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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 action of DKT on gastrointestinal transit in mouse POI model. Detailed procedures are described in “Materials and methods. ” a Shows distribution of PR in the normal group (left panel), at 24 h after IM + Vehicle (middle panel) and after IM + DKT (95 mg/kg, right panel). Columns indicate mean ± SEM of n = 4/group. b, c Show geometric center and gastric emptying rate, as calculated from a. Bars indicate mean ± SEM. ##; significantly different from normal at P < 0.01. * and ** are significantly different from IM + Vehicle at P < 0.05 and P < 0.01, respectively
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Fig2: Ameliorative action of DKT on gastrointestinal transit in mouse POI model. Detailed procedures are described in “Materials and methods. ” a Shows distribution of PR in the normal group (left panel), at 24 h after IM + Vehicle (middle panel) and after IM + DKT (95 mg/kg, right panel). Columns indicate mean ± SEM of n = 4/group. b, c Show geometric center and gastric emptying rate, as calculated from a. Bars indicate mean ± SEM. ##; significantly different from normal at P < 0.01. * and ** are significantly different from IM + Vehicle at P < 0.05 and P < 0.01, respectively

Mentions: The effects of DKT on delayed intestinal transit in the mouse POI model are summarized in Fig. 2. Approximately 6 % of the orally administered labeled phenol red (PR) remained inside the stomach, while 94 % was transported down the intestine to the distal end of the ileum, peaking at SI-8 in the normal group (Fig. 2a). The average calculated geometric center and gastric emptying rate in the normal group were 7.16 ± 0.22 and 94.42 ± 0.85 % for the 15 segments of the gastrointestinal tract, respectively (Fig. 2b, c). In the IM + Vehicle group, approximately 44 % of the orally administered labeled PR remained inside the stomach, while 56 % was transported to SI-1 and SI-2 (Fig. 2a). The IM group showed significantly delayed rates for the geometric center at 2.04 ± 0.07 and gastric emptying at 55.56 ± 4.13, as compared with the normal group (Fig. 2b, c). The IM + DKT (95 mg/kg) group showed significant recovery of the delayed intestinal transit caused by IM, in which 22 % of the orally administered content remained in the stomach, while 78 % of the transported content moved between SI-1 and SI-3, peaking in SI-3 (Fig. 2a). Both the geometric center and gastric emptying rate in IM + DKT (95 mg/kg) were significantly higher, reaching 4.11 ± 0.37 and 84.13 ± 2.60, respectively (Fig. 2b, c). In normal mice, DKT slightly but significantly increased intestinal transit and gastric emptying rate (Geometric center: normal, 7.15 ± 0.15, +DKT, 9.53 ± 0.78, P < 0.05; Gastric emptying rate: normal 94.96 ± 0.63 %, +DKT, 99.70 ± 0.22 %, P < 0.05, n = 3–5), thus suggesting the prokinetic potential of DKT under the current experimental conditions.Fig. 2


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 action of DKT on gastrointestinal transit in mouse POI model. Detailed procedures are described in “Materials and methods. ” a Shows distribution of PR in the normal group (left panel), at 24 h after IM + Vehicle (middle panel) and after IM + DKT (95 mg/kg, right panel). Columns indicate mean ± SEM of n = 4/group. b, c Show geometric center and gastric emptying rate, as calculated from a. Bars indicate mean ± SEM. ##; significantly different from normal at P < 0.01. * and ** are significantly different from IM + Vehicle at P < 0.05 and P < 0.01, respectively
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig2: Ameliorative action of DKT on gastrointestinal transit in mouse POI model. Detailed procedures are described in “Materials and methods. ” a Shows distribution of PR in the normal group (left panel), at 24 h after IM + Vehicle (middle panel) and after IM + DKT (95 mg/kg, right panel). Columns indicate mean ± SEM of n = 4/group. b, c Show geometric center and gastric emptying rate, as calculated from a. Bars indicate mean ± SEM. ##; significantly different from normal at P < 0.01. * and ** are significantly different from IM + Vehicle at P < 0.05 and P < 0.01, respectively
Mentions: The effects of DKT on delayed intestinal transit in the mouse POI model are summarized in Fig. 2. Approximately 6 % of the orally administered labeled phenol red (PR) remained inside the stomach, while 94 % was transported down the intestine to the distal end of the ileum, peaking at SI-8 in the normal group (Fig. 2a). The average calculated geometric center and gastric emptying rate in the normal group were 7.16 ± 0.22 and 94.42 ± 0.85 % for the 15 segments of the gastrointestinal tract, respectively (Fig. 2b, c). In the IM + Vehicle group, approximately 44 % of the orally administered labeled PR remained inside the stomach, while 56 % was transported to SI-1 and SI-2 (Fig. 2a). The IM group showed significantly delayed rates for the geometric center at 2.04 ± 0.07 and gastric emptying at 55.56 ± 4.13, as compared with the normal group (Fig. 2b, c). The IM + DKT (95 mg/kg) group showed significant recovery of the delayed intestinal transit caused by IM, in which 22 % of the orally administered content remained in the stomach, while 78 % of the transported content moved between SI-1 and SI-3, peaking in SI-3 (Fig. 2a). Both the geometric center and gastric emptying rate in IM + DKT (95 mg/kg) were significantly higher, reaching 4.11 ± 0.37 and 84.13 ± 2.60, respectively (Fig. 2b, c). In normal mice, DKT slightly but significantly increased intestinal transit and gastric emptying rate (Geometric center: normal, 7.15 ± 0.15, +DKT, 9.53 ± 0.78, P < 0.05; Gastric emptying rate: normal 94.96 ± 0.63 %, +DKT, 99.70 ± 0.22 %, P < 0.05, n = 3–5), thus suggesting the prokinetic potential of DKT under the current experimental conditions.Fig. 2

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