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

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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.

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          Author and article information

          Journal
          Exp Biol Med (Maywood)
          Exp. Biol. Med. (Maywood)
          EBM
          spebm
          Experimental Biology and Medicine
          SAGE Publications (Sage UK: London, England )
          1535-3702
          1535-3699
          April 2015
          April 2015
          : 240
          : 4
          : 508-518
          Affiliations
          [1 ]Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu 706–828, Korea
          [2 ]Department of Pharmacology, Mudanjiang Medical University, Mudanjiang 157011, China
          Author notes
          [*]Dr. Young Woo Kim. Email: ywkim@ 123456dhu.ac.kr , Rong Jie Zhao. Email: zhao_rongjie@ 123456yahoo.com and Sang Chan Kim. Email: sckim@ 123456dhu.ac.kr
          Article
          PMC4935380 PMC4935380 4935380 10.1177_1535370214547123
          10.1177/1535370214547123
          4935380
          25125496
          2cc0c637-05c1-46d9-bda1-374cf4959643
          © 2014 by the Society for Experimental Biology and Medicine
          History
          : 6 February 2014
          : 3 July 2014
          Categories
          Original Research
          Pharmacology/Toxicology

          AMP-activated protein kinase,Honokiol,magnolol,hepatic steatosis,sterol regulatory element binding protein-1 c

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