title: Magnolia officinalis Extract Contains Potent Inhibitors against PTP1B and Attenuates Hyperglycemia in db/db Mice.
abstract: Protein tyrosine phosphatase 1B (PTP1B) is an established therapeutic target for type 2 diabetes mellitus (T2DM) and obesity. The aim of this study was to investigate the inhibitory activity of Magnolia officinalis extract (ME) on PTP1B and its anti-T2DM effects. Inhibition assays and inhibition kinetics of ME were performed in vitro. 3T3-L1 adipocytes and C2C12 myotubes were stimulated with ME to explore its bioavailability in cell level. The in vivo studies were performed on db/db mice to probe its anti-T2DM effects. In the present study, ME inhibited PTP1B in a reversible competitive manner and displayed good selectivity against PTPs in vitro. Furthermore, ME enhanced tyrosine phosphorylation levels of cellular proteins, especially the insulin-induced tyrosine phosphorylations of insulin receptor β-subunit (IRβ) and ERK1/2 in a dose-dependent manner in stimulated 3T3-L1 adipocytes and C2C12 myotubes. Meanwhile, ME enhanced insulin-stimulated GLUT4 translocation. More importantly, there was a significant decrease in fasting plasma glucose level of db/db diabetic mice treated orally with 0.5 g/kg ME for 4 weeks. These findings indicated that improvement of insulin sensitivity and hypoglycemic effects of ME may be attributed to the inhibition of PTP1B. Thereby, we pioneered the inhibitory potential of ME targeted on PTP1B as anti-T2DM drug discovery.
authors.affiliation: Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Yongsen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Xueqi
authors.initials: X
authors.lastname: Fu
authors.affiliation: Academy of Traditional Chinese Medicine and Chinese Medicinal Materials of Jilin Province, Changchun 130012, China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Deli
authors.initials: D
authors.lastname: Wang
authors.affiliation: Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun 130012, China ; Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
authors.forename: Wannan
authors.initials: W
authors.lastname: Li
authors.affiliation: Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Xing
authors.affiliation: Department of Colorectal and Anal Surgery, The Second Hospital, Jilin University, Changchun 130041, China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Li
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D051275:Glucose Transporter Type 4 / Q000235:genetics; D006943:Hyperglycemia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D031566:Magnolia / Q000737:chemistry; D051379:Mice; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010936:Plant Extracts / Q000008:administration & dosage*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D010936:Plant Extracts; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse