The present study investigated the effects of the herbal medicine Dai-kenchu-to (DKCT) and its 4 individual ingredients on intestinal blood flow (IBF) in rats by laser Doppler flowmetry. Intraduodenal administration of DKCT (30, 100 and 300 mg/kg) increased IBF in a dose-dependent manner, whereas the mean arterial blood pressure was not affected. One of the ingredients in DKCT is dried ginger rhizome (150 mg/kg), whose main component is [6]-shogaol (2 mg/kg), both of which showed similar effects to those shown by DKCT, while the other ingredients in DKCT only slightly increased IBF or had no effect. The calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP (8-37), completely abolished the hyperemia induced by DKCT, dried ginger rhizome and [6]-shogaol. However, the vasoactive intestinal polypeptide (VIP) receptor antagonist, [4-Cl-DPhe6, Leul7]-VIP, and atropine were less inhibitory than CGRP (8-37), and the substance P (SP) receptor antagonist, spantide, had no effect. The present study demonstrated that DKCT and one of its active components, [6]-shogaol, produced an increase in IBF which was mainly mediated by CGRP and suggests that DKCT may be useful in the treatment of intestinal ischemia-related diseases.

ABSTRACT-To clarify the contractile mechanism of Dai-kenchu-to, the effects of hydroxy b -sanshool (an ingredient of Zanthoxylum fruit), Zanthoxylum fruit (a constituent herb of Dai-kenchu-to) and Daikenchu-to were studied in mucosa-free longitudinal muscle of guinea pig ileum. Hydroxy b -sanshool at 10 -7 -10 -5 g/ ml induced dose-related contractions accompanied by autonomous contraction and produced an initial contraction at a concentration of 10 -4 g/ml or more. The contraction induced by hydroxy b -sanshool (10 -5 g/ ml) was significantly inhibited by tetrodotoxin or the capsaicin-receptor antagonist capsazepine. Although atropine or the substance P antagonist spantide tended to inhibit the contraction, a combination of atropine and spantide almost abolished the contraction by hydroxy b-sanshool. The P2-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid did not affect hydroxy b-sanshool-induced contraction in the presence or absence of spantide. The tonic contractions by Zanthoxylum fruit (2´10 -4 g/ml) and Dai-kenchu-to (10 -3 g/ml) were significantly inhibited or tended to be inhibited by atropine, spantide, tetrodotoxin or capsazepine and were remarkably suppressed by the combination of atropine and spantide. These results suggested that acetylcholine release from intrinsic cholinergic nerves and tachykinins from sensory neurons are involved in the contractions induced by hydroxy b-sanshool and that tachykinins may be involved in the atropine-resistant contraction by Dai-kenchu-to.Keywords: Dai-kenchu-to, Zanthoxylum fruit, Hydroxy b-sanshool, Intestinal motility, Tachykinin Dai-kenchu-to (Da-Jian-Zhong-Tang in Chinese) is a traditional Chinese herbal medicine, called Kampo medicine in Japan, and is a mixture of Zanthoxylum fruit, ginseng, dried ginger root and malt sugar. This formula is known for clinical effects on intestinal obstruction subsequent to laparotomy (1, 2). In vivo studies have demonstrated that Dai-kenchu-to enhanced gastrointestinal motility in dogs and rabbits (2, 3), and prevented intestinal adhesion in rats (4). In experiments using isolated intestines, Daikenchu-to induced contractions in rabbit jejunum, guinea pig ileum and colon, and relaxed guinea pig gastric body (5 -8). These reports indicated that Zanthoxylum fruit induces contraction; however, the other constituent herbs had no significant contractile effect on the isolated intestine. In guinea pig ileum and colon, contractions due to Dai-kenchu-to and Zanthoxylum fruit are mediated by acetylcholine release from the ends of cholinergic nerves, and 5-HT4 receptors are involved (7,8). In addition, since we also noted that a mucosa-free preparation resists the contractile response to atropine (8), it was suggested that other neurotransmitters are involved in the contractile effect of Dai-kenchu-to.Hydroxy b-sanshool is considered to be one of the active compounds involved in inducing contraction by Zanthoxylum fruit (9, 10). It was reported that the contractile effect is due to the release of acetylch...

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