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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 and negative effects of MLA on MPO activity and MPO-positive neutrophil infiltration in mouse POI model. a, c Show representative images of MPO-positive neutrophil infiltration into myenteric plexus region and quantification results from n = 4/normal and IM + Vehicle group, n = 5/IM + DKT + MLA group. b Shows results for MPO activity. Columns indicate mean ± SEM from n = 4/group. ##: significantly different from normal at P < 0.01. * and ** are significantly different from IM at P < 0.05, P < 0.01.ψ: significantly different between IM + DKT and IM + DKT + MLA at P < 0.05
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Fig7: Ameliorative effects of DKT and negative effects of MLA on MPO activity and MPO-positive neutrophil infiltration in mouse POI model. a, c Show representative images of MPO-positive neutrophil infiltration into myenteric plexus region and quantification results from n = 4/normal and IM + Vehicle group, n = 5/IM + DKT + MLA group. b Shows results for MPO activity. Columns indicate mean ± SEM from n = 4/group. ##: significantly different from normal at P < 0.01. * and ** are significantly different from IM at P < 0.05, P < 0.01.ψ: significantly different between IM + DKT and IM + DKT + MLA at P < 0.05

Mentions: The effects of MLA on anti-inflammatory activity of DKT in the mouse POI model are summarized in Figs. 7 and 8. As shown in Fig. 6b and c, MLA partly attenuated anti-inflammatory activity by DKT, as tissue MPO activity and MPO-positive neutrophil numbers were inhibited when compared with the IM + Vehicle group, respectively.Fig. 7


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 and negative effects of MLA on MPO activity and MPO-positive neutrophil infiltration in mouse POI model. a, c Show representative images of MPO-positive neutrophil infiltration into myenteric plexus region and quantification results from n = 4/normal and IM + Vehicle group, n = 5/IM + DKT + MLA group. b Shows results for MPO activity. Columns indicate mean ± SEM from n = 4/group. ##: significantly different from normal at P < 0.01. * and ** are significantly different from IM at P < 0.05, P < 0.01.ψ: significantly different between IM + DKT and IM + DKT + MLA at P < 0.05
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4048467&req=5

Fig7: Ameliorative effects of DKT and negative effects of MLA on MPO activity and MPO-positive neutrophil infiltration in mouse POI model. a, c Show representative images of MPO-positive neutrophil infiltration into myenteric plexus region and quantification results from n = 4/normal and IM + Vehicle group, n = 5/IM + DKT + MLA group. b Shows results for MPO activity. Columns indicate mean ± SEM from n = 4/group. ##: significantly different from normal at P < 0.01. * and ** are significantly different from IM at P < 0.05, P < 0.01.ψ: significantly different between IM + DKT and IM + DKT + MLA at P < 0.05
Mentions: The effects of MLA on anti-inflammatory activity of DKT in the mouse POI model are summarized in Figs. 7 and 8. As shown in Fig. 6b and c, MLA partly attenuated anti-inflammatory activity by DKT, as tissue MPO activity and MPO-positive neutrophil numbers were inhibited when compared with the IM + Vehicle group, respectively.Fig. 7

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