title: Cynanchum wilfordii Radix attenuates liver fat accumulation and damage by suppressing hepatic cyclooxygenase-2 and mitogen-activated protein kinase in mice fed with a high-fat and high-fructose diet.
abstract: Excessive consumption of fat and fructose augments the pathological progression of nonalcoholic fatty liver disease through hepatic fibrosis, inflammation, and hepatic de novo lipogenesis. We hypothesized that supplementation with Cynanchum wilfordii extract (CWE) decreases fat accumulation in the liver by suppressing cyclooxygenase-2 (COX-2), the nuclear translocation of nuclear factor κB (NF-κB), and p38 mitogen-activated protein kinase (MAPK). The beneficial effect of CWE was evaluated in a murine model of nonalcoholic fatty liver disease. Mice were fed either a normal diet or an atherogenic diet with fructose (ATHFR) in the presence or absence of CWE (50, 100, or 200 mg/kg; n=6/group). Treatment with ATHFR induced a hepatosplenomegaly-like condition (increased liver and spleen weight); this pathological change was attenuated in the presence of CWE. The ATHFR group exhibited impaired liver function, as evidenced by increased blood levels of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, fat accumulation in the liver, and lipid profiles. Supplementation of CWE (100 and 200 mg/kg, P<.05) ameliorated these impaired liver functions. Atherogenic diet with fructose increased the protein levels of COX-2 and p38 MAPK, as well as the nuclear translocation of NF-κB. These signaling pathways, which are associated with the inflammatory response, were markedly suppressed after CWE treatment (100 and 200 mg/kg). In summary, CWE supplementation reduced high-fat and high-fructose diet-induced fat accumulation and damage in the liver by suppressing COX-2, NF-κB, and p38 MAPK.
authors.affiliation: Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, Korea.
authors.forename: Seon-A
authors.initials: SA
authors.lastname: Jang
authors.affiliation: College of Medicine, Cardiovascular and Metabolic Disease Center and Department of Health Sciences and Technology, Graduate School of Inje University, Inje University, Busan 614-735, Korea.
authors.forename: SungRyul
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Herbal Medicine Resources, Kangwon National University, Samcheok 245-710, Korea.
authors.forename: Eun-Hwa
authors.initials: EH
authors.lastname: Sohn
authors.affiliation: Department of Medicinal and Industrial Crops, Korea National College of Agriculture and Fisheries, Jeonju 54874, Korea.
authors.forename: Jaehyuk
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Park
authors.affiliation: Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, Korea.
authors.forename: Yong Joon
authors.initials: YJ
authors.lastname: Jeong
authors.affiliation: Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, Korea.
authors.forename: Inhye
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, Korea.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Kwon
authors.affiliation: Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, Korea.
authors.forename: Hae Seong
authors.initials: HS
authors.lastname: Song
authors.affiliation: Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, Korea.
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Cho
authors.affiliation: Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, Korea.
authors.forename: Xue
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Medicinal and Industrial Crops, Korea National College of Agriculture and Fisheries, Jeonju 54874, Korea. Electronic address: hjungkoo@korea.kr.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Koo
authors.affiliation: Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, Korea. Electronic address: sckang@khu.ac.kr.
authors.forename: Se Chan
authors.initials: SC
authors.lastname: Kang
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D031105:Cynanchum; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D000073417:Dietary Sugars / Q000008:administration & dosage / Q000009:adverse effects; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005247:Feeding Behavior; D005632:Fructose / Q000009:adverse effects*; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000517:prevention & control*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D018517:Plant Roots; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D004041:Dietary Fats; D000073417:Dietary Sugars; D016328:NF-kappa B; D010936:Plant Extracts; D005632:Fructose; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Cyclooxygenase-2; Cynanchum wilfordii; Hepatic inflammation; Nonalcoholic fatty liver disease; Nuclear factor κB; p38 MAPK