A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells
Daikenchuto (DKT) is one of the most widely used Japanese herbal formulae for various gastrointestinal disorders. It consists of Zanthoxylum Fructus (Japanese pepper), Zingiberis Siccatum Rhizoma (processed ginger), Ginseng radix, and maltose powder. However, the use of DKT in clinical settings is s...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.903459/full |
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| author | Zhengzheng Shi Zhengzheng Shi Tadashi Takeuchi Yumiko Nakanishi Yumiko Nakanishi Tamotsu Kato Tamotsu Kato Katharina Beck Ritsu Nagata Ritsu Nagata Tomoko Kageyama Tomoko Kageyama Ayumi Ito Ayumi Ito Hiroshi Ohno Hiroshi Ohno Hiroshi Ohno Naoko Satoh-Takayama Naoko Satoh-Takayama |
| author_facet | Zhengzheng Shi Zhengzheng Shi Tadashi Takeuchi Yumiko Nakanishi Yumiko Nakanishi Tamotsu Kato Tamotsu Kato Katharina Beck Ritsu Nagata Ritsu Nagata Tomoko Kageyama Tomoko Kageyama Ayumi Ito Ayumi Ito Hiroshi Ohno Hiroshi Ohno Hiroshi Ohno Naoko Satoh-Takayama Naoko Satoh-Takayama |
| author_sort | Zhengzheng Shi |
| collection | DOAJ |
| description | Daikenchuto (DKT) is one of the most widely used Japanese herbal formulae for various gastrointestinal disorders. It consists of Zanthoxylum Fructus (Japanese pepper), Zingiberis Siccatum Rhizoma (processed ginger), Ginseng radix, and maltose powder. However, the use of DKT in clinical settings is still controversial due to the limited molecular evidence and largely unknown therapeutic effects. Here, we investigated the anti-inflammatory actions of DKT in the dextran sodium sulfate (DSS)-induced colitis model in mice. We observed that DKT remarkably attenuated the severity of experimental colitis while maintaining the members of the symbiotic microbiota such as family Lactobacillaceae and increasing levels of propionate, an immunomodulatory microbial metabolite, in the colon. DKT also protected colonic epithelial integrity by upregulating the fucosyltransferase gene Fut2 and the antimicrobial peptide gene Reg3g. More remarkably, DKT restored the reduced colonic group 3 innate lymphoid cells (ILC3s), mainly RORγthigh-ILC3s, in DSS-induced colitis. We further demonstrated that ILC3-deficient mice showed increased mortality during experimental colitis, suggesting that ILC3s play a protective function on colonic inflammation. These findings demonstrate that DKT possesses anti-inflammatory activity, partly via ILC3 function, to maintain the colonic microenvironment. Our study also provides insights into the molecular basis of herbal medicine effects, promotes more profound mechanistic studies towards herbal formulae and contributes to future drug development. |
| first_indexed | 2024-04-12T11:09:10Z |
| format | Article |
| id | doaj.art-7a6bbb2a865240999b91fa184f2200dd |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T11:09:10Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7a6bbb2a865240999b91fa184f2200dd2022-12-22T03:35:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.903459903459A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid CellsZhengzheng Shi0Zhengzheng Shi1Tadashi Takeuchi2Yumiko Nakanishi3Yumiko Nakanishi4Tamotsu Kato5Tamotsu Kato6Katharina Beck7Ritsu Nagata8Ritsu Nagata9Tomoko Kageyama10Tomoko Kageyama11Ayumi Ito12Ayumi Ito13Hiroshi Ohno14Hiroshi Ohno15Hiroshi Ohno16Naoko Satoh-Takayama17Naoko Satoh-Takayama18Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanLaboratory for Immune Regulation, Graduate School of Medical and Pharmaceutical Sciences, Chiba University, Chiba, JapanLaboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanLaboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanImmunobiology Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, JapanLaboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanImmunobiology Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, JapanLaboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanLaboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanImmunobiology Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, JapanLaboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanImmunobiology Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, JapanLaboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanImmunobiology Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, JapanLaboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanLaboratory for Immune Regulation, Graduate School of Medical and Pharmaceutical Sciences, Chiba University, Chiba, JapanImmunobiology Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, JapanLaboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanImmunobiology Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, JapanDaikenchuto (DKT) is one of the most widely used Japanese herbal formulae for various gastrointestinal disorders. It consists of Zanthoxylum Fructus (Japanese pepper), Zingiberis Siccatum Rhizoma (processed ginger), Ginseng radix, and maltose powder. However, the use of DKT in clinical settings is still controversial due to the limited molecular evidence and largely unknown therapeutic effects. Here, we investigated the anti-inflammatory actions of DKT in the dextran sodium sulfate (DSS)-induced colitis model in mice. We observed that DKT remarkably attenuated the severity of experimental colitis while maintaining the members of the symbiotic microbiota such as family Lactobacillaceae and increasing levels of propionate, an immunomodulatory microbial metabolite, in the colon. DKT also protected colonic epithelial integrity by upregulating the fucosyltransferase gene Fut2 and the antimicrobial peptide gene Reg3g. More remarkably, DKT restored the reduced colonic group 3 innate lymphoid cells (ILC3s), mainly RORγthigh-ILC3s, in DSS-induced colitis. We further demonstrated that ILC3-deficient mice showed increased mortality during experimental colitis, suggesting that ILC3s play a protective function on colonic inflammation. These findings demonstrate that DKT possesses anti-inflammatory activity, partly via ILC3 function, to maintain the colonic microenvironment. Our study also provides insights into the molecular basis of herbal medicine effects, promotes more profound mechanistic studies towards herbal formulae and contributes to future drug development.https://www.frontiersin.org/articles/10.3389/fimmu.2022.903459/fullJapanese herbal medicine (Kampo medicine)Daikenchuto (DKT)biomolecular functions of herbal medicineexperimental colitisLactobacillaceaegut microbiota |
| spellingShingle | Zhengzheng Shi Zhengzheng Shi Tadashi Takeuchi Yumiko Nakanishi Yumiko Nakanishi Tamotsu Kato Tamotsu Kato Katharina Beck Ritsu Nagata Ritsu Nagata Tomoko Kageyama Tomoko Kageyama Ayumi Ito Ayumi Ito Hiroshi Ohno Hiroshi Ohno Hiroshi Ohno Naoko Satoh-Takayama Naoko Satoh-Takayama A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells Frontiers in Immunology Japanese herbal medicine (Kampo medicine) Daikenchuto (DKT) biomolecular functions of herbal medicine experimental colitis Lactobacillaceae gut microbiota |
| title | A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells |
| title_full | A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells |
| title_fullStr | A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells |
| title_full_unstemmed | A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells |
| title_short | A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells |
| title_sort | japanese herbal formula daikenchuto alleviates experimental colitis by reshaping microbial profiles and enhancing group 3 innate lymphoid cells |
| topic | Japanese herbal medicine (Kampo medicine) Daikenchuto (DKT) biomolecular functions of herbal medicine experimental colitis Lactobacillaceae gut microbiota |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.903459/full |
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