Daikenchuto, a Japanese herbal medicine, ameliorates experimental colitis in a murine model by inducing secretory leukocyte protease inhibitor and modulating the gut microbiota

作者：Sotaro Ozaka, Akira Sonoda, Yoko Kudo, Kanako Ito, Naganori Kamiyama, Nozomi Sachi, Thanyakorn Chalalai, Yomei Kagoshima, Yasuhiro Soga, Supanuch Ekronarongchai, Shimpei Ariki, Kazuhiro Mizukami, Shiori Ishizawa, Mitsue Nishiyama, Kazunari Murakami, Kiyoshi Takeda, Takashi Kobayashi · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2024.1457562 · 被引用次数：10 · 研究领域：Barrier Structure and Function Studies、Inflammatory Bowel Disease、Gastrointestinal motility and disorders

Background: Inflammatory bowel disease (IBD) is a refractory inflammatory disorder of the intestine, which is probably triggered by dysfunction of the intestinal epithelial barrier. Secretory leukocyte protease inhibitor (SLPI) secreted by colon epithelial cells protects against intestinal inflammation by exerting anti-protease and anti-microbial activities. Daikenchuto (DKT) is one of the most commonly prescribed Japanese traditional herbal medicines for various digestive diseases. Although several animal studies have revealed that DKT exerts anti-inflammatory effects, its detailed molecular mechanism is unclear. This study aimed to clarify the anti-inflammatory mechanism of DKT using a murine colitis model, and to evaluate its potential as a therapeutic agent for IBD. Methods: Experimental colitis was induced in wild-type (WT) mice and SLPI-deficient (KO) mice by dextran sulfate sodium (DSS) after oral administration of DKT. The resultant clinical symptoms, histological changes, and pro-inflammatory cytokine levels in the colon were assessed. Expression of SLPI in the colon was detected by Western blotting and immunohistochemistry. Composition of the gut microbiota was analyzed by 16S rRNA metagenome sequencing and intestinal metabolites were measured by gas chromatography-mass spectrometry analysis. Intestinal epithelial barrier function was assessed by oral administration of FITC-dextran and immunostaining of tight junction proteins (TJPs). Results: , enhanced the levels ...