Journal of Traditional Chinese Medicine ›› 2023, Vol. 43 ›› Issue (3): 542-551.DOI: 10.19852/j.cnki.jtcm.2023.03.004
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Mechanism underlying Fanmugua (Fructus Caricae) leaf multicomponent synergistic therapy for anemia: data mining based on hematopoietic network
JIA Lihong1,2, TIE Defu1, FAN Zhaohui1, CHEN Dan1, CHEN Qizhu1, CHEN Jun3, BO Huaben1(
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- 1 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
3 College of Pharmacy, Guangdong Pharmaceutical University, Guangdong 510006, China
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Received:2022-01-19Accepted:2022-04-18Online:2023-06-15Published:2023-04-28 -
Contact:BO Huaben, School of Bioscience and Biopharmaceutics, Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangdong 510006, China. bohuaben@gdpu.edu.cn. Telephone: +86-20-39352201 -
Supported by:Study on the Effect of Intestinal Bacteria on the Hematopoietic Component Absorption Mechanism of Danggui Buxue Tang(82104514);Based on the Multilevel Pharmacodynamic Model to Explore the Material Basis of Regulation of Erythroid Progenitor Cell Differentiation by Danggui Buxue Tang(201707010441);Innovation and University Promotion Project of Guangdong Pharmaceutical University(2017KCXTD020)
Cite this article
JIA Lihong, TIE Defu, FAN Zhaohui, CHEN Dan, CHEN Qizhu, CHEN Jun, BO Huaben. Mechanism underlying Fanmugua (Fructus Caricae) leaf multicomponent synergistic therapy for anemia: data mining based on hematopoietic network[J]. Journal of Traditional Chinese Medicine, 2023, 43(3): 542-551.
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Figure 1 Flowchart of a data integration strategy to investigate the pharmacologic mechanisms of CPL for the treatment of anemia CPL: Fanmugua (Fructus Caricae) Leaf; CNKI: China National Knowledge Infrastructure; SMILES: simplified molecular input line entry specification; TCMSP: Traditional Chinese Medicine Systems Pharmacology; SEA: Similarity ensemble Approach Search Server; STITCH: Search Tool for Interacting Chemicals; KEGG: Kyoto Encyclopedia of Genes and Genomes database; PDB: Protein Data Bank.
Figure 1 Flowchart of a data integration strategy to investigate the pharmacologic mechanisms of CPL for the treatment of anemia CPL: Fanmugua (Fructus Caricae) Leaf; CNKI: China National Knowledge Infrastructure; SMILES: simplified molecular input line entry specification; TCMSP: Traditional Chinese Medicine Systems Pharmacology; SEA: Similarity ensemble Approach Search Server; STITCH: Search Tool for Interacting Chemicals; KEGG: Kyoto Encyclopedia of Genes and Genomes database; PDB: Protein Data Bank.
Figure 2 Bioinformatics analysis of targets of CPL A: disease classification and target proportion; B, C, D: targets of hemorrhagic anemia (HA, B), aplastic anemia (AA, C), sickle cell anemia (SCA, D) enriched in bone, blood, liver, and kidney. The node represents the target organ or related target. The size of each node is proportional to the number of connections (degree). The closer the node is to the center, the more related target organs it represents, and nodes are labeled with the corresponding name. E: pathway-target interaction network. Green nodes represent pathways, and red nodes represent targets. If the target is associated with the pathway, it is linked in a straight line. The area of the pathway node is proportional to the number of pathways in which the target is involved. The letters are node labels. F: PPI analysis of targets in shared pathways. An edge represents an association between two proteins, and the area of a node is proportional to the total. CPL: Fanmugua (Fructus Caricae) Leaf; PPI: protein-protein interaction analysis.
Figure 2 Bioinformatics analysis of targets of CPL A: disease classification and target proportion; B, C, D: targets of hemorrhagic anemia (HA, B), aplastic anemia (AA, C), sickle cell anemia (SCA, D) enriched in bone, blood, liver, and kidney. The node represents the target organ or related target. The size of each node is proportional to the number of connections (degree). The closer the node is to the center, the more related target organs it represents, and nodes are labeled with the corresponding name. E: pathway-target interaction network. Green nodes represent pathways, and red nodes represent targets. If the target is associated with the pathway, it is linked in a straight line. The area of the pathway node is proportional to the number of pathways in which the target is involved. The letters are node labels. F: PPI analysis of targets in shared pathways. An edge represents an association between two proteins, and the area of a node is proportional to the total. CPL: Fanmugua (Fructus Caricae) Leaf; PPI: protein-protein interaction analysis.
Figure 3 Molecular docking between the anti-anemia target proteins and the active compound of CPL A: interaction of VEGFA and Ursolic acid. B: interaction of IL-10 and Quercetin. C: interaction of PECAM1 and Ursolic acid. D: interaction of CCL2 and Quercetin. E: interaction of VCAM1 and Hesperidin. The blue stick represents the active compound; the gray stick represents the local peptide chain of the target protein; and the colored thin line represents residue of the protein binding site and is labeled with the name. The dotted line represents the hydrogen bonds, and the number represents the interaction distance. VEGFA: vascular endothelial growth factor A; IL-10: interleukin 10; PECAM1: platelet endothelial cell adhesion molecule-1; CCL2: C-C motif chemokine 2; VCAM1: vascular cell adhesion molecule 1.
Figure 3 Molecular docking between the anti-anemia target proteins and the active compound of CPL A: interaction of VEGFA and Ursolic acid. B: interaction of IL-10 and Quercetin. C: interaction of PECAM1 and Ursolic acid. D: interaction of CCL2 and Quercetin. E: interaction of VCAM1 and Hesperidin. The blue stick represents the active compound; the gray stick represents the local peptide chain of the target protein; and the colored thin line represents residue of the protein binding site and is labeled with the name. The dotted line represents the hydrogen bonds, and the number represents the interaction distance. VEGFA: vascular endothelial growth factor A; IL-10: interleukin 10; PECAM1: platelet endothelial cell adhesion molecule-1; CCL2: C-C motif chemokine 2; VCAM1: vascular cell adhesion molecule 1.
Figure 4 Experimental validation of CPL in the treatment of anemia A, B: effect of CPL on erythroid related cells, comparison of proportion of EryA, EryB and EryC in erythrocytes in bone marrow with CPL treatment. (Erythrocyte = EryA + EryB + EryC, EryA: early-stage erythroid cells, FshighCD71highTER119high; EryB: middle-stage erythroid cells, FslowCD71highTER119high; EryC: late-stage erythroid cells, FslowCD71lowTER119high). Statistical analysis was performed by the method of unpaired t-test. Values are the mean ± standard deviation (n = 3). (aP<0.05 compared with the control group; t-test). C: effect of different concentrations of CPL on the proliferation of bone marrow cells; D: effects of CPL (1 mg/mL) on BMSC migration at 0 h, 48 h, and 72 h (magnification; 200×). Control groups: D1 (0 h), D2 (48 h) and D3 (72 h). CPL (1 mg/mL) groups: D4 (0 h), D5 (48 h) and D6 (72 h). E: migration rate of BMSCs was quantified using ImageJ software and statistical analysis was performed by the method of unpaired t-test. F: expression levels of key target genes were evaluated by qPCR. CPL: Fanmugua (Fructus Caricae) Leaf; EryA: early-stage erythroid cells; EryB: middle-stage erythroid cells; EryA: late-stage erythroid cells; VEGFA: vascular endothelial growth factor A; IL-10: interleukin 10; PECAM1: platelet-endothelial cell adhesion molecule-1; CCL2: C-C motif chemokine 2; VCAM1: vascular cell adhesion molecule 1; qPCR: quantitative polymerase chain reaction. Values are the mean ± standard deviation (n = 3). bP<0.05, compared to the control group; cP<0.05, compared to the control group; dP<0.01, compared to the respective control group; eP<0.05, compared to the control group; t-test).
Figure 4 Experimental validation of CPL in the treatment of anemia A, B: effect of CPL on erythroid related cells, comparison of proportion of EryA, EryB and EryC in erythrocytes in bone marrow with CPL treatment. (Erythrocyte = EryA + EryB + EryC, EryA: early-stage erythroid cells, FshighCD71highTER119high; EryB: middle-stage erythroid cells, FslowCD71highTER119high; EryC: late-stage erythroid cells, FslowCD71lowTER119high). Statistical analysis was performed by the method of unpaired t-test. Values are the mean ± standard deviation (n = 3). (aP<0.05 compared with the control group; t-test). C: effect of different concentrations of CPL on the proliferation of bone marrow cells; D: effects of CPL (1 mg/mL) on BMSC migration at 0 h, 48 h, and 72 h (magnification; 200×). Control groups: D1 (0 h), D2 (48 h) and D3 (72 h). CPL (1 mg/mL) groups: D4 (0 h), D5 (48 h) and D6 (72 h). E: migration rate of BMSCs was quantified using ImageJ software and statistical analysis was performed by the method of unpaired t-test. F: expression levels of key target genes were evaluated by qPCR. CPL: Fanmugua (Fructus Caricae) Leaf; EryA: early-stage erythroid cells; EryB: middle-stage erythroid cells; EryA: late-stage erythroid cells; VEGFA: vascular endothelial growth factor A; IL-10: interleukin 10; PECAM1: platelet-endothelial cell adhesion molecule-1; CCL2: C-C motif chemokine 2; VCAM1: vascular cell adhesion molecule 1; qPCR: quantitative polymerase chain reaction. Values are the mean ± standard deviation (n = 3). bP<0.05, compared to the control group; cP<0.05, compared to the control group; dP<0.01, compared to the respective control group; eP<0.05, compared to the control group; t-test).
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