A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells.
A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells.
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DOI：
10.3389/fimmu.2022.903459
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发表时间：
2022
影响因子：
7.3
通讯作者：
Satoh-Takayama, Naoko
中科院分区：
文献类型：
--
作者：
Shi, Zhengzheng;Takeuchi, Tadashi;Nakanishi, Yumiko;Kato, Tamotsu;Beck, Katharina;Nagata, Ritsu;Kageyama, Tomoko;Ito, Ayumi;Ohno, Hiroshi;Satoh-Takayama, Naoko
关键词：
大kenchuto （DKT）是日本最广泛使用的用于各种胃肠疾病的草药配方之一。它由花椒（日本辣椒）、姜（加工姜）、人参和麦芽糖粉组成。然而，由于有限的分子证据和很大程度上未知的治疗效果，在临床环境中使用DKT仍然存在争议。本实验研究了DKT在右旋糖酐硫酸钠（DSS）诱导的小鼠结肠炎模型中的抗炎作用。我们观察到，DKT显著减轻了实验性结肠炎的严重程度，同时维持了共生微生物群的成员，如乳酸杆菌科，并增加了结肠中丙酸盐（一种免疫调节微生物代谢物）的水平。DKT还通过上调focusyltransferase基因Fut2和抗菌肽基因Reg3g来保护结肠上皮的完整性。更显著的是，DKT在dss诱导的结肠炎中恢复了减少的结肠3组先天淋巴样细胞（ILC3s），主要是rorγ -大腿-ILC3s。我们进一步证明，ilc3缺陷小鼠在实验性结肠炎期间死亡率增加，表明ilc3对结肠炎症起保护作用。这些发现表明DKT具有抗炎活性，部分通过ILC3功能维持结肠微环境。我们的研究还提供了对草药作用的分子基础的见解，促进了对草药配方的更深入的机制研究，并有助于未来的药物开发。
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.
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影响因子：
12.2
作者：
Jang, You Jin;Kim, Woon-Ki;Ko, Gwangpyo
通讯作者：
Ko, Gwangpyo
影响因子：
6.3
作者：
Endo, Mari;Hori, Masatoshi;Ozaki, Hiroshi;Oikawa, Tetsuro;Hanawa, Toshihiko
通讯作者：
Hanawa, Toshihiko
影响因子：
2.5
作者：
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通讯作者：
Sahara, Rikisaburo
影响因子：
35.7
作者：
Alatab, Sudabeh;Sepanlou, Sadaf G.;Naghavi, Mohsen
通讯作者：
Naghavi, Mohsen
影响因子：
4.1
作者：
Kim, Da Hye;Kim, Soochan;Cheon, Jae Hee
通讯作者：
Cheon, Jae Hee