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Molecules 2017, 22(9), 1443;

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

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
College of Preclinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China
Shandong Buchang Pharmaceutical Co., Ltd., Heze 274000, China
Authors to whom correspondence should be addressed.
Received: 1 August 2017 / Revised: 24 August 2017 / Accepted: 25 August 2017 / Published: 31 August 2017
(This article belongs to the Collection Herbal Medicine Research)
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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. View Full-Text
Keywords: Chinese medicine; batch-to-batch consistency; zebrafish thrombosis model; rosmarinic acid; p-coumaric acid Chinese medicine; batch-to-batch consistency; zebrafish thrombosis model; rosmarinic acid; p-coumaric acid

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Qi, Y.; Zhao, X.; Liu, H.; Wang, Y.; Zhao, C.; Zhao, T.; Zhao, B.; Wang, Y. Identification of a Quality Marker (Q-Marker) of Danhong Injection by the Zebrafish Thrombosis Model. Molecules 2017, 22, 1443.

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