Possible involvement of the transient receptor potential vanilloid type 1 channel in postoperative adhesive obstruction and its prevention by a kampo (traditional Japanese) medicine, daikenchuto.

This study focused on the localization of transient receptor potential vanilloid type 1 (TRPV1) in the intestines in postoperative adhesion model rats and investigated the underlying mechanism for the anti-adhesion action of daikenchuto (DKT), especially in relation to TRPV1. Postoperative intestinal adhesion was induced by sprinkling talc in the small intestine. The expression of TRPV1 mRNA was examined by in situ hybridization and real-time RT-PCR. The effects of DKT and its major ingredient, hydroxy sanshool, with or without ruthenium red, a TRP-channel antagonist, on talc-induced intestinal adhesions were evaluated. The level of TRPV1 mRNA was higher in the adhesion regions of talc-treated rats than in normal small intestine of sham-operated rats. Localization of TRPV1 mRNA expression was identified in the submucosal plexus of both sham-operated and talc-treated rats; and in talc-treated rats, it was observed also in the myenteric plexus and regions of adhesion. Capsaicin, DKT, and hydroxy sanshool significantly prevented formation of intestinal adhesions. The effects of DKT and hydroxy sanshool were abrogated by subcutaneous injection of ruthenium red. These results suggest that pharmacological modulation of TRPV1 might be a possible therapeutic option in postoperative intestinal adhesion, which might be relevant to the prevention of postoperative adhesive obstruction by DKT.

The pharmacological effects of Daikenchuto, a traditional herbal medicine, on delayed gastrointestinal transit in rat postoperative ileus.

The effect of Daikenchuto, a traditional herbal medicine, on gastrointestinal hypoperistalsis in postoperative ileus (POI) was investigated. POI was induced by laparotomy with manipulation of the gastrointestine under anesthesia, and gastrointestinal transit was calculated by migration of Evans blue. Daikenchuto (270 - 2,700 mg/kg, p.o.) dose-dependently improved the delayed gastrointestinal transit in POI. This effect of Daikenchuto was partially inhibited by SB204070 (1 mg/kg, s.c.), a 5-hydroxytriptamine(4) (5-HT(4))-receptor antagonist and completely abolished by atropine (1 mg/kg, s.c.), a muscarine-receptor antagonist. Among the constituents of Daikenchuto, the medical herb zanthoxylum fruit (60 mg/kg, p.o.) and maltose syrup (2,400 mg/kg, p.o.) significantly ameliorated the delayed gastrointestinal transit, but ginseng and processed ginger did not affect the gastrointestinal transit in the rat POI. The improvement induced by zanthoxylum fruit was also inhibited by atropine or SB204070. In addition, the high osmotic pressure of the maltose syrup (2400 mg/10 mL per kg) was related to the improvement of delayed gastrointestinal transit. These results demonstrated that Daikenchuto ameliorates postoperative hypoperistalsis via cholinergic nerves and 5-HT(4) receptors and that osmotic pressure also may be involved in this action. Moreover, zanthoxylum fruit and maltose syrup were crucial medical herbs contributing to the ability of Daikenchuto.

Effect of Dai-kenchu-to (Da-Jian-Zhong-Tang) on the delayed intestinal propulsion induced by chlorpromazine in mice.

This study was conducted to evaluate the effect of Dai-kenchu-to on chlorpromazine-induced hypoperistalsis in mice. Oral administration of Dai-kenchu-to (30-300 mg/kg) dose-dependently improved small intestinal and distal colonic propulsion decreased by chlorpromazine (3 mg/kg, p.o.). Although the improvement of small intestinal propulsion due to Dai-kenchu-to was partially inhibited by atropine (1 mg/kg, s.c.), this action was completely inhibited by the concomitant administration of lorglumide (10 mg/kg, i.p.), a CCKA receptor antagonist. The distal colonic propulsion-improving effect of Dai-kenchu-to was abolished by atropine (1 mg/kg, s.c.). When the effects of the respective components of Dai-kenchu-to were evaluated, oral administration of Zanthoxylum Fruit improved both delayed small intestinal and distal colonic propulsion caused by chlorpromazine. On the other hand, Malt Sugar was effective against only delayed small intestinal propulsion. The action of Zanthoxylum Fruit was completely inhibited by atropine (1 mg/kg, s.c.), and the effect of Malt Sugar was inhibited by lorglumide (10 mg/kg, i.p.). These results demonstrated that Dai-kenchu-to improves chlorpromazine-induced hypoperistalsis via cholinergic systems and that Zanthoxylum Fruit is the main contributor to this action of Dai-kenchu-to. In addition, endogenous CCK due to Malt Sugar may also contribute to this effect of Dai-kenchu-to.

Components of Panax ginseng that improve accelerated small intestinal transit.

We previously clarified that Dai-kenchu-to, a Chinese prescription, was useful for improving carbachol-induced hyperperistalsis of the small intestine in vivo, and the efficacy of Ginseng Radix, a crude drug component of Dai-kenchu-to, was also confirmed. Ginseng Radix, the root of Panax ginseng C.A. Meyer, showed significant ameliorative effects on both the carbachol-induced and the BaCl(2)-induced accelerated small intestinal transit model in mice, suggesting that both an inhibitory effect on the cholinergic nervous system and direct suppressive effect on muscles were involved in the ameliorative effect of Ginseng Radix on the accelerated small intestinal transit. Ginsenoside Rb1 (4) and ginsenoside Rd (7), major components of Ginseng Radix, improved both animal models. These results suggest that ginsenoside Rb1 (4) and ginsenoside Rd (7) were representative compounds of Ginseng Radix for improving the accelerated movement of the small intestine and that these compounds partly contribute to the action of Dai-kenchu-to on small intestinal transit.

Component of Zingiber officinale that improves the enhancement of small intestinal transport.

6-Shogaol, a constituent of Zingiber officinale, improved carbachol-induced accelerated small intestinal transit in vivo, as well as improving longitudinal muscle contraction induced by low-frequency electrical stimulation of the isolated guinea pig small intestine in vitro. In addition, 6-shogaol ameliorated BaCl(2) -induced hyperperistalsis of the small intestine in vivo.