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Zingiberis Siccatum Rhizoma, the active component of the Kampo formula Daikenchuto, induces anti‐inflammatory actions through α7 nicotinic acetylcholine receptor activation
Author(s) -
Endo M.,
Hori M.,
Mihara T.,
Ozaki H.,
Oikawa T.,
Odaguchi H.,
Hanawa T.
Publication year - 2017
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13139
Subject(s) - kampo , pharmacology , inflammation , myenteric plexus , acetylcholine , infiltration (hvac) , methyllycaconitine , medicine , chemistry , receptor , nicotinic acetylcholine receptor , nicotinic agonist , pathology , immunohistochemistry , physics , alternative medicine , thermodynamics
Background We previously reported that Daikenchuto ( DKT ), a gastrointestinal prokinetic Japanese herbal (Kampo) medicine used for the treatment of postoperative ileus ( POI ), has characteristic potent anti‐inflammatory activity. This effect may be partly mediated by the activation of α7 nicotinic acetylcholine receptor ( nAChR ). In this study, we identified the specific herbs in DKT that induce anti‐inflammatory action. Methods The herbal components of DKT were individually administered orally to each mouse four times before and after intestinal manipulation ( IM ) was carried out on the distal ileum. The anti‐inflammatory activity of each crude drug was subsequently evaluated using immunohistochemical analyses of relevant molecules. Key Results Treatment with Zingiberis Siccatum Rhizoma ( ZSR ) but not the other components inhibited the infiltration of cluster of differentiation 68 ( CD 68)‐positive macrophages as effectively as DKT treatment. Selective α7n AC hR antagonists, such as methyllycaconitine citrate, or transient receptor potential ankyrin 1 ( TRPA 1) antagonists, such as HC ‐030031, significantly inhibited the amelioration of macrophage infiltration by ZSR . The inhibition of macrophage infiltration by ZSR was abolished in both α7n AC hR and 5‐hydroxytryptamine 4 receptor (5‐ HT 4 R) knockout mice. Conclusions & Inferences Daikenchuto‐induced anti‐inflammatory activity, which was mediated by inhibiting macrophage infiltration in POI , is dependent on the effects of ZSR . Zingiberis Siccatum Rhizoma activates TRPA 1 channels possibly in enterochromaffin ( EC ) cells to release 5‐ HT , which stimulates 5‐ HT 4 R in the myenteric plexus neurons to release AC h, which in turn activates α7n AC hR on macrophages to inhibit inflammation in POI .