DanHong injection dose-dependently varies amino acid metabolites and metabolic pathways in the treatment of rats with cerebral ischemia.
OBJECTIVE
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.


CONCLUSIONS
Overlapping and non-overlapping amino acid metabolites and metabolic pathways are associated with the dose-dependent neuroprotective effect of DHI.
1] Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China [2] Jiaxing Traditional Chinese Medicine Affiliated Hospital of Zhejiang Chinese Medical University, Jiaxing 314000, China.
Zhi-li
ZL
Guo
1] Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China [2] Beijing Electric Power Hospital, Capital Medical University, Beijing 10073, China [3] Xi'an Buchang Pharmaceutical Co, Ltd, Xi'an 712000, China.
Yan
Y
Zhu
Xi'an Buchang Pharmaceutical Co, Ltd, Xi'an 712000, China.
Xiao-tao
XT
Su
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Jun
J
Liu
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
Qian-xu
QX
Yang
Xi'an Buchang Pharmaceutical Co, Ltd, Xi'an 712000, China.
Jing-yi
JY
Nan
Xi'an Buchang Pharmaceutical Co, Ltd, Xi'an 712000, China.
Bu-chang
BC
Zhao
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Ying-ying
YY
Zhang
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Ya-nan
YN
Yu
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Bing
B
Li
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
Hong-bin
HB
Xiao
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Zhong
Z
Wang
D000596:Amino Acids / Q000097:blood*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000097:blood / Q000175:diagnosis / Q000517:prevention & control*; D008297:Male; D008516:Medicine, Chinese Traditional / Q000379:methods*; D055432:Metabolomics / Q000379:methods*; D015999:Multivariate Analysis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D049490:Systems Biology / Q000379:methods*; D018511:Systems Integration
D000596:Amino Acids; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; C540581:danhong