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The Synergistic Effects of 5-Aminosalicylic Acid and Vorinostat in the Treatment of Ulcerative Colitis

Background: The drug 5-aminosalicylic acid (5-ASA) is the first-line therapy for the treatment of patients with mild-to-moderate ulcerative colitis (UC). However, in some cases, 5-ASA cannot achieve the desired therapeutic effects. Therefore, patients have to undergo therapies that include corticost...

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Autores principales: He, Long, Wen, Shuting, Zhong, Zhuotai, Weng, Senhui, Jiang, Qilong, Mi, Hong, Liu, Fengbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176098/
https://www.ncbi.nlm.nih.gov/pubmed/34093178
http://dx.doi.org/10.3389/fphar.2021.625543
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author He, Long
Wen, Shuting
Zhong, Zhuotai
Weng, Senhui
Jiang, Qilong
Mi, Hong
Liu, Fengbin
author_facet He, Long
Wen, Shuting
Zhong, Zhuotai
Weng, Senhui
Jiang, Qilong
Mi, Hong
Liu, Fengbin
author_sort He, Long
collection PubMed
description Background: The drug 5-aminosalicylic acid (5-ASA) is the first-line therapy for the treatment of patients with mild-to-moderate ulcerative colitis (UC). However, in some cases, 5-ASA cannot achieve the desired therapeutic effects. Therefore, patients have to undergo therapies that include corticosteroids, monoclonal antibodies or immunosuppressants, which are expensive and may be accompanied by significant side effects. Synergistic drug combinations can achieve greater therapeutic effects than individual drugs while contributing to combating drug resistance and lessening toxic side effects. Thus, in this study, we sought to identify synergistic drugs that can act synergistically with 5-ASA. Methods: We started our study with protein-metabolite analysis based on peroxisome proliferator-activated receptor gamma (PPARG), the therapeutic target of 5-ASA, to identify more additional potential drug targets. Then, we further evaluated the possibility of their synergy with PPARG by integrating Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis, pathway-pathway interaction analysis, and semantic similarity analysis. Finally, we validated the synergistic effects with in vitro and in vivo experiments. Results: The combination of 5-ASA and vorinostat (SAHA) showed lower toxicity and mRNA expression of p65 in human colonic epithelial cell lines (Caco-2 and HCT-116), and more efficiently alleviated the symptoms of dextran sulfate sodium (DSS)-induced colitis than treatment with 5-ASA and SAHA alone. Conclusion: SAHA can exert effective synergistic effects with 5-ASA in the treatment of UC. One possible mechanism of synergism may be synergistic inhibition of the nuclear factor kappa B (NF-kB) signaling pathway. Moreover, the metabolite-butyric acid may be involved.
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spelling pubmed-81760982021-06-05 The Synergistic Effects of 5-Aminosalicylic Acid and Vorinostat in the Treatment of Ulcerative Colitis He, Long Wen, Shuting Zhong, Zhuotai Weng, Senhui Jiang, Qilong Mi, Hong Liu, Fengbin Front Pharmacol Pharmacology Background: The drug 5-aminosalicylic acid (5-ASA) is the first-line therapy for the treatment of patients with mild-to-moderate ulcerative colitis (UC). However, in some cases, 5-ASA cannot achieve the desired therapeutic effects. Therefore, patients have to undergo therapies that include corticosteroids, monoclonal antibodies or immunosuppressants, which are expensive and may be accompanied by significant side effects. Synergistic drug combinations can achieve greater therapeutic effects than individual drugs while contributing to combating drug resistance and lessening toxic side effects. Thus, in this study, we sought to identify synergistic drugs that can act synergistically with 5-ASA. Methods: We started our study with protein-metabolite analysis based on peroxisome proliferator-activated receptor gamma (PPARG), the therapeutic target of 5-ASA, to identify more additional potential drug targets. Then, we further evaluated the possibility of their synergy with PPARG by integrating Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis, pathway-pathway interaction analysis, and semantic similarity analysis. Finally, we validated the synergistic effects with in vitro and in vivo experiments. Results: The combination of 5-ASA and vorinostat (SAHA) showed lower toxicity and mRNA expression of p65 in human colonic epithelial cell lines (Caco-2 and HCT-116), and more efficiently alleviated the symptoms of dextran sulfate sodium (DSS)-induced colitis than treatment with 5-ASA and SAHA alone. Conclusion: SAHA can exert effective synergistic effects with 5-ASA in the treatment of UC. One possible mechanism of synergism may be synergistic inhibition of the nuclear factor kappa B (NF-kB) signaling pathway. Moreover, the metabolite-butyric acid may be involved. Frontiers Media S.A. 2021-05-21 /pmc/articles/PMC8176098/ /pubmed/34093178 http://dx.doi.org/10.3389/fphar.2021.625543 Text en Copyright © 2021 He, Wen, Zhong, Weng, Jiang, Mi and Liu. 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
He, Long
Wen, Shuting
Zhong, Zhuotai
Weng, Senhui
Jiang, Qilong
Mi, Hong
Liu, Fengbin
The Synergistic Effects of 5-Aminosalicylic Acid and Vorinostat in the Treatment of Ulcerative Colitis
title The Synergistic Effects of 5-Aminosalicylic Acid and Vorinostat in the Treatment of Ulcerative Colitis
title_full The Synergistic Effects of 5-Aminosalicylic Acid and Vorinostat in the Treatment of Ulcerative Colitis
title_fullStr The Synergistic Effects of 5-Aminosalicylic Acid and Vorinostat in the Treatment of Ulcerative Colitis
title_full_unstemmed The Synergistic Effects of 5-Aminosalicylic Acid and Vorinostat in the Treatment of Ulcerative Colitis
title_short The Synergistic Effects of 5-Aminosalicylic Acid and Vorinostat in the Treatment of Ulcerative Colitis
title_sort synergistic effects of 5-aminosalicylic acid and vorinostat in the treatment of ulcerative colitis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176098/
https://www.ncbi.nlm.nih.gov/pubmed/34093178
http://dx.doi.org/10.3389/fphar.2021.625543
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