Cellular Metabolomics Revealed the Cytoprotection of Amentoflavone, a Natural Compound, in Lipopolysaccharide-Induced Injury of Human Umbilical Vein Endothelial Cells

Abstract

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.

Differential Metabolites and Metabolic Pathways Involved in Aerobic Exercise Improvement of Chronic Fatigue Symptoms in Adolescents Based on Gas Chromatography–Mass Spectrometry

“…The significant downregulation of citrulline levels and upregulation of proline and glutamate levels in students with CFS under the effect of aerobic exercise intervention indicated that the hydrolysis of arginine to urea and ornithine was restored. Spermine in the spermidine and proline metabolic pathway is produced from putrescine and S-adenosylmethionine catalyzed by various enzymes, providing greater stability and flexibility to DNA molecules, with a cell proliferation-promoting cell function [ 85 ]. Therefore, the ameliorative effect of aerobic exercise on fatigue in students with CFS may be related to the enhanced ability of the body to scavenge free radicals.…”

Acupuncture Synergized With Bortezomib Improves Survival of Multiple Myeloma Mice via Decreasing Metabolic Ornithine

“…Among them, ornithine as a unique downregulated metabolite in group VA was involved in the arginine and proline metabolic pathway, which showed the highest influence value ( Figures 5C, D ). Moreover, ornithine also participated in the regulation of glutathione metabolic pathway ( 43 , 44 ), which may play a role during VA treatment. Therefore, it was suggested that ornithine might be a promising biomarker of VA therapy for MM ( Figures 6A–C ).…”

LC-MS based cell metabolic profiling of tumor cells: a new predictive method for research on the mechanism of action of anticancer candidates

“…These intrinsic metabolism disorders may highly relate to their principal metabolic pathways, and maintain unlimited proliferation and thus are vulnerable to anticancer drugs that impair their vital metabolic pathways. 21 …”