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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- and CD68-positive neutrophils and macrophage infiltration in wild-type and α7nAChR KO mice. a, b Show the effects of DKT on MPO-positive neutrophil and CD68-positive macrophage infiltration induced by IM, respectively. Columns represent mean ± SEM from n = 7/wild-type mice, n = 8/normal and IM + Vehicle group in α7nAChR KO mice, n = 9/IM + DKT group in α7nAChR KO mice. Wild-type mice are C57BL/6J mice and α7nAChR KO mice are of C57BL/6J background. ##: significantly different from normal at P < 0.01. * and **: significantly different between IM and IM + DKT at P < 0.05 and P < 0.01, respectively. ψψ: significantly different between wild-type mice and α7nAChR KO mice at P < 0.01
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Fig9: Ameliorative effects of DKT on MPO- and CD68-positive neutrophils and macrophage infiltration in wild-type and α7nAChR KO mice. a, b Show the effects of DKT on MPO-positive neutrophil and CD68-positive macrophage infiltration induced by IM, respectively. Columns represent mean ± SEM from n = 7/wild-type mice, n = 8/normal and IM + Vehicle group in α7nAChR KO mice, n = 9/IM + DKT group in α7nAChR KO mice. Wild-type mice are C57BL/6J mice and α7nAChR KO mice are of C57BL/6J background. ##: significantly different from normal at P < 0.01. * and **: significantly different between IM and IM + DKT at P < 0.05 and P < 0.01, respectively. ψψ: significantly different between wild-type mice and α7nAChR KO mice at P < 0.01

Mentions: Figure 9 shows the anti-inflammatory activity of DKT in α7nAChR KO mice, with reference to that in wild-type mice (C57BL/6J). In wild-type mice, the MPO-positive infiltrating neutrophil and CD68-positive macrophage populations increased in the IM + Vehicle group, as was seen in BALB/c mice, and these increases were significantly inhibited in the IM + DKT group, as compared with the IM + Vehicle group.Fig. 9


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- and CD68-positive neutrophils and macrophage infiltration in wild-type and α7nAChR KO mice. a, b Show the effects of DKT on MPO-positive neutrophil and CD68-positive macrophage infiltration induced by IM, respectively. Columns represent mean ± SEM from n = 7/wild-type mice, n = 8/normal and IM + Vehicle group in α7nAChR KO mice, n = 9/IM + DKT group in α7nAChR KO mice. Wild-type mice are C57BL/6J mice and α7nAChR KO mice are of C57BL/6J background. ##: significantly different from normal at P < 0.01. * and **: significantly different between IM and IM + DKT at P < 0.05 and P < 0.01, respectively. ψψ: significantly different between wild-type mice and α7nAChR KO mice at P < 0.01
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Related In: Results  -  Collection

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Fig9: Ameliorative effects of DKT on MPO- and CD68-positive neutrophils and macrophage infiltration in wild-type and α7nAChR KO mice. a, b Show the effects of DKT on MPO-positive neutrophil and CD68-positive macrophage infiltration induced by IM, respectively. Columns represent mean ± SEM from n = 7/wild-type mice, n = 8/normal and IM + Vehicle group in α7nAChR KO mice, n = 9/IM + DKT group in α7nAChR KO mice. Wild-type mice are C57BL/6J mice and α7nAChR KO mice are of C57BL/6J background. ##: significantly different from normal at P < 0.01. * and **: significantly different between IM and IM + DKT at P < 0.05 and P < 0.01, respectively. ψψ: significantly different between wild-type mice and α7nAChR KO mice at P < 0.01
Mentions: Figure 9 shows the anti-inflammatory activity of DKT in α7nAChR KO mice, with reference to that in wild-type mice (C57BL/6J). In wild-type mice, the MPO-positive infiltrating neutrophil and CD68-positive macrophage populations increased in the IM + Vehicle group, as was seen in BALB/c mice, and these increases were significantly inhibited in the IM + DKT group, as compared with the IM + Vehicle group.Fig. 9

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