title: Nandinine, a Derivative of Berberine, Inhibits Inflammation and Reduces Insulin Resistance in Adipocytes via Regulation of AMP-Kinase Activity.
abstract: Nandinine is a derivative of berberine that has high efficacy for treating cardiovascular diseases. This study investigated the effects of berberine and nandinine on the regulation of insulin sensitivity in adipocytes. Through treatment with macrophage-derived conditioned medium in 3T3-L1 adipocytes, dysregulation of adipokine production and activation of the IκB kinaseβ/nuclear factor-kappa B pathway was induced. However, these phenomena were effectively reversed by berberine, nandinine, and salicylate pretreatments. Furthermore, both berberine and nandinine inhibited serine phosphorylation of insulin receptor substrate-1 induced by IκB kinaseβand increased tyrosine phosphorylation of insulin receptor substrate-1 to activate the PI3K/Akt pathway, which finally led to insulin-mediated glucose uptake. In addition, berberine and nandinine significantly increased AMP-activated protein kinase activity, thereby contributing to their anti-inflammatory effect by inhibiting IκB kinaseβactivation. Finally,in vivostudies demonstrated that both berberine (100 or 200 mg/kg) and nandinine (100 or 200 mg/kg) effectively ameliorated glucose intolerance and induced the insulin sensitivity index in mice. In conclusion, berberine and nandinine attenuated insulin resistance in adipocytes by inhibiting inflammation in an AMP-activated protein kinase-dependent manner. Berberine and nandinine may be used as dietary supplements and nandinine is a new candidate for obesity treatment.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Huzhou University, Huzhou, P. R. China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Ge
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, P. R. China.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Baolin
authors.initials: B
authors.lastname: Liu
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D001600:Berberine Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012459:Salicylates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase; D001600:Berberine Alkaloids; D005947:Glucose; D051550:I-kappa B Kinase; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D015850:Interleukin-6; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D012459:Salicylates; D014409:Tumor Necrosis Factor-alpha; D000097782:NF-kappaB-Inducing Kinase; C577686:interleukin-6, mouse