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Integrated network pharmacology and serum metabolomics approach deciphers the anti-colon cancer mechanisms of Huangqi Guizhi Wuwu Decoction.

Authors :
Boyu Pan
Yafei Xia
Senbiao Fang
Jun Ai
Kunpeng Wang
Jian Zhang
Chunshuang Du
Yuzhou Chen
Liren Liu
Shu Yan
Source :
Frontiers in Pharmacology; 10/13/2022, Vol. 13, p1-21, 21p
Publication Year :
2022

Abstract

Huangqi Guizhi Wuwu Decoction (HGWD), as a classic Chinese herbal decoction, has been widely used in treating various diseases for hundreds of years. However, systematically elucidating its mechanisms of action remains a great challenge to the field. In this study, taking advantage of the network pharmacology approach, we discovered a potential new use of HGWD for patients with colon cancer (CC). Our in vivo result showed that orally administered HGWD markedly inhibited the growth of CC xenografts in mice. The subsequent enrichment analyses for the core therapeutic targets revealed that HGWD could affect multiple biological processes involving CC growth, such as metabolic reprogramming, apoptosis and immune regulation, through inhibiting multiple cell survival-related signalings, including MAPK and PI3K-AKT pathways. Notably, these in silico analysis results were most experimentally verified by a series of in vitro assays. Furthermore, our results based on serum metabolomics showed that the lipid metabolic pathways, including fatty acid biosynthesis and cholesterol metabolism, play key roles in delivery of the anti-CC effect of HGWD on tumor-bearing mice, and that cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a potential therapeutic target. Together, our integrated approach reveals a therapeutic effect of HGWDon CC, providing a valuable insight into developing strategies to predict and interpret the mechanisms of action for Chinese herbal decoctions. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16639812
Volume :
13
Database :
Complementary Index
Journal :
Frontiers in Pharmacology
Publication Type :
Academic Journal
Accession number :
159923968
Full Text :
https://doi.org/10.3389/fphar.2022.1043252