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Daikenchuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus by anti-inflammatory action through nicotinic acetylcholine receptors.

Endo M, Hori M, Ozaki H, Oikawa T, Hanawa T - J. Gastroenterol. (2013)

Bottom Line: Several mechanisms for the amelioration of POI by DKT have been suggested; however, it has remained unclear whether DKT shows anti-inflammatory effects in POI.DKT significantly inhibited the infiltration of neutrophils and CD68-positive macrophages, and inhibited mRNA expressions of TNF-α and MCP-1.In conclusion, in addition to the gastrointestinal prokinetic action, DKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Research, Oriental Medicine Research Center, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan.

ABSTRACT

Background: Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal medicine, is prescribed for patients with postoperative ileus (POI) and adhesive bowel obstruction following abdominal surgery. Several mechanisms for the amelioration of POI by DKT have been suggested; however, it has remained unclear whether DKT shows anti-inflammatory effects in POI. In the present study, we investigated the effects of DKT in a mouse POI model and attempted to clarify the detailed mechanisms of action.

Method: Intestinal manipulation (IM) was applied to the distal ileum of mice. DKT was administered orally to the animals 4 times before and after IM. Gastrointestinal transit in vivo, leukocyte infiltration, cytokine mRNA expression and gastrointestinal motility were analyzed. We also investigated the effects of the α7nAChR antagonist methyllycaconitine citrate (MLA) on the DKT-mediated ameliorative action against POI, and we studied the effects of DKT on inflammatory activity in α7nAChR knockout mice.

Results: DKT treatment led to recovery of the delayed intestinal transit induced by IM. DKT significantly inhibited the infiltration of neutrophils and CD68-positive macrophages, and inhibited mRNA expressions of TNF-α and MCP-1. MLA significantly reduced the anti-inflammatory action of DKT, and the amelioration of macrophage infiltration by DKT was partially suppressed in α7nAChR knockout mice.

Conclusions: In conclusion, in addition to the gastrointestinal prokinetic action, DKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency. The DKT-induced anti-inflammatory activity may be partly mediated by activation of α7nAChR.

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Ameliorative effects of DKT on MPO-stained neutrophil infiltration in IM. a Indicates representative results for whole mount immunohistochemical staining of myenteric plexus region to detect MPO-positive neutrophils. b Shows quantification of neutrophil cells in n = 5/normal and IM + DKT (95 mg/kg) group, n = 7/IM + Vehicle and IM + DKT (19 mg/kg) group. Columns indicate mean ± SEM. ## and *: significantly different from normal and IM + Vehicle at P < 0.01 and P < 0.05, respectively
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Fig4: Ameliorative effects of DKT on MPO-stained neutrophil infiltration in IM. a Indicates representative results for whole mount immunohistochemical staining of myenteric plexus region to detect MPO-positive neutrophils. b Shows quantification of neutrophil cells in n = 5/normal and IM + DKT (95 mg/kg) group, n = 7/IM + Vehicle and IM + DKT (19 mg/kg) group. Columns indicate mean ± SEM. ## and *: significantly different from normal and IM + Vehicle at P < 0.01 and P < 0.05, respectively

Mentions: After DKT treatment, we immunohistochemically monitored changes in MPO-stained neutrophils, and CD68-positive resident and monocyte-derived macrophages, as shown in Figs. 4 and 5. In Fig. 4, MPO-stained neutrophil infiltration into the ileal muscle layer was increased in the IM + Vehicle group, as compared with that in the normal group. Neutrophil infiltration by IM was significantly ameliorated in the IM + DKT group. In Fig. 5, resident dendritic macrophages [30] stained by CD68 were present in the myenteric plexus region in normal intestine [26, 31]. At 24 h after IM, many infiltrating monocyte-derived macrophages and activated round [30] resident macrophages were observed, as reported previously [5]. The CD68-positive macrophage population increased 6-fold in the inflamed ileal muscle layer of the intestine of the IM + Vehicle group, as compared with the normal group. The increased CD68-positive macrophage population was significantly inhibited in the IM + DKT group, as compared with the IM group. However, DKT had no effects on MPO-stained neutrophils or CD68-positive macrophages in the control ileal muscle layer (MPO-positive cells: normal, 3.26 ± 1.46 cells/mm2, +DKT, 4.88 ± 1.49 cells/mm2; CD68-positive cells: normal, 646.16 ± 16.59 cells/mm2, +DKT, 626.63 ± 29.52 cells/mm2). Neutrophil infiltration and increased CD68-positive macrophage population by IM was significantly ameliorated in manufactured DKT, m-DKT treated group as it was in our hand-made DKT (MPO-positive cells: normal 1.05 ± 0.39 cells/mm2, IM 1653.66 ± 121.24 cells/mm2, IM + DKT 1047.47 ± 92.27 cells/mm2, P < 0.05, IM + m-DKT 603.0 ± 90.70 cells/mm2, P < 0.01, n = 4; CD68-positive cells: normal 186.71 ± 13.15 cells/mm2, IM 2095.99 ± 144.04 cells/mm2, IM + DKT 1484.53 ± 70.11 cells/mm2, P < 0.05, IM + m-DKT 1515.12 ± 71.51 cells/mm2, P < 0.05, n = 4).Fig. 4


Daikenchuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus by anti-inflammatory action through nicotinic acetylcholine receptors.

Endo M, Hori M, Ozaki H, Oikawa T, Hanawa T - J. Gastroenterol. (2013)

Ameliorative effects of DKT on MPO-stained neutrophil infiltration in IM. a Indicates representative results for whole mount immunohistochemical staining of myenteric plexus region to detect MPO-positive neutrophils. b Shows quantification of neutrophil cells in n = 5/normal and IM + DKT (95 mg/kg) group, n = 7/IM + Vehicle and IM + DKT (19 mg/kg) group. Columns indicate mean ± SEM. ## and *: significantly different from normal and IM + Vehicle at P < 0.01 and P < 0.05, respectively
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig4: Ameliorative effects of DKT on MPO-stained neutrophil infiltration in IM. a Indicates representative results for whole mount immunohistochemical staining of myenteric plexus region to detect MPO-positive neutrophils. b Shows quantification of neutrophil cells in n = 5/normal and IM + DKT (95 mg/kg) group, n = 7/IM + Vehicle and IM + DKT (19 mg/kg) group. Columns indicate mean ± SEM. ## and *: significantly different from normal and IM + Vehicle at P < 0.01 and P < 0.05, respectively
Mentions: After DKT treatment, we immunohistochemically monitored changes in MPO-stained neutrophils, and CD68-positive resident and monocyte-derived macrophages, as shown in Figs. 4 and 5. In Fig. 4, MPO-stained neutrophil infiltration into the ileal muscle layer was increased in the IM + Vehicle group, as compared with that in the normal group. Neutrophil infiltration by IM was significantly ameliorated in the IM + DKT group. In Fig. 5, resident dendritic macrophages [30] stained by CD68 were present in the myenteric plexus region in normal intestine [26, 31]. At 24 h after IM, many infiltrating monocyte-derived macrophages and activated round [30] resident macrophages were observed, as reported previously [5]. The CD68-positive macrophage population increased 6-fold in the inflamed ileal muscle layer of the intestine of the IM + Vehicle group, as compared with the normal group. The increased CD68-positive macrophage population was significantly inhibited in the IM + DKT group, as compared with the IM group. However, DKT had no effects on MPO-stained neutrophils or CD68-positive macrophages in the control ileal muscle layer (MPO-positive cells: normal, 3.26 ± 1.46 cells/mm2, +DKT, 4.88 ± 1.49 cells/mm2; CD68-positive cells: normal, 646.16 ± 16.59 cells/mm2, +DKT, 626.63 ± 29.52 cells/mm2). Neutrophil infiltration and increased CD68-positive macrophage population by IM was significantly ameliorated in manufactured DKT, m-DKT treated group as it was in our hand-made DKT (MPO-positive cells: normal 1.05 ± 0.39 cells/mm2, IM 1653.66 ± 121.24 cells/mm2, IM + DKT 1047.47 ± 92.27 cells/mm2, P < 0.05, IM + m-DKT 603.0 ± 90.70 cells/mm2, P < 0.01, n = 4; CD68-positive cells: normal 186.71 ± 13.15 cells/mm2, IM 2095.99 ± 144.04 cells/mm2, IM + DKT 1484.53 ± 70.11 cells/mm2, P < 0.05, IM + m-DKT 1515.12 ± 71.51 cells/mm2, P < 0.05, n = 4).Fig. 4

Bottom Line: Several mechanisms for the amelioration of POI by DKT have been suggested; however, it has remained unclear whether DKT shows anti-inflammatory effects in POI.DKT significantly inhibited the infiltration of neutrophils and CD68-positive macrophages, and inhibited mRNA expressions of TNF-α and MCP-1.In conclusion, in addition to the gastrointestinal prokinetic action, DKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Research, Oriental Medicine Research Center, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan.

ABSTRACT

Background: Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal medicine, is prescribed for patients with postoperative ileus (POI) and adhesive bowel obstruction following abdominal surgery. Several mechanisms for the amelioration of POI by DKT have been suggested; however, it has remained unclear whether DKT shows anti-inflammatory effects in POI. In the present study, we investigated the effects of DKT in a mouse POI model and attempted to clarify the detailed mechanisms of action.

Method: Intestinal manipulation (IM) was applied to the distal ileum of mice. DKT was administered orally to the animals 4 times before and after IM. Gastrointestinal transit in vivo, leukocyte infiltration, cytokine mRNA expression and gastrointestinal motility were analyzed. We also investigated the effects of the α7nAChR antagonist methyllycaconitine citrate (MLA) on the DKT-mediated ameliorative action against POI, and we studied the effects of DKT on inflammatory activity in α7nAChR knockout mice.

Results: DKT treatment led to recovery of the delayed intestinal transit induced by IM. DKT significantly inhibited the infiltration of neutrophils and CD68-positive macrophages, and inhibited mRNA expressions of TNF-α and MCP-1. MLA significantly reduced the anti-inflammatory action of DKT, and the amelioration of macrophage infiltration by DKT was partially suppressed in α7nAChR knockout mice.

Conclusions: In conclusion, in addition to the gastrointestinal prokinetic action, DKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency. The DKT-induced anti-inflammatory activity may be partly mediated by activation of α7nAChR.

Show MeSH
Related in: MedlinePlus