PMID- 24857966 OWN - NLM STAT- MEDLINE DCOM- 20150227 LR - 20240109 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 5 DP - 2014 TI - TU-100 (Daikenchuto) and ginger ameliorate anti-CD3 antibody induced T cell-mediated murine enteritis: microbe-independent effects involving Akt and NF-kappaB suppression. PG - e97456 LID - 10.1371/journal.pone.0097456 [doi] LID - e97456 AB - 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 TNFalpha, 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-kappaB 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 TNFalpha that activates epithelial cell NF-kappaB. TU-100 and ginger blocked anti-CD3 antibody activation of Akt in Jurkat cells, decreasing their TNFalpha production. Additionally, TU-100 and ginger alone blocked direct TNFalpha 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. FAU - Ueno, Nobuhiro AU - Ueno N AD - 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. FAU - Hasebe, Takumu AU - Hasebe T AD - 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. FAU - Kaneko, Atsushi AU - Kaneko A AD - Tsumura Research Laboratories, Tsumura and Co., Ami, Ibaraki, Japan. FAU - Yamamoto, Masahiro AU - Yamamoto M AD - Tsumura Research Laboratories, Tsumura and Co., Ami, Ibaraki, Japan. FAU - Fujiya, Mikihiro AU - Fujiya M AD - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. FAU - Kohgo, Yutaka AU - Kohgo Y AD - Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. FAU - Kono, Toru AU - Kono T AD - 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. FAU - Wang, Chong-Zhi AU - Wang CZ AD - Tang Center for Herbal Medicine Research, Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois, United States of America. FAU - Yuan, Chun-Su AU - Yuan CS AD - Tang Center for Herbal Medicine Research, Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois, United States of America. FAU - Bissonnette, Marc AU - Bissonnette M AD - Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, Illinois, United States of America. FAU - Chang, Eugene B AU - Chang EB AD - Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, Illinois, United States of America. FAU - Musch, Mark W AU - Musch MW AD - Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, Illinois, United States of America. LA - eng GR - UL1 TR000430/TR/NCATS NIH HHS/United States GR - P30 DK042086/DK/NIDDK NIH HHS/United States GR - R01 CA164124/CA/NCI NIH HHS/United States GR - K01 AT005362/AT/NCCIH NIH HHS/United States GR - R01 CA036745/CA/NCI NIH HHS/United States GR - P01 AT004418/AT/NCCIH NIH HHS/United States GR - R37 DK047722/DK/NIDDK NIH HHS/United States GR - DK097268/DK/NIDDK NIH HHS/United States GR - R01 DK047722/DK/NIDDK NIH HHS/United States GR - AT004418/AT/NCCIH NIH HHS/United States GR - CA036745/CA/NCI NIH HHS/United States GR - DK47722/DK/NIDDK NIH HHS/United States GR - AT005362/AT/NCCIH NIH HHS/United States GR - R01 DK097268/DK/NIDDK NIH HHS/United States GR - P30 DK42086/DK/NIDDK NIH HHS/United States GR - R37 CA036745/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140523 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antibodies, Monoclonal) RN - 0 (CD3 Complex) RN - 0 (NF-kappa B) RN - 0 (Plant Extracts) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (dai-kenchu-to) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Antibodies, Monoclonal/*adverse effects/immunology MH - Apoptosis/drug effects MH - CD3 Complex/immunology MH - Cell Line, Tumor MH - Enteritis/chemically induced/*drug therapy/immunology/metabolism MH - Enzyme Activation/drug effects MH - Zingiber officinale/*chemistry MH - Humans MH - Intestinal Mucosa/drug effects/pathology MH - Jejunum/drug effects/immunology/pathology MH - Mice MH - NF-kappa B/*metabolism MH - Panax MH - Plant Extracts/*pharmacology/therapeutic use MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Specific Pathogen-Free Organisms MH - T-Lymphocytes/*drug effects/immunology MH - Tumor Necrosis Factor-alpha/metabolism MH - Zanthoxylum MH - Zingiberaceae PMC - PMC4032249 COIS- Competing Interests: Drs. Kaneko and Yamamoto are employees of Tsumura & Co., one of the funders of this study. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all of the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. EDAT- 2014/05/27 06:00 MHDA- 2015/02/28 06:00 PMCR- 2014/05/23 CRDT- 2014/05/27 06:00 PHST- 2014/03/12 00:00 [received] PHST- 2014/04/14 00:00 [accepted] PHST- 2014/05/27 06:00 [entrez] PHST- 2014/05/27 06:00 [pubmed] PHST- 2015/02/28 06:00 [medline] PHST- 2014/05/23 00:00 [pmc-release] AID - PONE-D-14-10864 [pii] AID - 10.1371/journal.pone.0097456 [doi] PST - epublish SO - PLoS One. 2014 May 23;9(5):e97456. doi: 10.1371/journal.pone.0097456. eCollection 2014.