School of Bioscience and Biopharmaceutics, Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangdong 510006, China.
2 Department of Pharmacy, Zhanjiang Health School of Guangdong, Guangdong 524037, China.
J Tradit Chin Med. 2023 Jun;43(3):542-551. doi: 10.19852/j.cnki.jtcm.2023.03.004.
To investigate the underlying mechanism of Fanmugua (Fructus Caricae) Leaf (CPL) multicomponent synergistic therapy for anemia.
The components were identified in the literature. Six databases were searched for targets of CPL. Enrichment analysis was used to determine the targets associated with anemia and in bone marrow. Based on the Kyoto Encyclopedia of Genes and Genomes database, pathways and targets related to hematopoiesis were obtained. The key targets were obtained by protein-protein interaction analysis. Molecular docking was used to analyze the binding ability of key targets and active components. Bone marrow cells were used as an experimental model to verify the drug efficacy.
A total of 139 components and 1868 targets of CPL were retrieved from the literature. By disease enrichment analysis, 543 targets for hemorrhagic anemia, 223 targets for aplastic anemia, and 126 targets for sickle cell anemia were obtained. Target organ enrichment yielded 27, 29, and 20 targets of bone marrow. Based on KEGG pathway enrichment, a total of 47 shared hematopoietic pathways and 42 related targets were found. The key targets were vascular endothelial growth factor A (VEGFA), interleukin 10 (IL-10), platelet-endothelial cell adhesion molecule-1 (PECAM1), C-C motif chemokine 2 (CCL2), and vascular cell adhesion molecule 1 (VCAM1). The CPL active components included ursolic acid, quercetin, and hesperidin. The expression of VEGFA was significantly increased after CPL treatment. Quercetin and ursolic acid acted on VEGFA. Quercetin and Hesperidin acted on VCAM1. Quercetin acted on IL-10, CCL2, VCAM1, and VEGFA. Cell experiments revealed that CPL could promote the proliferation and migration of bone marrow cells.
CPL has the synergistic efficacy of treating anemia through multiple components, targets, and pathways.
研究番木瓜叶（CPL）多成分协同治疗贫血的潜在机制。
从文献中鉴定成分。在六个数据库中搜索 CPL 的靶点。利用富集分析确定与贫血和骨髓相关的靶点。基于京都基因与基因组百科全书数据库，获得与造血相关的途径和靶点。通过蛋白质-蛋白质相互作用分析获得关键靶点。采用分子对接分析关键靶点与活性成分的结合能力。以骨髓细胞为实验模型验证药效。
从文献中检索到 CPL 的 139 种成分和 1868 个靶点。通过疾病富集分析，获得了 543 个出血性贫血靶点、223 个再生障碍性贫血靶点和 126 个镰状细胞贫血靶点。靶点器官富集得到骨髓的 27、29 和 20 个靶点。基于 KEGG 通路富集，共发现 47 个共享造血通路和 42 个相关靶点。关键靶点为血管内皮生长因子 A（VEGFA）、白细胞介素 10（IL-10）、血小板内皮细胞黏附分子-1（PECAM1）、C-C 基序趋化因子 2（CCL2）和血管细胞黏附分子 1（VCAM1）。CPL 的活性成分包括熊果酸、槲皮素和橙皮苷。CPL 处理后，VEGFA 的表达明显增加。槲皮素和熊果酸作用于 VEGFA。槲皮素和橙皮苷作用于 VCAM1。槲皮素作用于 IL-10、CCL2、VCAM1 和 VEGFA。细胞实验表明，CPL 可促进骨髓细胞的增殖和迁移。
CPL 通过多种成分、靶点和途径协同治疗贫血。
