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A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer

Danggui Sini Decoction (DSD), a classic Chinese herb medicine (CHM) formula, has been used to treat various diseases in China for centuries. However, it remains challenging to reveal its mechanism of action through conventional pharmacological methods. Here, we first explored the mechanism of action...

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Autores principales: Pan, Boyu, Wang, Yun, Wu, Chunnuan, Jia, Junrong, Huang, Chen, Fang, Senbiao, Liu, Liren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830678/
https://www.ncbi.nlm.nih.gov/pubmed/33505310
http://dx.doi.org/10.3389/fphar.2020.592903
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author Pan, Boyu
Wang, Yun
Wu, Chunnuan
Jia, Junrong
Huang, Chen
Fang, Senbiao
Liu, Liren
author_facet Pan, Boyu
Wang, Yun
Wu, Chunnuan
Jia, Junrong
Huang, Chen
Fang, Senbiao
Liu, Liren
author_sort Pan, Boyu
collection PubMed
description Danggui Sini Decoction (DSD), a classic Chinese herb medicine (CHM) formula, has been used to treat various diseases in China for centuries. However, it remains challenging to reveal its mechanism of action through conventional pharmacological methods. Here, we first explored the mechanism of action of DSD with the assistance of network pharmacology and bioinformatic analysis tools, and found a potential therapeutic effect of DSD on cancer. Indeed, our in vivo experiment demonstrated that oral administration of DSD could significantly inhibit the growth of xenografted gastric cancer (GC) on mice. The subsequent enrichment analyses for 123 candidate core targets evacuated from the drug/disease-target protein-protein interaction network showed that DSD could affect the key biological processes involving the survival and growth of GC cells, such as apoptosis and cell cycle, and the disturbance of these biological processes is likely attributed to the simultaneous inhibition of multiple signaling pathways, including PI3K/Akt, MAPK, and p53 pathways. Notably, these in silico results were further validated by a series of cellular functional and molecular biological assays in vitro. Moreover, molecular docking analysis suggested an important role of MCM2 in delivering the pharmacological activity of DSD against GC. Together, these results indicate that our network pharmacology and bioinformatics-guided approach is feasible and useful in exploring not only the mechanism of action, but also the “new use” of the old CHM formula.
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spelling pubmed-78306782021-01-26 A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer Pan, Boyu Wang, Yun Wu, Chunnuan Jia, Junrong Huang, Chen Fang, Senbiao Liu, Liren Front Pharmacol Pharmacology Danggui Sini Decoction (DSD), a classic Chinese herb medicine (CHM) formula, has been used to treat various diseases in China for centuries. However, it remains challenging to reveal its mechanism of action through conventional pharmacological methods. Here, we first explored the mechanism of action of DSD with the assistance of network pharmacology and bioinformatic analysis tools, and found a potential therapeutic effect of DSD on cancer. Indeed, our in vivo experiment demonstrated that oral administration of DSD could significantly inhibit the growth of xenografted gastric cancer (GC) on mice. The subsequent enrichment analyses for 123 candidate core targets evacuated from the drug/disease-target protein-protein interaction network showed that DSD could affect the key biological processes involving the survival and growth of GC cells, such as apoptosis and cell cycle, and the disturbance of these biological processes is likely attributed to the simultaneous inhibition of multiple signaling pathways, including PI3K/Akt, MAPK, and p53 pathways. Notably, these in silico results were further validated by a series of cellular functional and molecular biological assays in vitro. Moreover, molecular docking analysis suggested an important role of MCM2 in delivering the pharmacological activity of DSD against GC. Together, these results indicate that our network pharmacology and bioinformatics-guided approach is feasible and useful in exploring not only the mechanism of action, but also the “new use” of the old CHM formula. Frontiers Media S.A. 2021-01-11 /pmc/articles/PMC7830678/ /pubmed/33505310 http://dx.doi.org/10.3389/fphar.2020.592903 Text en Copyright © 2021 Pan, Wang, Wu, Jia, Huang, Fang and Liu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Pan, Boyu
Wang, Yun
Wu, Chunnuan
Jia, Junrong
Huang, Chen
Fang, Senbiao
Liu, Liren
A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer
title A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer
title_full A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer
title_fullStr A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer
title_full_unstemmed A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer
title_short A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer
title_sort mechanism of action study on danggui sini decoction to discover its therapeutic effect on gastric cancer
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830678/
https://www.ncbi.nlm.nih.gov/pubmed/33505310
http://dx.doi.org/10.3389/fphar.2020.592903
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