Cargando…
In Vivo and In Vitro Study on the Efficacy of Terpinen-4-ol in Dextran Sulfate Sodium-Induced Mice Experimental Colitis
The purpose of this study was to investigate the protective effects of Terpinen-4-ol (TER) on dextran sulfate sodium (DSS)-induced experimental colitis and clarify the possible mechanisms. In vivo, an acute colitis model was used to confirm the anti-inflammatory activity and the possible mechanisms...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427085/ https://www.ncbi.nlm.nih.gov/pubmed/28553294 http://dx.doi.org/10.3389/fimmu.2017.00558 |
_version_ | 1783235596310806528 |
---|---|
author | Zhang, Zecai Shen, Peng Lu, Xiaojie Li, Yanxin Liu, Jiuxi Liu, Bo Fu, Yunhe Cao, Yongguo Zhang, Naisheng |
author_facet | Zhang, Zecai Shen, Peng Lu, Xiaojie Li, Yanxin Liu, Jiuxi Liu, Bo Fu, Yunhe Cao, Yongguo Zhang, Naisheng |
author_sort | Zhang, Zecai |
collection | PubMed |
description | The purpose of this study was to investigate the protective effects of Terpinen-4-ol (TER) on dextran sulfate sodium (DSS)-induced experimental colitis and clarify the possible mechanisms. In vivo, an acute colitis model was used to confirm the anti-inflammatory activity and the possible mechanisms of TER in C57BL/6 and NLRP3(−/−) mice. In vitro, we performed further study, using RAW264.7 cells and Caco-2 cells, to confirm the molecular mechanisms of TER on inflammatory response. In C57BL/6 mice, TER alleviated DSS-induced disease activity index (DAI), colon length shortening, colonic pathological damage, and myeloperoxidase (MPO) activities. The production of pro-inflammatory mediators was significantly decreased by TER. Furthermore, TER inhibited NF-κB and NLRP3 inflammasome activation. Surprisingly, TER reduced the plasmatic lipopolysaccharide (LPS) concentration and re-balanced Escherichia coli (E. coli) and Lactobacillus levels. In addition, TER prevented the impairment of colon epithelium barrier by regulating the expression of zonula occludens-1 and occludin. In vitro, the results showed that TER significantly suppressed NLRP3 inflammasome activation in LPS-stimulated RAW264.7 cells, as indicated by decreased expression of NLRP3 and caspase-1, and lowered interleukin-1β secretion. In contrast, mice deficient for NLRP3 were less sensitive to DSS-induced acute colitis, and TER treatment exerted little protective effect on DSS-induced intestinal inflammation in NLRP3(−/−) mice. The protective effect of TER may be largely attributed to its inhibition of NLRP3 inflammasome activation in colon. Taken together, our findings showed that TER might be a potential agent for the treatment of ulcerative colitis. |
format | Online Article Text |
id | pubmed-5427085 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54270852017-05-26 In Vivo and In Vitro Study on the Efficacy of Terpinen-4-ol in Dextran Sulfate Sodium-Induced Mice Experimental Colitis Zhang, Zecai Shen, Peng Lu, Xiaojie Li, Yanxin Liu, Jiuxi Liu, Bo Fu, Yunhe Cao, Yongguo Zhang, Naisheng Front Immunol Immunology The purpose of this study was to investigate the protective effects of Terpinen-4-ol (TER) on dextran sulfate sodium (DSS)-induced experimental colitis and clarify the possible mechanisms. In vivo, an acute colitis model was used to confirm the anti-inflammatory activity and the possible mechanisms of TER in C57BL/6 and NLRP3(−/−) mice. In vitro, we performed further study, using RAW264.7 cells and Caco-2 cells, to confirm the molecular mechanisms of TER on inflammatory response. In C57BL/6 mice, TER alleviated DSS-induced disease activity index (DAI), colon length shortening, colonic pathological damage, and myeloperoxidase (MPO) activities. The production of pro-inflammatory mediators was significantly decreased by TER. Furthermore, TER inhibited NF-κB and NLRP3 inflammasome activation. Surprisingly, TER reduced the plasmatic lipopolysaccharide (LPS) concentration and re-balanced Escherichia coli (E. coli) and Lactobacillus levels. In addition, TER prevented the impairment of colon epithelium barrier by regulating the expression of zonula occludens-1 and occludin. In vitro, the results showed that TER significantly suppressed NLRP3 inflammasome activation in LPS-stimulated RAW264.7 cells, as indicated by decreased expression of NLRP3 and caspase-1, and lowered interleukin-1β secretion. In contrast, mice deficient for NLRP3 were less sensitive to DSS-induced acute colitis, and TER treatment exerted little protective effect on DSS-induced intestinal inflammation in NLRP3(−/−) mice. The protective effect of TER may be largely attributed to its inhibition of NLRP3 inflammasome activation in colon. Taken together, our findings showed that TER might be a potential agent for the treatment of ulcerative colitis. Frontiers Media S.A. 2017-05-12 /pmc/articles/PMC5427085/ /pubmed/28553294 http://dx.doi.org/10.3389/fimmu.2017.00558 Text en Copyright © 2017 Zhang, Shen, Lu, Li, Liu, Liu, Fu, Cao and Zhang. 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) or licensor 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 | Immunology Zhang, Zecai Shen, Peng Lu, Xiaojie Li, Yanxin Liu, Jiuxi Liu, Bo Fu, Yunhe Cao, Yongguo Zhang, Naisheng In Vivo and In Vitro Study on the Efficacy of Terpinen-4-ol in Dextran Sulfate Sodium-Induced Mice Experimental Colitis |
title | In Vivo and In Vitro Study on the Efficacy of Terpinen-4-ol in Dextran Sulfate Sodium-Induced Mice Experimental Colitis |
title_full | In Vivo and In Vitro Study on the Efficacy of Terpinen-4-ol in Dextran Sulfate Sodium-Induced Mice Experimental Colitis |
title_fullStr | In Vivo and In Vitro Study on the Efficacy of Terpinen-4-ol in Dextran Sulfate Sodium-Induced Mice Experimental Colitis |
title_full_unstemmed | In Vivo and In Vitro Study on the Efficacy of Terpinen-4-ol in Dextran Sulfate Sodium-Induced Mice Experimental Colitis |
title_short | In Vivo and In Vitro Study on the Efficacy of Terpinen-4-ol in Dextran Sulfate Sodium-Induced Mice Experimental Colitis |
title_sort | in vivo and in vitro study on the efficacy of terpinen-4-ol in dextran sulfate sodium-induced mice experimental colitis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427085/ https://www.ncbi.nlm.nih.gov/pubmed/28553294 http://dx.doi.org/10.3389/fimmu.2017.00558 |
work_keys_str_mv | AT zhangzecai invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT shenpeng invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT luxiaojie invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT liyanxin invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT liujiuxi invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT liubo invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT fuyunhe invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT caoyongguo invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT zhangnaisheng invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis |