Zhang Mengqi, Li Peihai, Zhang Shanshan, Zhang Xuanming, Wang Lizhen, Zhang Yun, Li Xiaobin, Liu Kechun
Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Key Laboratory for Biosensor of Shandong Province, Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250103, China.
State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250353, China.
ACS Omega. 2021 May 25;6(22):14677-14691. doi: 10.1021/acsomega.1c01847. eCollection 2021 Jun 8.
Danggui-Chuanxiong (DC) is a commonly used nourishing and activating blood medicine pair in many gynecological prescriptions and modern Chinese medicine. However, its activating blood mechanism has not been clearly elucidated. Our research aimed at investigating the activating blood mechanisms of DC using network pharmacology and zebrafish experiments. Network pharmacology was used to excavate the potential targets and mechanisms of DC in treating thrombus. The antithrombotic, anti-inflammatory, antioxidant, and vasculogenesis activities of DC and the main components of DC, ferulic acid (DC2), ligustilide (DC7), and levistilide A (DC17), were evaluated by zebrafish models in vivo. A total of 24 compounds were selected as the active ingredients with favorable pharmacological parameters for this herb pair. A total of 89 targets and 18 pathways related to the thrombus process were gathered for active compounds. The genes, TNF, CXCR4, IL2, ESR1, FGF2, HIF1A, CXCL8, AR, FOS, MMP2, MMP9, STAT3, and RHOA, might be the main targets for this herb pair to exert cardiovascular activity from the analysis of protein-protein interaction and KEGG pathway results, which were mainly related to inflammation, vasculogenesis, immunity, hormones, and so forth. The zebrafish experiment results showed that DC had antithrombotic, anti-inflammatory, antioxidant, and vasculogenesis activities. The main compounds had different effects of zebrafish activities. Especially, the antithrombotic activity of the DC17H group, anti-inflammatory activities of DCH and DC2H groups, antioxidant activities of DCM, DCH, DC2, DC7, and DC17 groups, and vasculogenesis activities of DCM, DCH, and DC2 groups were stronger than those of the positive group. The integrated method coupled zebrafish models with network pharmacology provided the insights into the mechanisms of DC in treating thrombus.
当归 - 川芎（DC）是许多妇科方剂和现代中药中常用的养血活血药对。然而，其活血机制尚未完全阐明。我们的研究旨在通过网络药理学和斑马鱼实验来探究DC的活血机制。利用网络药理学挖掘DC治疗血栓的潜在靶点和机制。通过斑马鱼体内模型评估DC及其主要成分阿魏酸（DC2）、藁本内酯（DC7）和洋川芎内酯A（DC17）的抗血栓、抗炎、抗氧化和血管生成活性。共筛选出24种化合物作为该药对具有良好药理参数的活性成分。共收集到89个与血栓形成过程相关的靶点和18条通路用于活性化合物研究。通过蛋白质 - 蛋白质相互作用和KEGG通路结果分析，基因TNF、CXCR4、IL2、ESR1、FGF2、HIF1A、CXCL8、AR、FOS、MMP2、MMP9、STAT3和RHOA可能是该药对发挥心血管活性的主要靶点，这些靶点主要与炎症、血管生成、免疫、激素等相关。斑马鱼实验结果表明DC具有抗血栓、抗炎、抗氧化和血管生成活性。主要化合物对斑马鱼活性有不同影响。特别是，DC17H组的抗血栓活性、DCH和DC2H组的抗炎活性、DCM、DCH、DC2、DC7和DC17组 的抗氧化活性以及DCM、DCH和DC2组的血管生成活性均强于阳性组。将斑马鱼模型与网络药理学相结合的综合方法为DC治疗血栓的机制提供了深入见解。
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