The Japanese traditional medicine daikenchuto (TU-100) has anti-inflammatory activities, but the mechanisms remain incompletely understood. TU-100 includes ginger, ginseng, and Japanese pepper, each component possessing bioactive properties. The effects of TU-100 and individual components were investigated in a model of intestinal T lymphocyte activation using anti-CD3 antibody. To determine contribution of intestinal bacteria, specific pathogen free (SPF) and germ free (GF) mice were used. TU-100 or its components were delivered by diet or by gavage. Anti-CD3 antibody increased jejunal accumulation of fluid, increased TNFα, and induced intestinal epithelial apoptosis in both SPF and GF mice, which was blocked by either TU-100 or ginger, but not by ginseng or Japanese pepper. TU-100 and ginger also blocked anti-CD3-stimulated Akt and NF-κB activation. A co-culture system of colonic Caco2BBE and Jurkat-1 cells was used to examine T-lymphocyte/epithelial cells interactions. Jurkat-1 cells were stimulated with anti-CD3 to produce TNFα that activates epithelial cell NF-κB. TU-100 and ginger blocked anti-CD3 antibody activation of Akt in Jurkat cells, decreasing their TNFα production. Additionally, TU-100 and ginger alone blocked direct TNFα stimulation of Caco2BBE cells and decreased activation of caspase-3 and polyADP ribose. The present studies demonstrate a new anti-inflammatory action of TU-100 that is microbe-independent and due to its ginger component.
Details
Title
TU-100 (Daikenchuto) and Ginger Ameliorate Anti-CD3 Antibody Induced T Cell-Mediated Murine Enteritis: Microbe-Independent Effects Involving Akt and NF-κB Suppression
Author
Ueno, Nobuhiro : University of Chicago Hasebe, Takumu : University of Chicago Kaneko, Atsushi : Tsumura and Co. Yamamoto, Masahiro : Tsumura and Co. Fujiya, Mikihiro : Asahikawa Medical University Kohgo, Yutaka : Asahikawa Medical University Kono, Toru : Sapporo Higashi Tokushukai Hospital Wang, Chong-Zhi : University of Chicago Yuan, Chun-Su : University of Chicago Bissonnette, Marc : University of Chicago Chang, Eugene B. : University of Chicago Musch, Mark W. : University of Chicago
Data availability statement
The authors confirm that all data underlying the findings are fully available without restriction. All data are included within the manuscript and Supporting Information files.
Funding Information
National Institute of Diabetes and Digestive and Kidney Diseases, P30 DK42086 National Institute of Diabetes and Digestive and Kidney Diseases, DK47722 National Institute of Diabetes and Digestive and Kidney Diseases, DK097268 National Institute of Diabetes and Digestive and Kidney Diseases, NCCAM AT004418 National Institute of Diabetes and Digestive and Kidney Diseases, AT005362 National Institutes of Health, CA036745 Samuel Freedman Research Laboratories for Gastrointestinal Cancer Research University of Chicago Comprehensive Cancer Center