PUBLICATION

Identification of a Quality Marker (Q-Marker) of Danhong Injection by the Zebrafish Thrombosis Model

Authors
Qi, Y., Zhao, X., Liu, H., Wang, Y., Zhao, C., Zhao, T., Zhao, B., Wang, Y.
ID
ZDB-PUB-170901-2
Date
2017
Source
Molecules   22(9): (Journal)
Registered Authors
Keywords
Chinese medicine, batch-to-batch consistency, p-coumaric acid, rosmarinic acid, zebrafish thrombosis model
MeSH Terms
  • Animals
  • Arachidonic Acid
  • Biomarkers/blood
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Drugs, Chinese Herbal/administration & dosage*
  • Erythrocytes/drug effects
  • Fibrinolytic Agents/administration & dosage*
  • Injections
  • Myocardium/pathology
  • Thrombosis/chemically induced
  • Thrombosis/drug therapy*
  • Zebrafish
PubMed
28858254 Full text @ Molecules
Abstract
Quality-marker (Q-marker) is an emerging concept to ensure the quality and batch-to-batch consistency of Chinese medicine (CM). However, significant difficulties remain in the identification of Q-markers due to the unclear relationship between complex chemical compositions and the pharmacological efficacy of CM. In the present study, we proposed a novel strategy to identify the potential Q-marker of danhong injection (DHI) by an in vivo zebrafish thrombosis model. The anti-thrombotic effects of DHI and its major constituents were evaluated by the zebrafish model of arachidonic acid (AA)-induced thrombosis. The results indicated that DHI can attenuate tail venous thrombus and recover the decrease of heart red blood cell (RBC) intensity in a dose-dependent manner. The result that DHI prevented the formulation of thrombosis in zebrafish was also validated in the zebrafish thrombosis model with green fluorescence protein (GFP)-labeled hemoglobin. The major components of DHI, namely danshen (DS) and honghua (HH), as well as the major chemical constituents of DHI, also exerted anti-thrombotic effects, among which rosmarinic acid (RA) and p-coumaric acid (pCA) showed moderate anti-thrombotic effects. This is the first time that pCA from HH has been found as an active compound exerting an anti-thrombotic effect in a dose-dependent manner, whose IC50 value is approximately 147 μg/mL. By analyzing 10 batches of normal DHI samples and five abnormal samples by high-performance liquid chromatography (HPLC), we found the contents of pCA and RA can be positively correlated to the anti-thrombotic effect of DHI, suggesting that pCA and RA could be potential Q-markers of DHI to ensure batch-to-batch consistency. Our findings illustrated that discovering major active compounds from CM by in vivo pharmacological models can be a useful approach to identifying Q-markers of CM, and in vivo pharmacological models can be a potential tool to evaluate batch-to-batch consistency of CMs.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping