title: Combining biochemical with (1)H NMR-based metabolomics approach unravels the antidiabetic activity of genipin and its possible mechanism.
abstract: Diabetes mellitus is a typical heterogeneous metabolic disorder characterized by abnormal metabolism of carbohydrates, lipids and proteins. Genipin possesses a wide spectrum of biological activities including ameliorating effects on diabetes, but the definite mechanism of this effect remains unknown. To investigate the antidiabetic activities of genipin and explore the biochemical changes of serum endogenous metabolites on diabetic rats induced by alloxan, (1)H NMR spectroscopy coupled with multivariate data analysis was used to. All rats were randomly divided into six groups including negative control (NC) group, diabetic mellitus (DM) group, metformin hydrochloride group, high dose group of genipin, middle dose group of genipin and low dose group of genipin. Diabetes was induced by a single intraperitoneal injection of 120mg/kg body weight of alloxan. Serum samples were collected for the (1)H NMR-based metabolomics and clinical biochemical analysis. Daily oral administration of genipin (25, 50 and 100mg/kg body weight) and metformin hydrochloride (125mg/kg) for two weeks showed beneficial effects on blood glucose level (P<0.01). Significant differences in the metabolic profile as well as the result of biochemical parameters between the diabetic group and the control group were observed. The PLS-DA scores and corresponding loading plots demonstrated that genipin significantly restored the abnormal metabolic state. Detailed analysis of the altered metabolite levels indicated that genipin significantly ameliorated the disturbance in glucose metabolism, tricarboxylic acid cycle, lipid metabolism and amino acid metabolism. Genipin showed the best anti-diabetic effects at a dose of 100mg/kg in rats. This finding indicates that chemical and metabolomic approaches could be powerful tools for the investigation of the biochemical changes in pathological conditions or drug treatment.
authors.affiliation: Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, PR China; College of Chemistry and Chemical Engineering of Shanxi University, Taiyuan 030006, PR China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Shen
authors.affiliation: Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, PR China; College of Chemistry and Chemical Engineering of Shanxi University, Taiyuan 030006, PR China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Physical Education Departments of Shanxi University, Taiyuan, 030006, PR China.
authors.forename: Huan
authors.initials: H
authors.lastname: Xiang
authors.affiliation: Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, PR China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Qin
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Du
authors.affiliation: Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, PR China. Electronic address: jstian@sxu.edu.cn.
authors.forename: Jun-Sheng
authors.initials: JS
authors.lastname: Tian
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D039823:Iridoids / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D055442:Metabolome / Q000502:physiology; D055432:Metabolomics / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D039823:Iridoids; C007834:genipin
keywords: Antidiabetic activity; Biochemical changes; Genipin; Metabolomics; Nuclear magnetic resonance