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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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Related in: MedlinePlus

Effects of DKT on mRNA expression of inflammatory mediators in inflamed muscle layer of small intestine in mouse POI model. a Showed typical results of RT-PCR. b–f Showed quantitative results of mRNA expression of TNF-α, IL-6, IL-1β, MCP-1 and iNOS. Bars indicate mean ± SEM from n = 4/group. # and ##; significantly different from normal at P < 0.05 and P < 0.01, respectively. *: significantly different from IM + Vehicle at P < 0.05
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Fig6: Effects of DKT on mRNA expression of inflammatory mediators in inflamed muscle layer of small intestine in mouse POI model. a Showed typical results of RT-PCR. b–f Showed quantitative results of mRNA expression of TNF-α, IL-6, IL-1β, MCP-1 and iNOS. Bars indicate mean ± SEM from n = 4/group. # and ##; significantly different from normal at P < 0.05 and P < 0.01, respectively. *: significantly different from IM + Vehicle at P < 0.05

Mentions: As shown in Fig. 6, mRNA expressions of MCP-1 and TNF-α were significantly elevated in the IM + Vehicle group. IL-6 and iNOS genes also showed an upward trend in IM (Dunnet’s test values: IL-6; P = 0.06, iNOS; P = 0.44). mRNA expression of TNF-α and MCP-1 were significantly inhibited in the IM + DKT group, as compared with the IM + Vehicle group. The IM-induced increase in IL-6 and iNOS mRNA expressions also showed a downward trend in DKT-treated mice (Dunnet’s test values: IL-6; P = 0.25, iNOS; P = 0.29).Fig. 6


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)

Effects of DKT on mRNA expression of inflammatory mediators in inflamed muscle layer of small intestine in mouse POI model. a Showed typical results of RT-PCR. b–f Showed quantitative results of mRNA expression of TNF-α, IL-6, IL-1β, MCP-1 and iNOS. Bars indicate mean ± SEM from n = 4/group. # and ##; significantly different from normal at P < 0.05 and P < 0.01, respectively. *: significantly different from IM + Vehicle at P < 0.05
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig6: Effects of DKT on mRNA expression of inflammatory mediators in inflamed muscle layer of small intestine in mouse POI model. a Showed typical results of RT-PCR. b–f Showed quantitative results of mRNA expression of TNF-α, IL-6, IL-1β, MCP-1 and iNOS. Bars indicate mean ± SEM from n = 4/group. # and ##; significantly different from normal at P < 0.05 and P < 0.01, respectively. *: significantly different from IM + Vehicle at P < 0.05
Mentions: As shown in Fig. 6, mRNA expressions of MCP-1 and TNF-α were significantly elevated in the IM + Vehicle group. IL-6 and iNOS genes also showed an upward trend in IM (Dunnet’s test values: IL-6; P = 0.06, iNOS; P = 0.44). mRNA expression of TNF-α and MCP-1 were significantly inhibited in the IM + DKT group, as compared with the IM + Vehicle group. The IM-induced increase in IL-6 and iNOS mRNA expressions also showed a downward trend in DKT-treated mice (Dunnet’s test values: IL-6; P = 0.25, iNOS; P = 0.29).Fig. 6

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