title: Leaf Extract from Lithocarpus polystachyus Rehd. Promote Glycogen Synthesis in T2DM Mice.
abstract: The purpose of this study was to investigate the effects of leaf extract from Lithocarpus polystachyus Rehd. on type II diabetes mellitus (T2DM) and the active ingredients of this effect. In addition, this study determined, for the first time, the underlying molecular and pharmacological mechanisms of the extracts on hyperglycemia using long-term double high diet-fed and streptozotocin (STZ) induced type II diabetic mice. In the present study, leaf extract, phloridzin and trilobatin were assessed in vivo (gavage) and in vitro (non-invasive micro-test technique, NMT) in experimental T2DM mice. The biochemical parameters were measured including blood glucose and blood lipid level, liver biochemical indexes, and hepatic glycogen. The relative expression of glycometabolism-related genes was detected. The effect of leaf extracts on physiological glucose flux in liver tissue from control and T2DM mice was also investigated. Body weight of experimental T2DM mice increased significantly after the first week, but stabilized over the subsequent three weeks; body weight of all other groups did not change during the four weeks' study. After four weeks, all treatment groups decreased blood glucose, and treatment with leaf extract had numerous positive effects: a) promoted in glucose uptake in liver, b) increased synthesis of liver glycogen, c) reduced oxidative stress, d) up-regulation of glucokinase (GK), glucose transporter 2 (GLUT2), insulin receptor (IR) and insulin receptor substrate (IRS) expression in liver, e) down-regulation of glucose-6-phosphatase (G-6-P) expression, and f) ameliorated blood lipid levels. Both treatment with trilobatin or phloridzin accelerated liver glycogen synthesis, decreased oxidative stress and increased expression of GK. IRS and phosphoenolpyruvate carboxykinase (PEPCK) were both up-regulated after treatment with trilobatin. Expression of GLUT2, PEPCK and G-6-P were also increased in liver tissue after treatment with phloridzin. Our data indicate that leaf extract from L. polystachyus Rehd. has a preferable hypoglycemic effects than trilobatin or phloridzin alone. Leaf extract significantly increased glucose uptake and hepatic glycogen synthesis while also inducing a decline of hepatic gluconeogenesis and oxidative stress in T2DM mice. From this study, we draw conclusions that L. polystachyus promoted glycogen synthesis in T2DM mice, and that the active compounds were not only the trilobatin or phloridzin.
authors.affiliation: College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China.
authors.forename: Jinfei
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Huang
authors.affiliation: College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China.|Guangxi Forestry Research Institute, Nanning, Guangxi, China.
authors.forename: Kaixiang
authors.initials: K
authors.lastname: Li
authors.affiliation: College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Food Engineering Department, Universidad del Valle, Cali, Valle del Cauca, Colombia.
authors.forename: Diana
authors.initials: D
authors.lastname: Vanegas
authors.affiliation: Agricultural and Biological Engineering Department, Institute of Agricultural and Food Science, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Eric Scott
authors.initials: ES
authors.lastname: McLamore
authors.affiliation: College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China.
authors.forename: Yingbai
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000591:Amino Acid Isomerases / Q000032:analysis; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D015536:Down-Regulation / Q000187:drug effects; D029962:Fagaceae / Q000737:chemistry* / Q000378:metabolism; D005951:Glucose Tolerance Test; D005978:Glutathione / Q000032:analysis; D006003:Glycogen / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry / Q000378:metabolism; D013311:Streptozocin / Q000633:toxicity; D013482:Superoxide Dismutase / Q000032:analysis; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D008315:Malondialdehyde; D013311:Streptozocin; D006003:Glycogen; D013482:Superoxide Dismutase; D000591:Amino Acid Isomerases; C062292:glutamate racemase; D005978:Glutathione