title: Combination of honokiol and magnolol inhibits hepatic steatosis through AMPK-SREBP-1 c pathway.
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.
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Korea.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Jang
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Korea.
authors.forename: Kyung Hwan
authors.initials: KH
authors.lastname: Jegal
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Moon
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Korea.
authors.forename: Sae Kwang
authors.initials: SK
authors.lastname: Ku
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Korea.
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Kang
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Korea.
authors.forename: Il Je
authors.initials: IJ
authors.lastname: Cho
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Korea.
authors.forename: Sook Jahr
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Korea.
authors.forename: Jong Rok
authors.initials: JR
authors.lastname: Lee
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Korea Department of Pharmacology, Mudanjiang Medical University, Mudanjiang 157011, China.
authors.forename: Rong Jie
authors.initials: RJ
authors.lastname: Zhao
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Korea.
authors.forename: Sang Chan
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Medical Research Center for Globalization of Herbal Formulation, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Korea ywkim@dhu.ac.kr zhao_rongjie@yahoo.com sckim@dhu.ac.kr.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005234:Fatty Liver / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D006801:Humans; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use*; D050155:Lipogenesis / Q000187:drug effects / Q000502:physiology; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000502:physiology*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D055372:AMP-Activated Protein Kinases; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D017705:Lignans; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D051780:Sterol Regulatory Element Binding Protein 1; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; C005498:magnolol; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: AMP-activated protein kinase; Honokiol; hepatic steatosis; magnolol; sterol regulatory element binding protein-1 c