Li Shujiao, Lin Hang, Tang Yuping, Li Weixia, Shen Juan, Kai Jun, Yue Shijun, Shang Guanxiong, Zhu Zhenhua, Shang Erxin, Zhang Changbin, Zhang Li, Yan Hui, Liu Pei, Duan Jin-ao
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
J Pharm Biomed Anal. 2015 Mar 25;107:456-63. doi: 10.1016/j.jpba.2015.01.029. Epub 2015 Jan 23.
The compatibility of Angelicae Sinensis Radix (Danggui, DG) and Flos Carthami (Honghua, HH), a famous herb pair Gui-Hong (GH), can produce synergistic and promoting blood effects. Although some physiological and pathological function parameters of the acute blood stasis have been investigated, little information about the changes of small metabolites in biofluids has been reported. In present study, global metabolic profiling with ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) combined with pattern recognition method was performed to discover the underlying blood-activating regulation mechanisms of DG, HH and GH on the acute blood stasis rats induced by subcutaneous injection of adrenaline hydrochloride and ice water bath. The total 14 metabolites (10 in urine and 4 in plasma), up regulated or down regulated (P<0.05 or 0.01), were identified and contributed to the acute blood stasis progress. These promising identified biomarkers underpin the metabolic pathway including phenylalanine metabolism, sphingolipid metabolism, arachidonic acid metabolism and arginine and proline metabolism are disturbed in the acute blood stasis rats, which identified by using pathway analysis with MetPA. The altered metabolites and hemorheological indexes could be regulated closer to normal level after DG, HH and GH intervention. In term of activate blood circulation function, GH was the most effective as shown by the relative distance in PLS-DA score plots and relative intensity of metabolomics trategy, reflecting the synergic action between Danggui and Honghua. The results demonstrated that biofluids metabolomics was a powerful tool in clinical diagnosis and treatment of syndrome of blood stasis for providing information on changes in metabolites pathways.
当归（Danggui，DG）与红花（Flos Carthami，HH）这一著名药对“归红”（Gui-Hong，GH）配伍具有协同增效、活血化瘀的作用。尽管已有研究探讨了急性血瘀证的部分生理病理功能参数，但关于生物流体中小分子代谢物变化的报道较少。本研究采用超高效液相色谱-四极杆飞行时间质谱联用技术（UHPLC-QTOF/MS）结合模式识别方法，对皮下注射肾上腺素加冰水浴诱导的急性血瘀大鼠进行整体代谢轮廓分析，以揭示DG、HH及GH对急性血瘀的潜在活血化瘀调节机制。共鉴定出14种代谢物（尿液中10种，血浆中4种），其表达上调或下调（P<0.05或0.01），这些代谢物参与了急性血瘀的进程。通过MetPA通路分析确定，这些有前景的生物标志物所涉及的代谢途径包括苯丙氨酸代谢、鞘脂代谢、花生四烯酸代谢以及精氨酸和脯氨酸代谢在急性血瘀大鼠中受到干扰。DG、HH及GH干预后，代谢物变化和血液流变学指标可调节至接近正常水平。在活血化瘀方面，从PLS-DA得分图中的相对距离和代谢组学策略的相对强度来看，GH最为有效，体现了当归与红花的协同作用。结果表明，生物流体代谢组学可为血瘀证的临床诊断和治疗提供代谢物途径变化信息，是一种有力工具。
