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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2017-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00558/full |
| _version_ | 1818962279028228096 |
|---|---|
| author | Zecai Zhang Peng Shen Xiaojie Lu Yanxin Li Jiuxi Liu Bo Liu Yunhe Fu Yongguo Cao Naisheng Zhang |
| author_facet | Zecai Zhang Peng Shen Xiaojie Lu Yanxin Li Jiuxi Liu Bo Liu Yunhe Fu Yongguo Cao Naisheng Zhang |
| author_sort | Zecai Zhang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T12:26:48Z |
| format | Article |
| id | doaj.art-4a7ece7bedb347a0bc76c3cca4bfd93e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T12:26:48Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4a7ece7bedb347a0bc76c3cca4bfd93e2022-12-21T19:40:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-05-01810.3389/fimmu.2017.00558259311In Vivo and In Vitro Study on the Efficacy of Terpinen-4-ol in Dextran Sulfate Sodium-Induced Mice Experimental ColitisZecai Zhang0Peng Shen1Xiaojie Lu2Yanxin Li3Jiuxi Liu4Bo Liu5Yunhe Fu6Yongguo Cao7Naisheng Zhang8College of Veterinary Medicine, Jilin University, Changchun, ChinaCollege of Veterinary Medicine, Jilin University, Changchun, ChinaCollege of Veterinary Medicine, Jilin University, Changchun, ChinaCollege of Veterinary Medicine, Jilin University, Changchun, ChinaCollege of Veterinary Medicine, Jilin University, Changchun, ChinaCollege of Veterinary Medicine, Jilin University, Changchun, ChinaCollege of Veterinary Medicine, Jilin University, Changchun, ChinaCollege of Veterinary Medicine, Jilin University, Changchun, ChinaCollege of Veterinary Medicine, Jilin University, Changchun, ChinaThe 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.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00558/fullterpinen-4-olcolitisNLRP3 inflammasomeinterleukin-1βintestinal microbiotaintestinal barrier |
| spellingShingle | Zecai Zhang Peng Shen Xiaojie Lu Yanxin Li Jiuxi Liu Bo Liu Yunhe Fu Yongguo Cao Naisheng Zhang In Vivo and In Vitro Study on the Efficacy of Terpinen-4-ol in Dextran Sulfate Sodium-Induced Mice Experimental Colitis Frontiers in Immunology terpinen-4-ol colitis NLRP3 inflammasome interleukin-1β intestinal microbiota intestinal barrier |
| 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 | terpinen-4-ol colitis NLRP3 inflammasome interleukin-1β intestinal microbiota intestinal barrier |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00558/full |
| work_keys_str_mv | AT zecaizhang invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT pengshen invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT xiaojielu invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT yanxinli invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT jiuxiliu invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT boliu invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT yunhefu invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT yongguocao invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis AT naishengzhang invivoandinvitrostudyontheefficacyofterpinen4olindextransulfatesodiuminducedmiceexperimentalcolitis |