How a Japanese Herbal Medicine Protects the Gut Against Inflammatory Bowel Disease

Summary: DKT, a Japanese herbal remedy containing ginger, pepper, ginseng and maltose, reduced symptoms of colitis in mice, according to a new study.


Zhengzheng Shi and colleagues at the RIKEN Center for Integrative Medical Sciences (IMS) in Japan report the effects of a common herbal remedy on colitis, one of two conditions that include inflammatory bowel disease (IBD). ).

Posted in Frontiers in immunologythe study shows that DKT – a standard formula containing ginger, pepper, ginseng and maltose – reduces the severity of colitis in laboratory mice by preventing the characteristic imbalance of intestinal microbes and by increasing the levels of immune cells in the colon that fight inflammation.

Colitis is a chronic inflammation of the colon, characterized by an imbalance of gut bacteria and an abnormal immune response. The prevalence has doubled in the past 20 years, and it is currently a global health problem, particularly in Europe and North America. Although there are many treatments, they are only partially effective.

This has led some researchers to take a closer look at traditional herbal medicines that originated in China and are now commonly used in Japan and other Asian countries.

Daikenchuto (DKT) is a formula containing specific amounts of ginger, pepper, ginseng and maltose, and is one of 148 herbal medicines called Kampo, which were developed in Japan and are often prescribed by doctors to treat various diseases.

Previous research has suggested that DKT may be useful for treating colitis, but evidence, particularly at the molecular level, is lacking. So Shi and the RIKEN IMS team of researchers led by Naoko Satoh-Takayama conducted a detailed examination of its effects in a mouse model of colitis.

Colitis has been induced in mice using dextran sodium sulfate, which is toxic to the cells that line the colon. When these mice received DKT, their body weights remained normal and they had lower clinical scores for colitis. Further analysis revealed significantly less damage to the cells lining the colon.

Having thus shown that DKT effectively contributed to protecting against colitis, the researchers proceeded to analyze the intestinal microbiome of mice and the levels of expression of anti-inflammatory immune cells.

Gut microbiomes contain many bacteria and fungi that aid digestion and help the immune system.

Colitis is a chronic inflammation of the colon, characterized by an imbalance of gut bacteria and an abnormal immune response. Image is in public domain

Colitis is associated with an imbalance of this gut microbiota, and analysis showed that a family of lactic acid bacteria was depleted in the colonic mice in this study. One of their metabolites, a short chain fatty acid called propionate, was also depleted.

Treatment of model mice with DKT restored much of these missing bacteria, especially those of the genus Lactobacillus, and propionate levels were normal.

Colitis is also associated with an abnormal immune response that causes the characteristic intestinal inflammation.

When the team looked at innate intestinal immune cells, they found that levels of a type called ILC3 were lower in untreated colic mice than in DKT-treated colic mice, and that mice engineered to lack d ‘ILC3 suffered more and could not benefit from DKT. treatment.

This means that ILC3s are essential for protection against colitis and that DKT works by interacting with them. Finally, qPCR analysis indicated that these important immune cells had receptors for propionate, called GPR43, on their surface.

“Daikenchuto is commonly prescribed to prevent and treat gastrointestinal illnesses, as well as to reduce bowel obstruction after colorectal cancer surgery,” says Satoh-Takayama.

“Here we have shown that it can also relieve gut diseases like colitis by rebalancing Lactobacillus levels in the gut microbiome. This likely helps reduce inflammatory immune responses by promoting the activity of type 3 innate lymphoid cells.”

About this IBD research news

Author: Press office
Contact: Press office – RIKEN
Image: Image is in public domain

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Original research: Free access.
“A Japanese Herbal Formula, Daikenchuto, Relieves Experimental Colitis by Reshaping Microbial Profiles and Improving Innate Group 3 Lymphoid Cells” by Zhengzheng Shi et al. Frontiers in immunology


A Japanese Herbal Formula, Daikenchuto, Relieves Experimental Colitis by Reshaping Microbial Profiles and Improving Group 3 Innate Lymphoid Cells

Daikenchuto (DKT) is one of the most widely used Japanese herbal formulas for various gastrointestinal disorders. That consists of Zanthoxylum Fructus (Japanese pepper), Zingiberis Siccatum Rhizome (processed ginger), Ginseng base, and maltose powder. However, the use of DKT in the clinical setting is still controversial due to limited molecular evidence and largely unknown therapeutic effects.

Here, we investigated the anti-inflammatory actions of DKT in the mouse model of dextran sodium sulfate (DSS)-induced colitis.

We observed that DKT remarkably attenuated the severity of experimental colitis while maintaining members of the symbiotic microbiota such as the Lactobacillaceae family and increasing levels of propionate, an immunomodulatory microbial metabolite, in the colon.

DKT also protected colonic epithelial integrity by up-regulating the fucosyltransferase gene fut2 and the antimicrobial peptide gene Reg3g. Most remarkably, DKT restored colon group 3 (ILC3) reduced innate lymphoid cells, primarily RORγthigh-ILC3s, in DSS-induced colitis. We further demonstrated that ILC3-deficient mice exhibited increased mortality during experimental colitis, suggesting that ILC3s play a protective role against colonic inflammation.

These results demonstrate that DKT possesses anti-inflammatory activity, in part Going through ILC3 function, to maintain the colonic microenvironment.

Our study also provides insights into the molecular basis of herbal medicine effects, promotes further mechanistic studies of herbal formulations, and contributes to future drug development.

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