title: Gastrodin Ameliorates Oxidative Stress and Proinflammatory Response in Nonalcoholic Fatty Liver Disease through the AMPK/Nrf2 Pathway.
abstract: This study was designed to investigate the antioxidative, antiinflammatory and metabolism-regulating effects of gastrodin (GSTD) in the treatment of nonalcoholic fatty liver disease (NAFLD). Oleic acid (OA) was used to induce steatosis in HL-7702 cells; a high-fat or high-fat and high-cholesterol diet was used to induce NAFLD in mice and rats. Our results showed that GSTD significantly increased hepatic superoxide dismutase (SOD) but decreased reactive oxygen species (ROS)/malondialdehyde (MDA) and reduced the mRNA levels of proinflammatory cytokines both in vitro and in vivo. GSTD promoted the phosphorylation of nuclear factor erythroid-2-related factor-2 (Nrf2) at serine (Ser) 40, stimulated its nuclear translocation and increased hepatic expression of heme oxygenase-1 (HO-1). GSTD activated AMP-activated protein kinase (AMPK), suppressed hepatic steatosis, lowered serum triglyceride (TG)/glucose and decreased body weight gain in animals with NAFLD. The stimulating effects of GSTD on the Nrf2 pathway as well as its antioxidative/antiinflammatory activities were abolished by compound C in OA-treated HL-7702 cells. In summary, our results demonstrate that GSTD activates the AMPK/Nrf2 pathway, ameliorates oxidative stress/proinflammatory response and improves lipid metabolism in NAFLD. Our findings may support the future clinical application of GSTD for the treatment of NAFLD to reduce hepatic steatosis, oxidative stress and proinflammatory response.
authors.affiliation: State Key Laboratory of Bioactive Natural Products and Function, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Qu
authors.affiliation: Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Microbiology and Molecular Genetics, Emory University, Atlanta, GA, USA.
authors.forename: Wen-Xiao
authors.initials: WX
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Bioactive Natural Products and Function, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Wei-Jia
authors.initials: WJ
authors.lastname: Kong
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001592:Benzyl Alcohols / Q000494:pharmacology / Q000627:therapeutic use*; D031668:Gastrodia / Q000737:chemistry*; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001592:Benzyl Alcohols; D005960:Glucosides; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D014280:Triglycerides; D008315:Malondialdehyde; C045345:gastrodin; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; Nrf2; gastrodin; hepatic steatosis; proinflammatory cytokines