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Systems pharmacology approach reveals the antiinflammatory effects of Ampelopsis grossedentata on dextran sodium sulfate-induced colitis
AIM: To investigate the protective effects of Ampelopsis grossedentata (AMP) on dextran sulfate sodium (DSS)-induced colitis in mice based on systems pharmacology approach. METHODS: Systems pharmacology approach was used to predict the active ingredients, candidate targets and the efficacy of AMP on...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889820/ https://www.ncbi.nlm.nih.gov/pubmed/29632421 http://dx.doi.org/10.3748/wjg.v24.i13.1398 |
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author | Chen, You-Lan Zhang, Ya-Li Dai, Yan-Cheng Tang, Zhi-Peng |
author_facet | Chen, You-Lan Zhang, Ya-Li Dai, Yan-Cheng Tang, Zhi-Peng |
author_sort | Chen, You-Lan |
collection | PubMed |
description | AIM: To investigate the protective effects of Ampelopsis grossedentata (AMP) on dextran sulfate sodium (DSS)-induced colitis in mice based on systems pharmacology approach. METHODS: Systems pharmacology approach was used to predict the active ingredients, candidate targets and the efficacy of AMP on ulcerative colitis (UC) using a holistic process of active compound screening, target fishing, network construction and analysis. A DSS-induced colitis model in C57BL/6 mice (n = 10/group) was constructed and treated with 5-aminosalicylic acid (100 mg/kg/d) and AMP (400 mg/kg/d) to confirm the underlying mechanisms and effects of AMP on UC with western blot analyses, polymerase chain reaction, histological staining and immunohistochemistry. RESULTS: The therapeutic effects of AMP against DSS-induced colitis were determined in the beginning, and the results showed that AMP significantly improved the disease in general observations and histopathology analysis. Subsequent systems pharmacology predicted 89 corresponding targets for the four candidate compounds of AMP, as well as 123 candidate targets of UC, and protein-protein interaction networks were constructed for the interaction of putative targets of AMP against UC. Enrichment analyses on TNF-α and RANKL/RANK, a receptor activator of NF-κB signaling pathways, were then carried out. Experimental validation revealed that inflammation-related signaling pathways were activated in the DSS group, and AMP significantly suppressed DSS-induced high expression of IRAK1, TRAF6, IκB and NF-κB, and inhibited the elevated expression levels of TNF-α, IL-1β, IL-6 and IL-8. CONCLUSION: AMP could exert protective effects on UC via suppressing the IRAK1/TRAF6/NF-κB-mediated inflammatory signaling pathways. |
format | Online Article Text |
id | pubmed-5889820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-58898202018-04-09 Systems pharmacology approach reveals the antiinflammatory effects of Ampelopsis grossedentata on dextran sodium sulfate-induced colitis Chen, You-Lan Zhang, Ya-Li Dai, Yan-Cheng Tang, Zhi-Peng World J Gastroenterol Basic Study AIM: To investigate the protective effects of Ampelopsis grossedentata (AMP) on dextran sulfate sodium (DSS)-induced colitis in mice based on systems pharmacology approach. METHODS: Systems pharmacology approach was used to predict the active ingredients, candidate targets and the efficacy of AMP on ulcerative colitis (UC) using a holistic process of active compound screening, target fishing, network construction and analysis. A DSS-induced colitis model in C57BL/6 mice (n = 10/group) was constructed and treated with 5-aminosalicylic acid (100 mg/kg/d) and AMP (400 mg/kg/d) to confirm the underlying mechanisms and effects of AMP on UC with western blot analyses, polymerase chain reaction, histological staining and immunohistochemistry. RESULTS: The therapeutic effects of AMP against DSS-induced colitis were determined in the beginning, and the results showed that AMP significantly improved the disease in general observations and histopathology analysis. Subsequent systems pharmacology predicted 89 corresponding targets for the four candidate compounds of AMP, as well as 123 candidate targets of UC, and protein-protein interaction networks were constructed for the interaction of putative targets of AMP against UC. Enrichment analyses on TNF-α and RANKL/RANK, a receptor activator of NF-κB signaling pathways, were then carried out. Experimental validation revealed that inflammation-related signaling pathways were activated in the DSS group, and AMP significantly suppressed DSS-induced high expression of IRAK1, TRAF6, IκB and NF-κB, and inhibited the elevated expression levels of TNF-α, IL-1β, IL-6 and IL-8. CONCLUSION: AMP could exert protective effects on UC via suppressing the IRAK1/TRAF6/NF-κB-mediated inflammatory signaling pathways. Baishideng Publishing Group Inc 2018-04-07 2018-04-07 /pmc/articles/PMC5889820/ /pubmed/29632421 http://dx.doi.org/10.3748/wjg.v24.i13.1398 Text en ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
spellingShingle | Basic Study Chen, You-Lan Zhang, Ya-Li Dai, Yan-Cheng Tang, Zhi-Peng Systems pharmacology approach reveals the antiinflammatory effects of Ampelopsis grossedentata on dextran sodium sulfate-induced colitis |
title | Systems pharmacology approach reveals the antiinflammatory effects of Ampelopsis grossedentata on dextran sodium sulfate-induced colitis |
title_full | Systems pharmacology approach reveals the antiinflammatory effects of Ampelopsis grossedentata on dextran sodium sulfate-induced colitis |
title_fullStr | Systems pharmacology approach reveals the antiinflammatory effects of Ampelopsis grossedentata on dextran sodium sulfate-induced colitis |
title_full_unstemmed | Systems pharmacology approach reveals the antiinflammatory effects of Ampelopsis grossedentata on dextran sodium sulfate-induced colitis |
title_short | Systems pharmacology approach reveals the antiinflammatory effects of Ampelopsis grossedentata on dextran sodium sulfate-induced colitis |
title_sort | systems pharmacology approach reveals the antiinflammatory effects of ampelopsis grossedentata on dextran sodium sulfate-induced colitis |
topic | Basic Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889820/ https://www.ncbi.nlm.nih.gov/pubmed/29632421 http://dx.doi.org/10.3748/wjg.v24.i13.1398 |
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