title: Antiobesity and Antidiabetes Effects of a Cudrania tricuspidata Hydrophilic Extract Presenting PTP1B Inhibitory Potential.
abstract: Diabetes and obesity represent the major health problems and the most age-related metabolic diseases. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as an important regulator of insulin signal transduction and is regarded as a pharmaceutical target for metabolic disorders. To find novel natural materials presenting therapeutic activities against diabetes and obesity, we screened various herb extracts using a chip screening allowing the determination of PTP1B inhibitory effects of the tested compounds using insulin receptor (IR) as the substrate. Cudrania tricuspidata leaves (CTe) had a strong inhibitory effect on PTP1B activity and substantially inhibited fat accumulation in 3T3-L1 cells. CTe was orally administrated to diet-induced obesity (DIO) mice once daily for 3 weeks after which changes in glucose, insulin metabolism, and fat accumulation were examined. Hepatic enzyme markers (aspartate aminotransferase, AST, and alanine aminotransferase, ALT) and total fat mass and triglyceride levels decreased in CTe-treated mice, whereas body weight and total cholesterol concentration slightly decreased. CTe increased the phosphorylation of IRS-1 and Akt in liver tissue. Furthermore, CTe treatment significantly lowered blood glucose levels and improved insulin secretion in DIO mice. Our results strongly suggest that CTe may represent a promising therapeutic substance against diabetes and obesity.
authors.affiliation: New Drug Discovery Laboratory, Hyundai Pharmaceutical Co. Ltd., Gyeong-Gi Bio-Center, Lui-dong, Yeongtong-gu, Suwon, Gyeonggi-do, Republic of Korea.
authors.forename: Dae Hoon
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Chuncheon Bioindustry Foundation, Natural Resources Commercialization Center, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Sooung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Yonsei Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Youn Wook
authors.initials: YW
authors.lastname: Chung
authors.affiliation: Severance Integrative Research Institute for Cerebral & Cardiovascular Diseases (SIRIC), Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Byeong Mo
authors.initials: BM
authors.lastname: Kim
authors.affiliation: Brain Korea 21 Project for Medical Science, Yonsei University, Seoul, Republic of Korea; Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hanseul
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kunhong
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung Mi
authors.initials: KM
authors.lastname: Yang
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008820:Mice, Obese; D029586:Moraceae / Q000737:chemistry; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007328:Insulin; D010936:Plant Extracts; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse