Study on the Mechanism of Angiogenesis-Regulating Anti-Lung Cancer Action of Herbal Couple Curcumae Rhizoma-Sparganii Rhizoma Based on Network Pharmacology-Molecular Docking and Zebrafish Model
10.11842/wst.20240713002
- VernacularTitle:基于网络药理学-分子对接技术和斑马鱼模型探究莪术-三棱药对调控血管生成抗肺癌作用机制
- Author:
Mingxia LI
1
;
Weirui LIU
;
Mengyu SUN
;
Wei LIU
;
Xianxian LI
;
Xiuhuan WANG
;
Gaimei SHE
Author Information
1. 北京中医药大学中药学院 北京 100029
- Publication Type:Journal Article
- Keywords:
Curcumae Rhizoma-Sparganii Rhizoma;
Network pharmacology;
Molecular docking;
Zebrafish;
Angiogenesis;
Lung cancer
- From:
World Science and Technology-Modernization of Traditional Chinese Medicine
2025;27(5):1485-1500
- CountryChina
- Language:Chinese
-
Abstract:
Objective To predict the mechanism of herbal couple Curcumae Rhizoma-Sparganii Rhizoma(CR-SR)in modulation of angiogenesis against lung cancer based on network pharmacology and molecular docking technology,and validate by zebrafish model.Methods The active ingredients and potential targets for anti-lung cancer and antiangiogenesis of CR and SR were screened by network pharmacology.The targets were intersected with those screened from the OMIM database and GeneCards database for lung cancer and antiangiogenesis.Herbal couple-lung cancer and herbal couple-antiangiogenesis of protein-protein interaction(PPI)network was constructed by taking intersecting targets to screen the common and core targets of the herbal couple in lung cancer and anti-angiogenesis.Herbal couple-lung cancer and herbal couple-antiangiogenesis of Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses were performed by Metascape database.The binding ability and the amino acid residues involved of core targets to major components were evaluated by molecular docking technique.In vitro,CCK-8 method was applied to investigate the effects of herbal couple and single drugs on the cell viability of human umbilical vein endothelial cells(HUVECs).Zebrafish embryos were randomly divided into blank control group,different concentration of drug pairs and single drug group,and positive drug control group,and the number of intersegmental vessels of zebrafish in each group was counted after 72 hour.The mRNA expression levels of angiogenesis-related genes,VEGFA,VEGFR2,VEGFR3,EGFR,etc.,were detected by qRT-PCR.Results 106 herbal couple-lung cancer common targets and 130 herbal couple-antiangiogenesis common targets were screened by network pharmacology.Meanwhile,85 of targets were identical.GO function enrichment analyses of herbal couple-lung cancer resulted in 1648 GO analysis entries,KEGG pathway enrichment analyses resulted in 186 signaling pathways.GO function enrichment analyses herbal couple-antiangiogenesis resulted in 1844 GO analysis entries,KEGG pathway enrichment analyses resulted in 188 signaling pathways.The molecular docking results showed a better affinity between the target and the components,and the forces between them mainly included hydrogen bonding and hydrophobic interactions.In vitro cellular experiments demonstrated that the two drugs were used as a drug pair to enhance the inhibitory effect on the cell viability of HUVECs.The zebrafish experiments indicated that the toxicity order of herbal couple and single drugs was CR>CR-SR>SR.The results of transgenic zebrafish vascular fluorescence model confirmed that CR-SR and single drugs had anti-angiogenic activity,with the anti-angiogenic activity order of herbal couple and single drugs was CR-SR>SR>CR.The results of qRT-PCR showed that CR-SR drug pairs and single drugs significantly reduced the expression levels of angiogenesis-related genes VEGFA,VEGFR2,EGFR,MMP9,etc.,and had anti-angiogenic effects.Conclusion CR-SR and single drugs had anti-lung cancer effects on multiple identical targets and regulated multiple identical signaling pathways,and their combination had a synergistic effect.The treatment of lung cancer may be through the regulation of angiogenesis-related target VEGFA,VEGFR2,EGFR,etc.,in order to play an anti-angiogenic effect.
