Network Pharmacological Mechanism of Cinnamomi Ramulus-Radix Paeoniae Rubra Compatibility in Remodeling Tumor Vascular Microenvironment Based on Theory of Nutritive Qi and Defensive Qi
Network Pharmacological Mechanism of Cinnamomi Ramulus-Radix Paeoniae Rubra Compatibility in Remodeling Tumor Vascular Microenvironment Based on Theory of Nutritive Qi and Defensive Qi
OBJECTIVE:To probe into the predict the potential targets and pathways of Cinnamomi Ramulus-Radix Paeoniae Rubra compatibility affecting tumor angiogenesis by using network pharmacology,and to explore the network pharmacological mechanism of the compatible structure to remodel the tumor vascular microenvironment from the molecular network pharmacological level.METHODS:Chemical components and potential targets of Cinnamomi Ramulus and Radix Paeoniae Rubra were retrieved based on the traditional Chinese medicines systems pharmacology platform(TCMSP).Oral bioavailability≥30%and drug-like properties≥0.18 were selected as chemical composition screening conditions.The target of angiogenesis was searched in GeneCards database.Cytoscape 3.6.0 software was used to draw the network diagram of Cinnamomi Ramulus-Radix Paeoniae Rubra-compound-targets-angiogenesis.STRING 11.0 online software was used to construct the protein-protein Interaction(PPI)network and mine the core targets.Gene ontology(GO)function enrichment analysis and Kyoto Encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed for proteins in the potential target network of the compound active component by using David Bioinformatics Resources database.RESULTS:Totally 33 active components of Cinnamomi Ramulus-Radix Paeoniae Rubra were used in 77 targets of angiogenesis.Core targets of PPI network included protein kinase B(Akt)1,JUN,interleukin 6,matrix metalloproteinases,vascular endothelial growth factor A,nitric oxide synthase 2,and hypoxia-inducible factor-1α.GO functional enrichment analysis suggested that the key proteins of compatibility were mainly biological processes such as DNA-binding transcriptional activator activity,heme-binding activity,antioxidant activity,nuclear receptor activity and transcription factor activity.KEGG pathway enrichment analysis showed that the compatibility was involved in hypoxia-inducible factor-1(HIF-1)signaling pathway,p53 signaling pathway,apoptosis signaling pathway,epidermal growth factor receptor tyrosine kinase inhibitor resistance signaling pathway,vascular endothelial growth factor(VEGF)signaling pathway,and phosphatidylinositol 3-kinase-Akt signaling pathway,suggesting that Cinnamomi Ramulus-Radix Paeoniae Rubra compatibility was most closely related to tumor angiogenesis.CONCLUSIONS:Components such as baicalein,sitosterol and ellagic acid in Cinnamomi Ramulus-Radix Paeoniae Rubra compatibility may affect tumor angiogenesis and intervene in the biological behavior of tumors through the HIF-1 signaling pathway and VEGF signaling pathway.
关键词
营卫/桂枝/赤芍/配伍/肿瘤血管微环境/网络药理学
Key words
Theory of nutritive Qi and defensive Qi/Cinnamomi Ramulus/Radix Paeoniae Rubra/Compatibility/Tumor vascular microenvironment/Network pharmacology
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