Wang Lu, Huang Shuai, Chen Bing, Zang Xin-Yu, Su Dan, Liang Jing, Xu Feng, Liu Guang-Xue, Shang Ming-Ying, Cai Shao-Qing
Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Guangxi Institute of Botany, Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guilin, China.
Planta Med. 2016 Mar;82(4):362-70. doi: 10.1055/s-0035-1558309. Epub 2016 Feb 1.
Angelicae Sinensis Radix is commonly used in traditional Chinese medicine. Pharmacological studies show that Angelicae Sinensis Radix has clear anticoagulant activity. Therefore, in this study, the anticoagulant activity of crude Angelicae Sinensis Radix extracts was investigated by measuring the thrombin times of the extracts. The results revealed that the petroleum ether-soluble fraction of Angelicae Sinensis Radix exhibited significant anticoagulant activity in vitro, and 26 compounds were characterized by high-performance liquid chromatography with diode array detection combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry. In addition, 5 prototype constituents, 24 in vivo metabolites in rat urine and 7 prototype constituents, and 9 in vitro metabolites in the rat hepatic S9 incubation system of the petroleum ether-soluble fraction were tentatively identified. All metabolites were found from Angelicae Sinensis Radix for the first time. Among them, 13 (three ferulic acid-related constituents, six senkyunolide D-related constituents, and four senkyunolide F-related constituents) were identified as new metabolites (new compounds). This study is the first to qualitatively characterize the chemical constituents of the potent anticoagulative extract of Angelicae Sinensis Radix and to explore its metabolism. The result is a notable improvement in the discovery of Angelicae Sinensis Radix metabolites, and it provides the chemical basis for the effective forms and pharmacodynamic substances (prototypes, metabolites, or both) of the anticoagulant activity of Angelicae Sinensis Radix.
当归常用于传统中药。药理学研究表明，当归具有明确的抗凝活性。因此，在本研究中，通过测量当归粗提取物的凝血酶时间来研究其抗凝活性。结果显示，当归的石油醚可溶部分在体外表现出显著的抗凝活性，并且通过二极管阵列检测的高效液相色谱结合电喷雾电离离子阱飞行时间多级质谱对26种化合物进行了表征。此外，初步鉴定了石油醚可溶部分的5种原型成分、大鼠尿液中的24种体内代谢产物以及7种原型成分，以及大鼠肝脏S9孵育系统中的9种体外代谢产物。所有代谢产物均首次从当归中发现。其中，13种（三种阿魏酸相关成分、六种蛇床子素D相关成分和四种蛇床子素F相关成分）被鉴定为新的代谢产物（新化合物）。本研究首次对抗凝活性强的当归提取物的化学成分进行了定性表征，并探索了其代谢情况。该结果在当归代谢产物的发现方面有显著改进，并为当归抗凝活性的有效形式和药效物质（原型、代谢产物或两者）提供了化学依据。
