Effects of Dai‐kenchu‐to, a herbal medicine, on uterine and intestinal motility

Murata, Pin; Hayakawa, Terumasa; Satoh, Kaneo; Kase, Yoshio; Ishige, Atsushi; Sasaki, Hiroshi

doi:10.1002/ptr.745

Cited by 21 publications

(15 citation statements)

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“…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).…”

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Mechanism of Atropine-Resistant Contraction Induced by Dai-kenchu-to in Guinea Pig Ileum

Satoh

Hashimoto

Hayakawa

et al. 2001

Japanese Journal of Pharmacology

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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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confidence: 99%

Mechanism of Atropine-Resistant Contraction Induced by Dai-kenchu-to in Guinea Pig Ileum

Satoh

Hashimoto

Hayakawa

et al. 2001

Japanese Journal of Pharmacology

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“…[2][3][4] We confirmed that the administration of Dai-kenchu-to causes significant increases in the levels of motilin, vasoactive intestinal polypeptide (VIP), serotonin, calcitonin gene-related peptide (CGRP), and substance P in human plasma. [5][6][7] These results indicate that the gastrointestinal motor activity of Dai-kenchu-to is closely related to changes in these neuropeptides in human plasma.…”

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confidence: 63%

Effects of Pirenzepine on Dai-kenchu-to-Induced Elevation of the Plasma Neuropeptide Levels in Humans

Sato

Inoue

Katagiri

et al. 2006

Biological & Pharmaceutical Bulletin

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Dai-kenchu-to (Da-Jian-Zhong-Tang), a traditional Japanese Kampo medicine, is prepared from three different Chinese crude drugs: ninjin (Ginseng radix), sanshou (Zanthoxyli fructus), and kankyou (Zingiberis siccaatum rhizome). Dai-kenchu-to has been used for the treatment of abdominal obstructions, including bowel obstructions and a feeling of coldness in the abdomen. Dai-kenchu-to has recently been evaluated for its clinical usefulness in the treatment and prevention of uncomplicated postoperative adhesive intestinal obstruction and its clinical efficacy has been reported.1) It has been reported that the action of Dai-kenchuto is related to both increments in gastrointestinal motility and intestinal blood flow. [2][3][4] We confirmed that the administration of Dai-kenchu-to causes significant increases in the levels of motilin, vasoactive intestinal polypeptide (VIP), serotonin, calcitonin gene-related peptide (CGRP), and substance P in human plasma. [5][6][7] These results indicate that the gastrointestinal motor activity of Dai-kenchu-to is closely related to changes in these neuropeptides in human plasma.Nervous mechanisms are important for the regulation of gastrointestinal motility and blood flow. A number of neuropeptides such as CGRP, substance P, and VIP have been localized immunohistochemically in sensory nerves innervating the gastrointestinal tract.8) The release of these peptides is controlled by acetylcholine (ACh) from the preganglionic fibers of the parasympathetic nerve.9-11) Muscarinic receptors are also present on the membrane of motilin-secreting cells, and ACh is a major regulator of motilin release in the gastrointestine. [12][13][14][15] Pirenzepine, an antagonist specific for muscarinic M 1 receptors, suppresses acid output and is used to treat gastritis and peptic ulcers clinically.16) It has also been shown that this drug suppresses the elevation of serum gastrin levels by acting directly or indirectly on gastrin cells (G cells). 17,18) In this study, we examined the effects of pirenzepine on Daikenchu-to-induced elevation of plasma gastrin-, motilin-, somatostatin-, VIP-, CGRP-, and substance P-immunoreactive substance (IS) levels and the area under the plasma neuropeptides concentration-time curve from 0 to 240 min (AUC 0→240 min ) in human volunteers. VOLUNTEERS, MATERIALS, AND METHODSMaterials Dai-kenchu-to (TJ-100), prepared as a dried extract powder of Ginseng radix (3.0 g), Zanthoxyli fructus (2.0 g), and Zingiberis siccaatum rhizome (5.0 g) were purchased from Tsumura Co. Ltd. (Tokyo, Japan). Pirenzepine (Gastrozepine tablets) was purchased from Boehringer Ingelheim Co. Ltd. (Hyogo, Japan). The placebo was excipient alone (glucose and maltose) for the above formulations.Synthetic human gastrin I (2-17) was purchased from Sigma Chemicals (St. Louis, MO, U.S.A.) and the VIP fragment peptide was supplied by Professor H. Yajima (Kyoto University, Kyoto, Japan). Antisera to gastrin (A600/R1B), VIP (A6054/R1B), and CGRP were purchased from Biogenesis (Poole, U.K.). Antisera to somatos...

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“…In addition, the increase in blood flow induced by TU-100 was antagonized by a CGRP antagonist, and partially antagonized by a vasoactive intestinal peptide antagonist and atropine. 2,6 In prior studies in humans, we previously showed that TU-100 tended to accelerate small bowel and ascending colon transit in healthy volunteers, and in a study in 45 females with functional constipation without evidence of rectal evacuation disorder. 7 Treatment for 28 days with TU-100, 5 g t.i.d.…”

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confidence: 94%

A Pilot Study of the Effect of Daikenchuto on Rectal Sensation in Patients with Irritable Bowel Syndrome

Acosta

Camilleri

Linker-Nord

et al. 2015

J Neurogastroenterol Motil

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Background/AimsDaikenchuto (TU 100), a botanical agent that modulates gastrointestinal nerves, is used in the treatment of motility and functional disorders. Our aim was to study the effects of TU-100 on rectal compliance and sensation in patients with irritable bowel syndrome (IBS). MethodsIn 20 patients per treatment arm, we conducted a single-center, randomized, parallel-group, double-blind, placebo-controlled, singledose pharmacodynamics study evaluating the effects of TU-100, 15 g (5 g t.i.d. [means 3 times a day]), for 14-16 consecutive days on rectal compliance and rectal sensation (thresholds and sensation ratings), all measured at baseline and on the last day of medication treatment. The primary endpoint was rectal sensation thresholds and sensation ratings in response to balloon distension at 32 mmHg. Secondary endpoints were rectal compliance, sensation thresholds, ratings and tone (fasting and postprandial), bowel pattern, abdominal pain (average and worst severity) and bloating scores, IBS quality of life and safety profile. ResultsRectal sensation ratings post-treatment were significantly associated with baseline (pre-treatment) ratings and with level of anxiety or stress recorded at the time of the sensation testing. There were no effects of TU-100 treatment on rectal sensation ratings, sensation thresholds, rectal fasting or postprandial tone, rectal compliance, bowel function, abdominal pain or bloating scores, or IBS quality of life. Conclusions

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Effects of Dai‐kenchu‐to, a herbal medicine, on uterine and intestinal motility

Cited by 21 publications

References 5 publications

Mechanism of Atropine-Resistant Contraction Induced by Dai-kenchu-to in Guinea Pig Ileum

Mechanism of Atropine-Resistant Contraction Induced by Dai-kenchu-to in Guinea Pig Ileum

Effects of Pirenzepine on Dai-kenchu-to-Induced Elevation of the Plasma Neuropeptide Levels in Humans

A Pilot Study of the Effect of Daikenchuto on Rectal Sensation in Patients with Irritable Bowel Syndrome

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