title: Hypoglycemic effect and mechanism of honokiol on type 2 diabetic mice.
abstract: BACKGROUND
  Honokiol is one of the main bioactive constituents of the traditional Chinese herbal drug Magnolia bark (Cortex Magnoliae officinalis, Hou Po). The aim of this study was to probe its anti-type 2 diabetes mellitus effects and the underlying mechanism.
  
  
  METHODS
  Type 2 diabetic mouse model was established by intraperitoneally injecting with streptozotocin. Fasting blood glucose, body weight, and lipid profile were measured. The subcutaneous adipose tissue, skeletal muscle, and liver were isolated as well as homogenized. The phospho-insulin receptor β-subunit (IRβ), IRβ, phospho-AKT, AKT, phospho-ERK1/2, ERK1/2, phosphotyrosine, and actin were examined by Western blot assay. Cell viability or cytotoxicity was analyzed by using MTT method. The inhibitory potencies of honokiol on the protein tyrosine phosphatase 1B (PTP1B) activity were performed in reaction buffer. Molecular docking and dynamic simulation were also analyzed.
  
  
  RESULTS
  In in vivo studies, oral treatment with 200 mg/kg honokiol for 8 weeks significantly decreases the fasting blood glucose in type 2 diabetes mellitus mice. The phosphorylations of the IRβ and the downstream insulin signaling factors including AKT and ERK1/2 significantly increase in adipose, skeletal muscle, and liver tissue of the honokiol-treated mice. Moreover, honokiol enhanced the insulin-stimulated phosphorylations of IRβ, AKT, and ERK1/2 in a dose-dependent manner in C2C12 myotube cells. Meanwhile, honokiol enhanced insulin-stimulated GLUT4 translocation. Importantly, honokiol exhibited reversible competitive inhibitory activity against PTP1B with good selectivity in vitro and in vivo. Furthermore, using molecular docking and dynamic simulation approaches, we determined the potential binding mode of honokiol to PTP1B at an atomic level.
  
  
  CONCLUSIONS
  These findings indicated the hypoglycemic effects of honokiol and its mechanism that honokiol improved the insulin sensitivity by targeting PTP1B. Therefore, our study may highlight honokiol as a promising insulin sensitizer for the therapy of type 2 diabetes.
authors.affiliation: School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: School of Life Sciences, Jilin University, Changchun, People's Republic of China ; Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun, People's Republic of China ; National Engineering Laboratory of AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Xueqi
authors.initials: X
authors.lastname: Fu
authors.affiliation: School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Yongsen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Huo
authors.affiliation: School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Yidi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Gao
authors.affiliation: School of Life Sciences, Jilin University, Changchun, People's Republic of China ; Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun, People's Republic of China ; National Engineering Laboratory of AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Wannan
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Life Sciences, Jilin University, Changchun, People's Republic of China ; Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun, People's Republic of China ; National Engineering Laboratory of AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D017705:Lignans / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013311:Streptozocin; D013329:Structure-Activity Relationship; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D017705:Lignans; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D013311:Streptozocin; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C516609:Ptpn1 protein, mouse
keywords: PTP1B; T2DM; honokiol; insulin sensitizer