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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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Effect of DKT on excretion and cumulative excretion of 13CO2, as calculated by 13C-acetate breath test in POI model mice. a, b Showed excretion and cumulative excretion curves for 13CO2, respectively. Detailed procedures are described in “Materials and methods”. Open diamonds, closed squares, open triangles and open circles indicate normal, 24 h after IM, IM with 15 mg/kg DKT and IM with 95 mg/kg DKT groups, respectively. ## are significantly difference from normal (P < 0.01). Symbols indicate mean ± SEM of 5–7 experiments. ** are significantly different between IM group and IM + DKT group (19 and 95 mg/kg), respectively
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Fig3: Effect of DKT on excretion and cumulative excretion of 13CO2, as calculated by 13C-acetate breath test in POI model mice. a, b Showed excretion and cumulative excretion curves for 13CO2, respectively. Detailed procedures are described in “Materials and methods”. Open diamonds, closed squares, open triangles and open circles indicate normal, 24 h after IM, IM with 15 mg/kg DKT and IM with 95 mg/kg DKT groups, respectively. ## are significantly difference from normal (P < 0.01). Symbols indicate mean ± SEM of 5–7 experiments. ** are significantly different between IM group and IM + DKT group (19 and 95 mg/kg), respectively

Mentions: To further examine an effect of DKT on gastric emptying rate by measuring 13C-acetate breath test. Curves obtained for 13CO2 excretion in the two different doses of DKT + IM, IM and normal groups are shown in Fig. 3. Excretion (A) and cumulative excretion (B) of 13CO2 in the IM group were significantly lower than those in the normal group (P < 0.01 by ANOVA). At each time-point from 15 to 40 min, excretion of 13CO2 in the IM group was significantly lower (P < 0.01 each) than those of the normal group. At each time-point from 15 to 60 min, cumulative excretion of 13CO2 in the IM group was significantly lower (P < 0.01 each) than that in the normal group. The maximum concentration (Cmax; Δ ‰) (Normal; 55.24 ± 5.22, IM + vehicle; 21.23 ± 1.41, P < 0.05) and the aria under the curve (AUC; Δ ‰/min) (Normal; 1385.33 ± 221.31, IM + vehicle; 180.75 ± 18.71, P < 0.01) were significantly decreased and the time to reach the maximum concentration (Tmax; min) (Normal; 19.00 ± 0.94, IM + vehicle; 28.57 ± 1.71, P < 0.01) was significantly increased in IM.Fig. 3


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)

Effect of DKT on excretion and cumulative excretion of 13CO2, as calculated by 13C-acetate breath test in POI model mice. a, b Showed excretion and cumulative excretion curves for 13CO2, respectively. Detailed procedures are described in “Materials and methods”. Open diamonds, closed squares, open triangles and open circles indicate normal, 24 h after IM, IM with 15 mg/kg DKT and IM with 95 mg/kg DKT groups, respectively. ## are significantly difference from normal (P < 0.01). Symbols indicate mean ± SEM of 5–7 experiments. ** are significantly different between IM group and IM + DKT group (19 and 95 mg/kg), respectively
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Effect of DKT on excretion and cumulative excretion of 13CO2, as calculated by 13C-acetate breath test in POI model mice. a, b Showed excretion and cumulative excretion curves for 13CO2, respectively. Detailed procedures are described in “Materials and methods”. Open diamonds, closed squares, open triangles and open circles indicate normal, 24 h after IM, IM with 15 mg/kg DKT and IM with 95 mg/kg DKT groups, respectively. ## are significantly difference from normal (P < 0.01). Symbols indicate mean ± SEM of 5–7 experiments. ** are significantly different between IM group and IM + DKT group (19 and 95 mg/kg), respectively
Mentions: To further examine an effect of DKT on gastric emptying rate by measuring 13C-acetate breath test. Curves obtained for 13CO2 excretion in the two different doses of DKT + IM, IM and normal groups are shown in Fig. 3. Excretion (A) and cumulative excretion (B) of 13CO2 in the IM group were significantly lower than those in the normal group (P < 0.01 by ANOVA). At each time-point from 15 to 40 min, excretion of 13CO2 in the IM group was significantly lower (P < 0.01 each) than those of the normal group. At each time-point from 15 to 60 min, cumulative excretion of 13CO2 in the IM group was significantly lower (P < 0.01 each) than that in the normal group. The maximum concentration (Cmax; Δ ‰) (Normal; 55.24 ± 5.22, IM + vehicle; 21.23 ± 1.41, P < 0.05) and the aria under the curve (AUC; Δ ‰/min) (Normal; 1385.33 ± 221.31, IM + vehicle; 180.75 ± 18.71, P < 0.01) were significantly decreased and the time to reach the maximum concentration (Tmax; min) (Normal; 19.00 ± 0.94, IM + vehicle; 28.57 ± 1.71, P < 0.01) was significantly increased in IM.Fig. 3

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