|Table of Contents|

Mechanism of Qinghao Biejia Decoction in treatment of angiogenesis based on network pharmacology and animal experimental verification

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 08
Page:
1404-1413
Research Field:
Publishing date:

Info

Title:
Mechanism of Qinghao Biejia Decoction in treatment of angiogenesis based on network pharmacology and animal experimental verification
Author(s):
LI Yan1; 2; LI Xiao1; LIU Yanjun1; GAO Peng3; GUO Ping1
1.School of Traditional Chinese Medicine;2.School of Nursing,Shandong University of Traditional Chinese Medicine,Shandong Jinan 250355,China;3.the First Affiliated Hospital of Shandong First Medical University,Shandong Jinan 250014,China.
Keywords:
Qinghao Biejia Decoction; angiogenesis; network pharmacology; vascular endothelial growth factor; signal transducer and activator of transcription 3; Lewis lung carcinoma
PACS:
R73-3
DOI:
10.3969/j.issn.1672-4992.2023.08.005
Abstract:
Objective:To explore the underlying molecular mechanism of Qinghao Biejia Decoction on angiogenesis based on network pharmacology,and to validate the STAT3/VEGF pathway in Lewis lung carcinoma mouse graft tumor model.Methods:The main active ingredients of Qinghao Biejia Decoction were selected from TCMSP,BATMAN-TCM and literatures,and the target genes of ingredients were predicted by Swiss Target Prediction platform.The target genes related to angiogenesis were collected by three disease databases such as GeneCards,OMIM and TTD.After taking the intersection,STRING database and Cytoscape 3.7.1 software were used to construct protein-protein interaction (PPI) network and select key target genes.The Metascape platform was used to perform gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis for hub genes.In animal experiment,C57BL/6J male mice were seeded with Lewis lung carcinoma cells to establish a subcutaneous tumor graft model.Tumor-bearing mice were randomly divided into Control group,Qinghao Biejia Decoction high-dose (16.0 g/kg),medium-dose (8.0 g/kg),low-dose (4.0 g/kg) group and bevacizumab (15 mg/kg) group.The administration and model groups were infused with Qinghao Biejia Decoction or intraperitoneal injection with bevacizumab.After the end of the drug administration,the subcutaneous tumor tissues were collected.The tumor weight was assessed,and the tumor volume and tumor-inhibition rate were calculated.The expression of endothelial cell marker CD31 was measured by immunohistochemistry,and the microvascular density (MVD) was calculated.Tumor histopathological change was observed by HE staining,and protein expression levels of pSTAT3,STAT3 and VEGF were detected by Western blot.Results:A total of 61 active ingredients and 523 drug-related target genes,1 229 angiogenesis-related target genes,176 intersection target genes and 22 key target genes were obtained.VEGF was the first key target gene of the antiangiogenic effect exerting by Qinghao Biejia Decoction,and the signaling pathways were mainly cancer-related signaling pathways,such as HIF-1,VEGF and JAK-STAT.Animal experiments showed that compared with the Control group,the tumor weight and tumor volume in Qinghao Biejia Decoction high-dose and medium-dose group were decreased (P＜0.05，P＜0.01),and MVD in high-dose group was decreased (P＜0.01).The tumor cells shrinkage,pyknosis,karyorrhexis,hemorrhage and necrosis were more seen in administration group.The expression levels of VEGF,pSTAT3 protein and the proportion of pSTAT3 to total STAT3 were significantly reduced in high-dose group (P＜0.05).Although the expression levels of VEGF and pSTAT3 proteins in the medium-dose and low-dose group showed a downward trend,the difference was not statistically significant.Conclusion:Qinghao Biejia Decoction can inhibit angiogenesis through multi-component-target-pathway,and the underlying mechanism may be related to the inhibition of STAT3/VEGF signaling.

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Memo

Memo:
山东省中医药科技发展计划项目（编号：2019-0370）；山东省医药卫生科技发展计划项目(编号：2018WS260)；山东中医药大学青年科研创新团队（编号：［2020］54 号）
Last Update: 1900-01-01