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DanHong injection dose-dependently varies amino acid metabolites and metabolic pathways in the treatment of rats with cerebral ischemia
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DanHong injection dose-dependently varies amino acid metabolites and metabolic pathways in the treatment of rats with cerebral ischemia
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DanHong injection dose-dependently varies amino acid metabolites and metabolic pathways in the treatment of rats with cerebral ischemia
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Journal Article
DanHong injection dose-dependently varies amino acid metabolites and metabolic pathways in the treatment of rats with cerebral ischemia
2015
Overview
Aim： To determine how the relative amino acid contents and metabolic pathways regulate the pharmacological phenotypes in rats with cerebral ischemia after treatment with varying doses of DanHong injection （DHI）. Methods： Adult male rats underwent middle cerebral artery occlusion （MCAO）, and were injected with DHI （DH-1： 1 mL/kg; DH-2： 2.5 mL/kg; DH-3：5 mL/kg, and DH-4：10 mL/kg, iv） daily for 3 d. The neurological deficit score, body weights and infarct volume were assessed. Serum levels of 20 free amino acids were determined using HPLC, and the values were transformed through the quantitative analysis of the amino acids in the serum metabolic spectrum. Multivariate statistical analysis methods （PCA and PLS-DA） and web-based metabolomics tools （MetPa and MetaboAnalyst） were used to analyze the biological data sets for the amino acids. Results： Administration of DHI dose-dependently decreased cerebral infarct volume, and ameliorated neurological deficits. A total of 5, 6, 7 and 7 non-overlapping metabolites were identified in the DH-1, DH-2, DH-3, and DH-4 groups, respectively. Eight metabolites were shared between the DHI groups and the vehicle group. In addition, the serum levels of glutamic acid, aspartic acid and serine increased with increasing DHI dose. A total of 3, 2, 2 and 5 non-overlapping metabolic pathways were identified in the DH-1, DH-2, DH-3 and DH-4 groups, respectively, and glycine, serine, threonine and histidine metabolism were identified as overlapping pathways among the 4 dose groups. Conclusion： Overlapping and non-overlapping amino acid metabolites and metabolic pathways are associated with the dose-dependent neuroprotective effect of DHI.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Biomedical and Life Sciences
/ Chromatography, High Pressure Liquid
/ Dose-Response Relationship, Drug
/ Drugs, Chinese Herbal - pharmacology
/ Infarction, Middle Cerebral Artery - blood
/ Infarction, Middle Cerebral Artery - diagnosis
/ Infarction, Middle Cerebral Artery - prevention & control
/ Male
/ Medicine, Chinese Traditional - methods
/ Neuroprotective Agents - pharmacology
/ Original
/ Vaccine
/ 代谢产物
/ 代谢途径
/ 依赖性
/ 大剂量
/ 氨基酸含量
/ 注射液
/ 脑缺血
/ 雄性大鼠
