Daikenchuto ameliorates muscle hypercontractility in a murine T-cell-mediated persistent gut motor dysfunction model.
OBJECTIVE
Low-grade inflammation and immunological alterations are evident in functional gastrointestinal disorders such as irritable bowel syndrome (IBS). We evaluated the effects of daikenchuto (DKT), a pharmaceutical grade Japanese herbal medicine, on the hypercontractility of intestinal smooth muscle persisting after acute inflammation induced by a T-cell-activating anti-CD3 antibody (αCD3).


METHODS
BALB/c mice were injected with αCD3 (12.5 μg, i.p.), and DKT (2.7 g/kg) was administered orally once daily for 1 week. The contraction of isolated small intestinal muscle strips and muscle cells was examined on day 7 after αCD3 injection. The gene and protein expressions in the small intestines were evaluated by real-time PCR and multiplex immunoassays, respectively, on days 1, 3 and 7 after αCD3 injection.


RESULTS
αCD3 injection resulted in significant increases in carbachol-evoked contractility in the muscle strips and isolated smooth muscle cells on day 7. DKT ameliorated the αCD3-induced muscle hypercontractility on day 7 in both the muscle strips and smooth muscle cells. αCD3 injection rapidly up- and downregulated the mRNA and protein expressions of pro- and anti-inflammatory cytokines, respectively. Although the influence of DKT on the mRNA expressions was moderate, the protein expressions of IL-13 and IL-17 were significantly decreased.


CONCLUSIONS
We observed changes in the intestinal muscle contractility in muscle strips and muscle cells following resolution of inflammation in a T-cell-mediated model of enteropathy. The observed modulation of cytokine expression and function by DKT may lead to the development of new pharmacotherapeutic strategies aimed at a wide variety of gut motor dysfunction disorders.
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. akiho@intmed3.med.kyushu-u.ac.jp
Hirotada
H
Akiho
Kazuhiko
K
Nakamura
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D043183:Irritable Bowel Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D005894:Panax; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D032106:Zanthoxylum; D030521:Zingiberaceae
D017252:CD3 Complex; D016207:Cytokines; D010936:Plant Extracts; D012333:RNA, Messenger; C121414:dai-kenchu-to