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

Ju-Hee Lee, Ji Yun Jung, Eun Jeong Jang, Kyung Hwan Jegal, Soo Young Moon, Sae Kwang Ku, Seung Ho Kang, Il Je Cho, Sook Jahr Park, Jong Rok Lee, Rong Jie Zhao, Sang Chan Kim, Young Woo Kim

Index: Exp. Biol. Med. (Maywood.) 240(4) , 508-18, (2015)

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Abstract

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 α (LXRα) 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 LXRα-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.© 2014 by the Society for Experimental Biology and Medicine.