Possible anti-inflammatory role of Zingiberis processum rhizoma, one component of the Kampo formula daikenchuto, against neutrophil infiltration through muscarinic acetylcholine receptor activation

Abstract Zingiberis processum rhizoma (ZPR) is a major active component of daikenchuto (DKT), which induces anti-inflammatoryaction by inhibiting macrophage infiltration. However, it is unclear whether ZPR is related to DKT-induced anti-inflammatoryaction via a reduction of neutrophil infiltration against postoperative ileus(POI). In this study, we orally administered individual herbal components of DKT to mice four times before and after intestinal manipulation (IM). The anti-inflammatoryaction of each crude drug was evaluated by histochemical analysis of relevant molecules. The results showed that treatment with all herbal components of DKT significantly inhibits neutrophil infiltration. This inhibition of neutrophil infiltration by ZPR was significantly reduced in 5-hydroxytryptamine receptor 4 (5-HT 4 R) knockout (KO) mice but not in alpha-7 nicotinic acetylcholine receptor(α7nAChR) KO mice. Also, transient receptor potential ankyrin1 (TRPA1) and muscarinic acetylcholine receptor(mAChR) antagonists partly and significantly inhibited the amelioration of neutrophil infiltration by ZPR. Therefore, DKT-induced anti-inflammatoryaction, mediated by inhibition of neutrophil infiltration in POI, depends, in part, on the effects of ZPR. ZPR activates TRPA1 channels, possibly in enterochromaffin (EC) cells, to release 5-HT. This 5-HT stimulates 5-HT 4 R in the myenteric plexusneurons to release acetylcholine, which, in turn, activates mAChR to inhibit inflammation in POI.