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Trichodimerol inhibits inflammation through suppression of the nuclear transcription factor-kappaB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway
Excessive inflammation causes chronic diseases and tissue damage. Although there has been drug treatment, its side effects are relatively large. Searching for effective anti-inflammatory drugs from natural products has become the focus of attention. First isolated from Trichoderma longibraciatum, tr...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9445571/ https://www.ncbi.nlm.nih.gov/pubmed/36081795 http://dx.doi.org/10.3389/fmicb.2022.999996 |
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author | Huo, Xue-Yan Lei, Li-Rong Guo, Wen-Xiu Hu, Yun-Jie Kuang, Qi-Xuan Liu, Meng-Dan Peng, Wan Dai, Yi-Fei Wang, Dong Gu, Yu-Cheng Guo, Da-Le Deng, Yun |
author_facet | Huo, Xue-Yan Lei, Li-Rong Guo, Wen-Xiu Hu, Yun-Jie Kuang, Qi-Xuan Liu, Meng-Dan Peng, Wan Dai, Yi-Fei Wang, Dong Gu, Yu-Cheng Guo, Da-Le Deng, Yun |
author_sort | Huo, Xue-Yan |
collection | PubMed |
description | Excessive inflammation causes chronic diseases and tissue damage. Although there has been drug treatment, its side effects are relatively large. Searching for effective anti-inflammatory drugs from natural products has become the focus of attention. First isolated from Trichoderma longibraciatum, trichodimerol is a natural product with TNF inhibition. In this study, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as a model to investigate the anti-inflammatory activity of trichodimerol. The results of nitric oxide (NO) detection, enzyme-linked immunosorbent assay (ELISA), and reactive oxygen species (ROS) showed that trichodimerol could reduce the production of NO, ROS, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Western blotting results showed that trichodimerol could inhibit the production of inflammatory mediators such as cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the protein expression of nuclear transcription factor-kappaB (NF-κB), p-IKK, p-IκB, Toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteinyl aspartate specific proteinase (Caspase)-1, and ASC, which indicated that trichodimerol may inhibit inflammation through the NF-κB and NLRP3 pathways. At the same time, molecular docking showed that trichodimerol can directly combine with the TLR4-MD2 complex. Hence, trichodimerol inhibits inflammation by obstructing the interaction between LPS and the TLR4-MD2 heterodimer and suppressing the downstream NF-κB and NLRP3 pathways. |
format | Online Article Text |
id | pubmed-9445571 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94455712022-09-07 Trichodimerol inhibits inflammation through suppression of the nuclear transcription factor-kappaB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway Huo, Xue-Yan Lei, Li-Rong Guo, Wen-Xiu Hu, Yun-Jie Kuang, Qi-Xuan Liu, Meng-Dan Peng, Wan Dai, Yi-Fei Wang, Dong Gu, Yu-Cheng Guo, Da-Le Deng, Yun Front Microbiol Microbiology Excessive inflammation causes chronic diseases and tissue damage. Although there has been drug treatment, its side effects are relatively large. Searching for effective anti-inflammatory drugs from natural products has become the focus of attention. First isolated from Trichoderma longibraciatum, trichodimerol is a natural product with TNF inhibition. In this study, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as a model to investigate the anti-inflammatory activity of trichodimerol. The results of nitric oxide (NO) detection, enzyme-linked immunosorbent assay (ELISA), and reactive oxygen species (ROS) showed that trichodimerol could reduce the production of NO, ROS, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Western blotting results showed that trichodimerol could inhibit the production of inflammatory mediators such as cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the protein expression of nuclear transcription factor-kappaB (NF-κB), p-IKK, p-IκB, Toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteinyl aspartate specific proteinase (Caspase)-1, and ASC, which indicated that trichodimerol may inhibit inflammation through the NF-κB and NLRP3 pathways. At the same time, molecular docking showed that trichodimerol can directly combine with the TLR4-MD2 complex. Hence, trichodimerol inhibits inflammation by obstructing the interaction between LPS and the TLR4-MD2 heterodimer and suppressing the downstream NF-κB and NLRP3 pathways. Frontiers Media S.A. 2022-08-23 /pmc/articles/PMC9445571/ /pubmed/36081795 http://dx.doi.org/10.3389/fmicb.2022.999996 Text en Copyright © 2022 Huo, Lei, Guo, Hu, Kuang, Liu, Peng, Dai, Wang, Gu, Guo and Deng. 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 | Microbiology Huo, Xue-Yan Lei, Li-Rong Guo, Wen-Xiu Hu, Yun-Jie Kuang, Qi-Xuan Liu, Meng-Dan Peng, Wan Dai, Yi-Fei Wang, Dong Gu, Yu-Cheng Guo, Da-Le Deng, Yun Trichodimerol inhibits inflammation through suppression of the nuclear transcription factor-kappaB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway |
title | Trichodimerol inhibits inflammation through suppression of the nuclear transcription factor-kappaB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway |
title_full | Trichodimerol inhibits inflammation through suppression of the nuclear transcription factor-kappaB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway |
title_fullStr | Trichodimerol inhibits inflammation through suppression of the nuclear transcription factor-kappaB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway |
title_full_unstemmed | Trichodimerol inhibits inflammation through suppression of the nuclear transcription factor-kappaB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway |
title_short | Trichodimerol inhibits inflammation through suppression of the nuclear transcription factor-kappaB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway |
title_sort | trichodimerol inhibits inflammation through suppression of the nuclear transcription factor-kappab/nod-like receptor thermal protein domain associated protein 3 signaling pathway |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9445571/ https://www.ncbi.nlm.nih.gov/pubmed/36081795 http://dx.doi.org/10.3389/fmicb.2022.999996 |
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