School of Bioscience and Biopharmaceutics, Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, 510006, Guangzhou, Guangdong, China.
College of Pharmacy, Guangdong Pharmaceutical University, 510006, Guangzhou, Guangdong, China.
Complement Ther Med. 2020 Jan;48:102247. doi: 10.1016/j.ctim.2019.102247. Epub 2019 Nov 21.
Danggui Buxue Tang has been used for menopausal women in China for more than 800 years. However, the potential effective ingredients and pathways require further investigation. The main objective of this work was to explore the potential effective ingredients and pathways. The optimal administration time was optimized by detecting the changes of reticulocytes in peripheral blood. Drug-containing serum (DCS) was taken every 30 min after last administration. Because of the different concentration of effective ingredients absorbed into blood at different time, the pharmacodynamic effect is different. Therefore, bone marrow stromal cells as a member of hematopoietic microenvironment were used to evaluate the pharmacodynamics of DCS. Metabolomics was used to detect changes of metabolites (DBT and endogenous metabolites). The correlation of the metabolites and pharmacodynamics was used to identify the metabolites associated with erythropoiesis. After 14 days, the number of reticulocytes in peripheral blood, erythroid-related cells and erythroid progenitor cells in bone marrow in the DBT group were significantly increased. In vitro experiments showed that DCS at different time had different proliferation effects on BMSCs. Metabolomic analysis showed that the concentration of metabolites in DCS at different time was significantly different. The correlation analysis identified 7 DBT metabolites and 15 endogenous metabolites related to erythropoiesis. 15 endogenous metabolites were finally connected to different pathways. Glutamate is a node molecule. 7 potential effective ingredients of DBT were found. DBT promoted erythropoiesis via promoting the metabolism of glutamate and further affect other pathways.
当归补血汤在中国已被用于治疗更年期妇女超过 800 年。然而，其潜在的有效成分和作用途径仍需进一步研究。本研究旨在探索当归补血汤的潜在有效成分和作用途径。通过检测外周血网织红细胞的变化来优化最佳给药时间。末次给药后每 30 分钟采集含药血清（DCS）。由于不同时间有效成分在血液中的吸收浓度不同，药效也不同。因此，骨髓基质细胞作为造血微环境的一部分，用于评估 DCS 的药效。代谢组学用于检测代谢物（DBT 和内源性代谢物）的变化。将代谢物与药效的相关性用于鉴定与红细胞生成相关的代谢物。14 天后，DBT 组外周血网织红细胞数、骨髓中红系相关细胞和红系祖细胞均明显增加。体外实验表明，不同时间的 DCS 对 BMSCs 有不同的增殖作用。代谢组学分析显示，不同时间 DCS 中的代谢物浓度差异显著。相关性分析鉴定出与红细胞生成相关的 7 种 DBT 代谢物和 15 种内源性代谢物。最终，这 15 种内源性代谢物与不同的途径相连。谷氨酸是一个节点分子。发现了 7 种 DBT 的潜在有效成分。DBT 通过促进谷氨酸代谢来促进红细胞生成，从而进一步影响其他途径。
