinase of the LXR alpha-SREBP-1 c pathway. The role of AMPK activation induced by HM was confirmed using an inhibitor of AMPK, Compound C, which reversed the ability of HM to both inhibit SREBP-1 c induction as well as induce genes for fatty acid oxidation. In mice, HM administration for four weeks ameliorated HFD-induced hepatic steatosis and liver dysfunction, as indicated by plasma parameters and Oil Red O staining. Taken together, our results demonstrated that a combination of HM has beneficial effects on inhibition of fatty liver and SREBP-1 c-mediated hepatic lipogenesis, and these events may be mediated by AMPK activation.

引用

页码：508 / 518

页数：11

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[1] Modulation of sterol regulatory element binding proteins (SREBPs) as potential treatments for non-alcoholic fatty liver disease (NAFLD) [J].