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.
abstract: 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.
authors.affiliation: Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, Illinois, United States of America; Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ueno
authors.affiliation: Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, Illinois, United States of America; Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Takumu
authors.initials: T
authors.lastname: Hasebe
authors.affiliation: Tsumura Research Laboratories, Tsumura and Co., Ami, Ibaraki, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kaneko
authors.affiliation: Tsumura Research Laboratories, Tsumura and Co., Ami, Ibaraki, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Fujiya
authors.affiliation: Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kohgo
authors.affiliation: Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Hokkaido, Japan; Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kono
authors.affiliation: Tang Center for Herbal Medicine Research, Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.affiliation: Tang Center for Herbal Medicine Research, Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
authors.affiliation: Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Marc
authors.initials: M
authors.lastname: Bissonnette
authors.affiliation: Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Chang
authors.affiliation: Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Musch
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D017252:CD3 Complex / Q000276:immunology; D045744:Cell Line, Tumor; D004751:Enteritis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D020939:Zingiber officinale / Q000737:chemistry*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007583:Jejunum / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D005894:Panax; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D032106:Zanthoxylum; D030521:Zingiberaceae
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C121414:dai-kenchu-to; D051057:Proto-Oncogene Proteins c-akt