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In Silico and In Vivo Studies on the Mechanisms of Chinese Medicine Formula (Gegen Qinlian Decoction) in the Treatment of Ulcerative Colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, and Gegen Qinlian Decoction (GQD), a Chinese botanical formula, has exhibited beneficial efficacy against UC. However, the mechanisms underlying the effect of GQD still remain to be elucidated. In this study, network pharmacology appro...

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Autores principales: Liu, Xiaolu, Fan, Yuling, Du, Lipeng, Mei, Zhigang, Fu, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232523/
https://www.ncbi.nlm.nih.gov/pubmed/34177580
http://dx.doi.org/10.3389/fphar.2021.665102
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author Liu, Xiaolu
Fan, Yuling
Du, Lipeng
Mei, Zhigang
Fu, Yang
author_facet Liu, Xiaolu
Fan, Yuling
Du, Lipeng
Mei, Zhigang
Fu, Yang
author_sort Liu, Xiaolu
collection PubMed
description Ulcerative colitis (UC) is a chronic inflammatory bowel disease, and Gegen Qinlian Decoction (GQD), a Chinese botanical formula, has exhibited beneficial efficacy against UC. However, the mechanisms underlying the effect of GQD still remain to be elucidated. In this study, network pharmacology approach and molecular docking in silico were applied to uncover the potential multicomponent synergetic effect and molecular mechanisms. The targets of ingredients in GQD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM) database, while the UC targets were retrieved from Genecards, therapeutic target database (TTD) and Online Mendelian Inheritance in Man (OMIM) database. The topological parameters of Protein-Protein Interaction (PPI) data were used to screen the hub targets in the network. The possible mechanisms were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was used to verify the binding affinity between the active compounds and hub targets. Network pharmacology analysis successfully identified 77 candidate compounds and 56 potential targets. The targets were further mapped to 20 related pathways to construct a compound-target-pathway network and an integrated network of GQD treating UC. Among these pathways, PI3K-AKT, HIF-1, VEGF, Ras, and TNF signaling pathways may exert important effects in the treatment of UC via inflammation suppression and anti-carcinogenesis. In the animal experiment, treatment with GQD and sulfasalazine (SASP) both ameliorated inflammation in UC. The proinflammatory cytokines (TNF-α, IL-1β, and IL-6) induced by UC were significantly decreased by GQD and SASP. Moreover, the protein expression of EGFR, PI3K, and phosphorylation of AKT were reduced after GQD and SASP treatment, and there was no significance between the GQD group and SASP group. Our study systematically dissected the molecular mechanisms of GQD on the treatment of UC using network pharmacology, as well as uncovered the therapeutic effects of GQD against UC through ameliorating inflammation via downregulating EGFR/PI3K/AKT signaling pathway and the pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6.
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spelling pubmed-82325232021-06-26 In Silico and In Vivo Studies on the Mechanisms of Chinese Medicine Formula (Gegen Qinlian Decoction) in the Treatment of Ulcerative Colitis Liu, Xiaolu Fan, Yuling Du, Lipeng Mei, Zhigang Fu, Yang Front Pharmacol Pharmacology Ulcerative colitis (UC) is a chronic inflammatory bowel disease, and Gegen Qinlian Decoction (GQD), a Chinese botanical formula, has exhibited beneficial efficacy against UC. However, the mechanisms underlying the effect of GQD still remain to be elucidated. In this study, network pharmacology approach and molecular docking in silico were applied to uncover the potential multicomponent synergetic effect and molecular mechanisms. The targets of ingredients in GQD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM) database, while the UC targets were retrieved from Genecards, therapeutic target database (TTD) and Online Mendelian Inheritance in Man (OMIM) database. The topological parameters of Protein-Protein Interaction (PPI) data were used to screen the hub targets in the network. The possible mechanisms were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was used to verify the binding affinity between the active compounds and hub targets. Network pharmacology analysis successfully identified 77 candidate compounds and 56 potential targets. The targets were further mapped to 20 related pathways to construct a compound-target-pathway network and an integrated network of GQD treating UC. Among these pathways, PI3K-AKT, HIF-1, VEGF, Ras, and TNF signaling pathways may exert important effects in the treatment of UC via inflammation suppression and anti-carcinogenesis. In the animal experiment, treatment with GQD and sulfasalazine (SASP) both ameliorated inflammation in UC. The proinflammatory cytokines (TNF-α, IL-1β, and IL-6) induced by UC were significantly decreased by GQD and SASP. Moreover, the protein expression of EGFR, PI3K, and phosphorylation of AKT were reduced after GQD and SASP treatment, and there was no significance between the GQD group and SASP group. Our study systematically dissected the molecular mechanisms of GQD on the treatment of UC using network pharmacology, as well as uncovered the therapeutic effects of GQD against UC through ameliorating inflammation via downregulating EGFR/PI3K/AKT signaling pathway and the pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6. Frontiers Media S.A. 2021-06-11 /pmc/articles/PMC8232523/ /pubmed/34177580 http://dx.doi.org/10.3389/fphar.2021.665102 Text en Copyright © 2021 Liu, Fan, Du, Mei and Fu. https://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
Liu, Xiaolu
Fan, Yuling
Du, Lipeng
Mei, Zhigang
Fu, Yang
In Silico and In Vivo Studies on the Mechanisms of Chinese Medicine Formula (Gegen Qinlian Decoction) in the Treatment of Ulcerative Colitis
title In Silico and In Vivo Studies on the Mechanisms of Chinese Medicine Formula (Gegen Qinlian Decoction) in the Treatment of Ulcerative Colitis
title_full In Silico and In Vivo Studies on the Mechanisms of Chinese Medicine Formula (Gegen Qinlian Decoction) in the Treatment of Ulcerative Colitis
title_fullStr In Silico and In Vivo Studies on the Mechanisms of Chinese Medicine Formula (Gegen Qinlian Decoction) in the Treatment of Ulcerative Colitis
title_full_unstemmed In Silico and In Vivo Studies on the Mechanisms of Chinese Medicine Formula (Gegen Qinlian Decoction) in the Treatment of Ulcerative Colitis
title_short In Silico and In Vivo Studies on the Mechanisms of Chinese Medicine Formula (Gegen Qinlian Decoction) in the Treatment of Ulcerative Colitis
title_sort in silico and in vivo studies on the mechanisms of chinese medicine formula (gegen qinlian decoction) in the treatment of ulcerative colitis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232523/
https://www.ncbi.nlm.nih.gov/pubmed/34177580
http://dx.doi.org/10.3389/fphar.2021.665102
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