Cellular Metabolomics Revealed the Cytoprotection of Amentoflavone, a Natural Compound, in Lipopolysaccharide-Induced Injury of Human Umbilical Vein Endothelial Cells.
Amentoflavone is one of the important bioactive flavonoids in the ethylacetate extract of "Cebaiye", which is a blood cooling and hematostatic herb in traditional Chinese medicine. The previous work in our group has demonstrated that the ethylacetate extract of Cebaiye has a notable antagonistic effect on the injury induced by lipopolysaccharide (LPS) to human umbilical vein endothelial cells (HUVECs). The present investigation was designed to assess the effects and possible mechanism of cytoprotection of amentoflavone via metabolomics. Ultra-performance liquid chromatography/quadrupole time of flight-mass spectrometry (UPLC/QTOF-MS) coupled with multivariate data analysis was used to characterize the variations in the metabolites of HUVECs in response to exposure to LPS and amentoflavone treatment. Seven putative metabolites (glycine, argininosuccinic acid, putrescine, ornithine, spermidine, 5-oxoproline and dihydrouracil) were discovered in cells incubated with LPS and/or amentoflavone. Functional pathway analysis uncovered that the changes of these metabolites related to various significant metabolic pathways (glutathione metabolism, arginine and proline metabolism, β-alanine metabolism and glycine, serine and threonine metabolism), which may explain the potential cytoprotection function of amentoflavone. These findings also demonstrate that cellular metabolomics through UPLC/QTOF-MS is a powerful tool for detecting variations in a range of intracellular compounds upon toxin and/or drug exposure.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. yaowf@njucm.edu.cn.|School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. yaowf@njucm.edu.cn.
Weifeng
W
Yao
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. missyhui2012@163.com.|School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. missyhui2012@163.com.
Hui
H
Li
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. liuqinan0728@163.com.|School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. liuqinan0728@163.com.
Qinan
Q
Liu
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. yegaohlgya@163.com.
Ye
Y
Gao
Department of Pathology, University of Washington, Seattle, WA 98195, USA. daij@u.washington.edu.
Jin
J
Dai
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. scotter01@163.com.|School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. scotter01@163.com.
Beihua
B
Bao
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. zhangli@njucm.edu.cn.|School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. zhangli@njucm.edu.cn.
Li
L
Zhang
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. awding105@163.com.|School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. awding105@163.com.
Anwei
A
Ding
D044946:Biflavonoids / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D019610:Cytoprotection; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects*; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods*; D015999:Multivariate Analysis
D044946:Biflavonoids; D008070:Lipopolysaccharides; C011164:amentoflavone
amentoflavone; cellular metabolomics; cytoprotection; human umbilical vein endothelial cells; lipopolysaccharide