Possible anti-inflammatory role of Zingiberis processum rhizoma, one component of the Kampo formula daikenchuto, against neutrophil infiltration through muscarinic acetylcholine receptor activation
Possible anti-inflammatory role of Zingiberis processum rhizoma, one component of the Kampo formula daikenchuto, against neutrophil infiltration through muscarinic acetylcholine receptor activation
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DOI：
10.1016/j.jphs.2018.08.001
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发表时间：
2018-08-01
影响因子：
3.5
通讯作者：
Hanawa, Toshihiko
中科院分区：
文献类型：
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作者：
Endo, Mari;Hori, Masatoshi;Hanawa, Toshihiko
Zingiberis processum rhizoma （ZPR）是daikenchuto （DKT）的主要活性成分，它通过抑制巨噬细胞的浸润而具有抗炎作用。然而，目前尚不清楚ZPR是否与dkt诱导的抗炎作用有关，通过减少中性粒细胞浸润来对抗术后肠梗阻（POI）。在本研究中，我们在肠道操作（IM）前后四次口服DKT的单个草药成分。通过相关分子的组织化学分析，评价各生药的抗炎作用。结果表明，DKT各成分处理均能显著抑制中性粒细胞的浸润。ZPR对中性粒细胞浸润的抑制作用在5-羟色胺受体4 （5-HT4R）敲除（KO）小鼠中显著降低，而在α -7烟碱乙酰胆碱受体（α 7nAChR） KO小鼠中则没有。瞬时受体电位锚蛋白1 （TRPA1）和毒蕈碱乙酰胆碱受体（mAChR）拮抗剂部分显著抑制ZPR对中性粒细胞浸润的改善作用。因此，dkt诱导的抗炎作用，通过抑制POI中性粒细胞浸润介导，部分取决于ZPR的作用。ZPR激活TRPA1通道，可能在肠染色质（EC）细胞中，释放5-HT。这种5-HT刺激肌肠丛神经元中的5-HT4R释放乙酰胆碱，从而激活mAChR抑制POI的炎症。(c) 2018年作者。由Elsevier B.V.代表日本药理学会制作和主办。
Zingiberis processum rhizoma (ZPR) is a major active component of daikenchuto (DKT), which induces anti-inflammatory action by inhibiting macrophage infiltration. However, it is unclear whether ZPR is related to DKT-induced anti-inflammatory action 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-inflammatory action 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-HT4R) knockout (KO) mice but not in alpha-7 nicotinic acetylcholine receptor (alpha 7nAChR) KO mice. Also, transient receptor potential ankyrin 1 (TRPA1) and muscarinic acetylcholine receptor (mAChR) antagonists partly and significantly inhibited the amelioration of neutrophil infiltration by ZPR. Therefore, DKT-induced anti-inflammatory action, 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-HT4R in the myenteric plexus neurons to release acetylcholine, which, in turn, activates mAChR to inhibit inflammation in POI. (c) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.