Atractylodin Attenuates Dextran Sulfate Sodium-Induced Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting Inflammatory Response Through the MAPK Pathway
In this study, we investigated the therapeutic effects and mechanism of atractylodin (ATL) on dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. We found that atractylodin could significantly reverse the effects of DSS-induced ulcerative colitis, such as weight loss, disease activity i...
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.665376/full |
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| author | Linghang Qu Xiong Lin Chunlian Liu Chang Ke Zhongshi Zhou Zhongshi Zhou Kang Xu Kang Xu Guosheng Cao Guosheng Cao Yanju Liu Yanju Liu |
| author_facet | Linghang Qu Xiong Lin Chunlian Liu Chang Ke Zhongshi Zhou Zhongshi Zhou Kang Xu Kang Xu Guosheng Cao Guosheng Cao Yanju Liu Yanju Liu |
| author_sort | Linghang Qu |
| collection | DOAJ |
| description | In this study, we investigated the therapeutic effects and mechanism of atractylodin (ATL) on dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. We found that atractylodin could significantly reverse the effects of DSS-induced ulcerative colitis, such as weight loss, disease activity index score; shorten the colon length, and reverse the pathological changes in the colon of mice. Atractylodin could inhibit the activation of colonic macrophages by inhibiting the MAPK pathway and alleviate intestinal inflammation in the mouse model of ulcerative colitis. Moreover, it could protect the intestinal barrier by inhibiting the decrease of the tight junction proteins, ZO-1, occludin, and MUC2. Additionally, atractylodin could decrease the abundance of harmful bacteria and increase that of beneficial bacteria in the intestinal tract of mice, effectively improving the intestinal microecology. In an LPS-induced macrophage model, atractylodin could inhibit the MAPK pathway and expression of the inflammatory factors of macrophages. Atractylodin could also inhibit the production of lactate, which is the end product of glycolysis; inhibit the activity of GAPDH, which is an important rate-limiting enzyme in glycolysis; inhibit the malonylation of GAPDH, and, thus, inhibit the translation of TNF-α. Therefore, ours is the first study to highlight the potential of atractylodin in the treatment of ulcerative colitis and reveal its possible mechanism. |
| first_indexed | 2024-12-16T17:40:50Z |
| format | Article |
| id | doaj.art-dd3d81023adc40dd9233099cc76984d6 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-16T17:40:50Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-dd3d81023adc40dd9233099cc76984d62022-12-21T22:22:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-07-011210.3389/fphar.2021.665376665376Atractylodin Attenuates Dextran Sulfate Sodium-Induced Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting Inflammatory Response Through the MAPK PathwayLinghang Qu0Xiong Lin1Chunlian Liu2Chang Ke3Zhongshi Zhou4Zhongshi Zhou5Kang Xu6Kang Xu7Guosheng Cao8Guosheng Cao9Yanju Liu10Yanju Liu11College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaCollege of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaCollege of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaCollege of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaCollege of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaCenter for Hubei TCM Processing Technology Engineering, Wuhan, ChinaCollege of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaCenter for Hubei TCM Processing Technology Engineering, Wuhan, ChinaCollege of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaCenter for Hubei TCM Processing Technology Engineering, Wuhan, ChinaCollege of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaCenter for Hubei TCM Processing Technology Engineering, Wuhan, ChinaIn this study, we investigated the therapeutic effects and mechanism of atractylodin (ATL) on dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. We found that atractylodin could significantly reverse the effects of DSS-induced ulcerative colitis, such as weight loss, disease activity index score; shorten the colon length, and reverse the pathological changes in the colon of mice. Atractylodin could inhibit the activation of colonic macrophages by inhibiting the MAPK pathway and alleviate intestinal inflammation in the mouse model of ulcerative colitis. Moreover, it could protect the intestinal barrier by inhibiting the decrease of the tight junction proteins, ZO-1, occludin, and MUC2. Additionally, atractylodin could decrease the abundance of harmful bacteria and increase that of beneficial bacteria in the intestinal tract of mice, effectively improving the intestinal microecology. In an LPS-induced macrophage model, atractylodin could inhibit the MAPK pathway and expression of the inflammatory factors of macrophages. Atractylodin could also inhibit the production of lactate, which is the end product of glycolysis; inhibit the activity of GAPDH, which is an important rate-limiting enzyme in glycolysis; inhibit the malonylation of GAPDH, and, thus, inhibit the translation of TNF-α. Therefore, ours is the first study to highlight the potential of atractylodin in the treatment of ulcerative colitis and reveal its possible mechanism.https://www.frontiersin.org/articles/10.3389/fphar.2021.665376/fullulcerative colitismalonylationatractylodinMAPK pathwaytight junctions |
| spellingShingle | Linghang Qu Xiong Lin Chunlian Liu Chang Ke Zhongshi Zhou Zhongshi Zhou Kang Xu Kang Xu Guosheng Cao Guosheng Cao Yanju Liu Yanju Liu Atractylodin Attenuates Dextran Sulfate Sodium-Induced Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting Inflammatory Response Through the MAPK Pathway Frontiers in Pharmacology ulcerative colitis malonylation atractylodin MAPK pathway tight junctions |
| title | Atractylodin Attenuates Dextran Sulfate Sodium-Induced Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting Inflammatory Response Through the MAPK Pathway |
| title_full | Atractylodin Attenuates Dextran Sulfate Sodium-Induced Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting Inflammatory Response Through the MAPK Pathway |
| title_fullStr | Atractylodin Attenuates Dextran Sulfate Sodium-Induced Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting Inflammatory Response Through the MAPK Pathway |
| title_full_unstemmed | Atractylodin Attenuates Dextran Sulfate Sodium-Induced Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting Inflammatory Response Through the MAPK Pathway |
| title_short | Atractylodin Attenuates Dextran Sulfate Sodium-Induced Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting Inflammatory Response Through the MAPK Pathway |
| title_sort | atractylodin attenuates dextran sulfate sodium induced colitis by alleviating gut microbiota dysbiosis and inhibiting inflammatory response through the mapk pathway |
| topic | ulcerative colitis malonylation atractylodin MAPK pathway tight junctions |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.665376/full |
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