title: 1H NMR-based metabolomics study of liver damage induced by ginkgolic acid (15:1) in mice.
abstract: Ginkgolic acid (15:1) is a major toxic component in extracts obtained from Ginkgo biloba (EGb) that has allergic and genotoxic effects. This study is the first to explore the hepatotoxicity of ginkgolic acid (15:1) using a NMR (nuclear magnetic resonance)-based metabolomics approach in combination with biochemistry assays. Mice were orally administered two doses of ginkgolic acid (15:1), and mouse livers and serum were then collected for NMR recordings and biochemical assays. The levels of activity of alanine aminotransferase (ALT) and glutamic aspartate transaminase (AST) observed in the ginkgolic acid (15:1)-treated mice suggested that it had induced severe liver damage. An orthogonal signal correction partial least-squares discriminant analysis (OSC-PLSDA) performed to determine the metabolomic profile of mouse liver tissues indicated that many metabolic disturbances, especially oxidative stress and purine metabolism, were induced by ginkgolic acid (15:1). A correlation network analysis combined with information related to structural similarities further confirmed that purine metabolism was disturbed by ginkgolic acid (15:1). This mechanism might represent the link between the antitumour activity and the liver injury-inducing effect of ginkgolic acid (15:1). A SUS (Shared and Unique Structure) plot suggested that a two-dose treatment of ginkgolic acid (15:1) had generally the same effect on metabolic variations but that its effects were dose-dependent, revealing some of the common features of ginkgolic acid (15:1) dosing. This integrated metabolomics approach helped us to characterise ginkgolic acid (15:1)-induced liver damage in mice.
authors.affiliation: Centre for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing 210094, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Centre for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing 210094, PR China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Si
authors.affiliation: Centre for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing 210094, PR China.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Li
authors.affiliation: Centre for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing 210094, PR China.
authors.forename: He
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Centre for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing 210094, PR China.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Fu
authors.affiliation: Centre for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing 210094, PR China.
authors.forename: Yue-Xiao
authors.initials: YX
authors.lastname: Xing
authors.affiliation: Centre for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing 210094, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hong
authors.affiliation: Centre for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing 210094, PR China.
authors.forename: Ling-Yu
authors.initials: LY
authors.lastname: Ruan
authors.affiliation: Centre for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing 210094, PR China.
authors.forename: Pu-Min
authors.initials: PM
authors.lastname: Li
authors.affiliation: Centre for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei Street, Nanjing 210094, PR China. Electronic address: wang.junsong@gmail.com.
authors.forename: Jun-Song
authors.initials: JS
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D008813:Mice, Inbred ICR; D019906:Nuclear Magnetic Resonance, Biomolecular; D012459:Salicylates / Q000633:toxicity*
chemical_list: D012459:Salicylates; C112485:ginkgolic acid
keywords: Ginkgolic acid (15:1); Metabolomics; Mice; NMR