Department of Clinical Research, Oriental Medicine Research Center, Kitasato University, Tokyo, Japan.
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
Neurogastroenterol Motil. 2017 Dec;29(12). doi: 10.1111/nmo.13139. Epub 2017 Jun 28.
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.
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.
Treatment with Zingiberis Siccatum Rhizoma (ZSR) but not the other components inhibited the infiltration of cluster of differentiation 68 (CD68)-positive macrophages as effectively as DKT treatment. Selective α7nAChR antagonists, such as methyllycaconitine citrate, or transient receptor potential ankyrin 1 (TRPA1) 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 α7nAChR and 5-hydroxytryptamine 4 receptor (5-HT 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 TRPA1 channels possibly in enterochromaffin (EC) cells to release 5-HT, which stimulates 5-HT R in the myenteric plexus neurons to release ACh, which in turn activates α7nAChR on macrophages to inhibit inflammation in POI.
我们之前报道过大柴胡汤（DKT），一种用于治疗术后肠梗阻（POI）的胃肠道促动力日本草药（汉方）药物，具有独特的强效抗炎活性。这种作用可能部分是通过激活α7 烟碱型乙酰胆碱受体（nAChR）介导的。在这项研究中，我们确定了 DKT 中诱导抗炎作用的特定草药。
在对回肠远端进行肠道操作（IM）之前和之后，将 DKT 的草药成分分别口服给予每只小鼠四次。随后使用相关分子的免疫组织化学分析评估每种粗提物的抗炎活性。
与 DKT 处理一样，姜黄（ZSR）处理可有效抑制 CD68 阳性巨噬细胞的浸润，但其他成分则无效。选择性 α7nAChR 拮抗剂，如甲基-lycaconitine 柠檬酸，或瞬时受体电位锚蛋白 1（TRPA1）拮抗剂，如 HC-030031，可显著抑制 ZSR 改善巨噬细胞浸润的作用。在 α7nAChR 和 5-羟色胺 4 受体（5-HT R）敲除小鼠中，ZSR 对巨噬细胞浸润的抑制作用被消除。
大柴胡汤诱导的抗炎活性是通过抑制 POI 中的巨噬细胞浸润介导的，这依赖于 ZSR 的作用。姜黄通过激活肠嗜铬细胞（EC）细胞中的 TRPA1 通道可能释放 5-HT，刺激肌间神经丛神经元中的 5-HT R 释放 ACh，从而激活巨噬细胞上的 α7nAChR 抑制 POI 中的炎症。
