Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization and Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae and Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization and Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae and Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China; Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xi'an 712046, Shaanxi Province, China.
J Ethnopharmacol. 2019 May 10;235:227-242. doi: 10.1016/j.jep.2019.01.027. Epub 2019 Jan 29.
Danggui buxue Decoction (DBD) has been frequently used to treat with blood deficiency, which consisted of Danggui (DG) and Huangqi (HQ) at a ratio of 1:5. Accumulating evidence showed that blood deficiency in traditional Chinese medicine (TCM) was similar to anemia in modern medicine.
The purpose of this study was to explore its therapeutic mechanism of with network pharmacology approach.
We explored the chemical compounds of DBD and used compound ADME screening to identify the potential compounds. Targets for the therapeutic actions of DBD were obtained from the PharmMapper, Swiss, SEA and STITCH. GO analysis and pathway enrichment analysis was performed using the DAVID webserver. Cytoscape was used to visualize the compound-target-pathway network for DBD. The pharmacodynamics and crucial targets were also validated.
Thirty-six potential active components in DBD and 49 targets which the active components acted on were identified. 47 KEGG pathways which DBD acted on were also come to light. And then, according to KEGG pathway annotation analysis, only 16 pathways seemed to be related to the blood nourishing effect of DBD, such as PI3K-AKT pathway, and so on. Only 32 targets participated in these 16 pathways and they were acted on by 29 of the 36 active compounds. Whole pharmacodynamic experiments showed that DBD had significant effects to blood loss rats. Furthermore, DBD could promote the up-regulation of hematopoietic and immune related targets and the down-regulation of inflammatory related targets. Significantly, with the results of effective rate, molecular docking and experimental validation, we predicted astragaloside IV in HQ, senkyunolide A and senkyunolide K in DG might be the major contributing compounds to DBD's blood enriching effect.
In this study, a systematical network pharmacology approach was built. Our results provided a basis for the future study of senkyunolide A and senkyunolide K as the blood enriching compounds in DBD. Furthermore, combined network pharmacology with validation experimental results, the nourishing blood effect of DBD might be manifested by the dual mechanism of enhancing immunity and promoting hematopoiesis.
当归补血汤（DBD）常用于治疗血虚症，由当归（DG）和黄芪（HQ）按 1:5 的比例组成。越来越多的证据表明，中医的血虚与现代医学的贫血相似。
本研究旨在采用网络药理学方法探讨其治疗机制。
我们探索了 DBD 的化学化合物，并使用化合物 ADME 筛选来识别潜在的化合物。DBD 治疗作用的靶点来自 PharmMapper、Swiss、SEA 和 STITCH。使用 DAVID 网络服务器进行 GO 分析和通路富集分析。使用 Cytoscape 可视化 DBD 的化合物-靶-通路网络。还验证了药效学和关键靶点。
鉴定出 DBD 中的 36 种潜在活性成分和活性成分作用的 49 个靶点。还揭示了 DBD 作用的 47 个 KEGG 通路。然后，根据 KEGG 通路注释分析，只有 16 条通路似乎与 DBD 的养血作用有关，如 PI3K-AKT 通路等。只有 32 个靶点参与了这 16 条通路，它们被 36 种活性成分中的 29 种作用。全药效实验表明，DBD 对失血性大鼠有显著作用。此外，DBD 可以促进造血和免疫相关靶点的上调和炎症相关靶点的下调。值得注意的是，通过有效率、分子对接和实验验证的结果，我们预测 HQ 中的黄芪甲苷 IV、DG 中的升麻素 A 和升麻素 K 可能是 DBD 养血作用的主要贡献化合物。
本研究建立了一种系统的网络药理学方法。我们的结果为今后研究升麻素 A 和升麻素 K 作为 DBD 的养血化合物提供了依据。此外，将网络药理学与验证实验结果相结合，DBD 的养血作用可能表现为增强免疫力和促进造血的双重机制。
