title: Evaluation of dose-related effects of 2', 3', 5'-tri-O-acetyl-N6-(3-hydroxylaniline)adenosine using NMR-based metabolomics.
abstract: 2', 3', 5'-Tri-O-acetyl-N6-(3-hydroxylaniline)adenosine (WS070117) is a derivative compound of natural product cordycepin. It has significant lipids regulating activity and low toxicity which has been proved by in vitro and in vivo experiments. In this study, 1H NMR-based metabolomics was used to investigate the dose-related effects of WS070117 on hyperlipidemia of high-fat-fed hamsters. The hyperlipidemic hamsters were administrated with six different doses of WS070117, including 3, 12, 50, 100, 200 and 400 mg x kg(-1) x d(-1). 1H NMR spectra of hamster serum were visually and statistically analyzed using two multivariate analyses: principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). As a result, WS070117-treated groups showed dose-related regulation of metabolites associated with lipid metabolism, choline metabolism and glucose metabolism. The dose of 3 mg x kg(-1) x d(-1) of WS070117 only exhibited a little lipids regulating activity. However, the doses of 12 and 50 mg x kg(-1) x d(-1) of WS070117 both regulated the contents of metabolites to reverse significantly toward normal levels. When the dose of WS070117 reached 100 mg x kg(-1) x d(-1), it was more effective than positive control drugs. The work suggested that NMR-based metabolomics might be a valuable approach to evaluate dose-related effects of lipids regulating compounds.
authors.forename: Zhao-Xia
authors.initials: ZX
authors.lastname: Miao
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Chun-Ying
authors.initials: CY
authors.lastname: Jiang
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Wang
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Zhu
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D006224:Cricetinae; D006949:Hyperlipidemias / Q000378:metabolism; D016018:Least-Squares Analysis; D050356:Lipid Metabolism / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics; D015999:Multivariate Analysis; D025341:Principal Component Analysis
chemical_list: C561084:O2',O3',O5'-triacetyl-N6-(3-hydroxylaniline)adenosine; D000241:Adenosine