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Active compounds and underlying mechanisms of Scutellariae Barbatae Herba against pancreatic cancer based on network pharmacology and molecular experimental validation / 中草药
Chinese Traditional and Herbal Drugs ; (24): 3234-3245, 2020.
Article in Chinese | WPRIM | ID: wpr-846361
ABSTRACT

Objective:

To probe active components of Scutellariae Barbatae Herba (SBH) and its underlying complex mechanism in treating pancreatic cancer based on network pharmacology and molecular experimental validation.

Methods:

Active compounds of SBH and potential targets of these compounds were screened via Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Then the pancreatic cancer target database was established by using Comparative Toxicogenomics Database (CTD), Therapeutic Target Database (TTD), and Pharmacogenomics Knowledgebase (PharmGKB). Based on the matching results between SBH potential targets and pancreatic cancer targets, a PPI network was structured and then the hub targets were screened by using topology analysis. Furthermore, DAVID bioinformatics was utilized for both Gene ontoloty (GO) functional enrichment analysis and KEGG pathway enrichment analysis. At last, Western blotting was used to validate the regulating function of luteolin on P53, Bax and Bcl-2 targets of PANC-1 cells.

Results:

A total of 28 active ingredients including quercetin, luteolin and wogonin were screened out, and 24 hub targets of 91 targets including TP53, AKT1, JUN and VEGF were obtained. The results of DAVID enrichment analysis indicated that 73 cellular biological processes and 18 pathways were found to participate in the treatment of pancreatic cancer, mainly involving in regulating inflammatory microenvironment, cell cycle arrest, pro-apoptosis and anti-angiogenesis through NF-κB, p53, PI3K-AKT and VEGF signal pathways. Luteolin from SBH was validated to regulate key targets in the p53 signaling pathway to play a role in pro-apoptosis, which proved the reliability of results of network pharmacology.

Conclusion:

This study confirmed the synergistic effect of multiple component-multiple target-multiple pathway of SBH on the treatment of pancreatic cancer, which offered a theory for its clinical application.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Traditional and Herbal Drugs Year: 2020 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Traditional and Herbal Drugs Year: 2020 Type: Article