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Danggui Buxue Decoction in the Treatment of Metastatic Colon Cancer: Network Pharmacology Analysis and Experimental Validation

Authors Feng SH, Zhao B, Zhan X, Motanyane R, Wang SM, Li A

Received 20 November 2020

Accepted for publication 29 January 2021

Published 24 February 2021 Volume 2021:15 Pages 705—720

DOI https://doi.org/10.2147/DDDT.S293046

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Anastasios Lymperopoulos


Shi-Han Feng,1,* Bin Zhao,1,* Xue Zhan,2 Retsepile Motanyane,2 Shu-Mei Wang,2 Ao Li3

1Yong Chuan Hospital of Chongqing Medical University, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 2College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing, People’s Republic of China; 3Yong Chuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Shu-Mei Wang
College of Traditional Chinese Medicine, Chongqing Medical University, No. 1 Medical College Road, Chongqing, 400016, People’s Republic of China
Tel +86-18716369329
Email wangshumei@cqmu.edu.cn
Ao Li
Yong Chuan Hospital of Chongqing Medical University, NO. 439 Xuan Hua Road, Yongchuan District, Chongqing, 402160, People’s Republic of China
Tel +86-18580779649
Email wo_shi_li_ao_2@163.com

Purpose: This study aimed to reveal Danggui Buxue Decoction (DBD) candidate targets and mechanisms in the treatment of metastatic colon cancer (MCC), using network pharmacology-based analyses and experimental validation.
Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) database query and text mining were used to screen active compounds in DBD, and the Swiss target prediction platform was applied to predict compound-related target proteins. Targets likely associated with MCC were determined using GeneCards and OMIM databases. Targets common to DBD and MCC were obtained from the Venn platform; subsequently, Cytoscape was used to construct drug-compound-target-disease and protein-protein interaction networks. The hub gene was determined by R, while GO and KEGG enrichment analyses were performed on common targets to elucidate biological processes and signaling pathways involved in DBD against MCC. Finally, the metastatic colon cancer mouse model was used to detect the levels of expression of protein Bax, Bcl2, Caspase3, and Cleaved caspase3 by Western blot.
Results: A total of 28 active compounds and 61 common targets were predicted. The main compounds were quercetin, hederagenin, jaranol, methylnissolin, formononetin, calycosin, kaempferol, 3.9-di-O-methylnissolin, 24-propylcholesterol, and 7-O-methylisomucronulatol, present in Astragalus membranaceus (Huangqi, HQ). In addition, beta-sitosterol, ferulic acid, and stigmasterol, present in Angelica sinensis (Danggui, DG), were detected. JUN, PTSG2, EGFR, ESR1and, CASP3 genes were the top 5 hub genes in the PPI network. GO and KEGG enrichment analyses indicated that apoptosis played a major role in the biological processes and signaling pathways involved. Moreover, the in vivo experiment revealed that DBD inhibited MCC by up-regulating the expression of Bax, Caspase3, and Cleaved caspase3, and by down-regulating the expression of Bcl2.
Conclusion: This study revealed candidate DBD targets and mechanisms in the treatment of MCC, using network pharmacology-based analyses and experimental validation. The present findings provide a reference for tumor treatment during the perioperative period.

Keywords: Danggui Buxue Decoction, network pharmacology, primary tumor, metastatic tumor, perioperative period

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