Daikenchuto

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Toru Kono - One of the best experts on this subject based on the ideXlab platform.

  • Daikenchuto, a traditional Japanese herbal medicine, promotes colonic transit by inducing a propulsive movement pattern.
    Neurogastroenterology and Motility, 2019
    Co-Authors: Kunitsugu Kubota, Toru Kono, Yuji Morine, Masahiro Yamamoto, Akihito Mase, Hiroaki Matsushima, Naoki Fujitsuka, Akinobu Taketomi, Mitsuo Shimada
    Abstract:

    BACKGROUND The traditional Japanese herbal medicine, Daikenchuto (DKT), has been used to treat constipation and postoperative ileus. However, the precise mechanisms involved in the pharmacological effects of DKT remain uncertain. The aim of this study was to clarify the effect of DKT on motor patterns and transit activity in the isolated rat colon. METHODS The entire colon or segments of the proximal colon in rats were isolated and placed in Krebs solution. The motility of the colon was evaluated by analyzing spatiotemporal maps of diameter derived from video imaging and measuring the intraluminal pressure in the anal end of the proximal colon, and the transit time of a plastic bead through the entire isolated colon. KEY RESULTS Several types of propagating contractions were observed in the isolated entire colon. When DKT was added to Krebs solution, the frequency of large-extent anal propagating contractions increased. DKT treatment increased the intraluminal pressure in the isolated proximal colon, which was related to the propagating contractions. This effect was abolished by treatment with the neural blocker tetrodotoxin. These findings suggest DKT induced peristaltic contractions in the isolated colon. DKT accelerated colonic transit activity, which was related to peristaltic contractions induction in the colon. These effects were also observed in the colons treated with bethanechol and the active ingredient of DKT, hydroxy-α-sanshool. CONCLUSIONS AND INFERENCES Daikenchuto could enhance colonic transit activity by inducing peristaltic contractions, which may be mediated by the activation of the enteric nervous system in the colon.

  • Efficacy of Daikenchuto for the intestinal hypomotility after open abdominal surgery: A pooled analysis of three randomized controlled trials.
    Journal of Clinical Oncology, 2018
    Co-Authors: Toru Kono, Hidetoshi Katsuno, Koutarou Maeda, Satoshi Morita, Mitsuo Shimada, Yuji Morine, Kozo Yoshikawa, Keisuke Koeda, Masaaki Nishi, Masahiko Watanabe
    Abstract:

    801Background: Postoperative intestinal hypomotility (IH) is very common after open abdominal (OAS) surgery. Although several advances have been made in medical therapy, very few recognized treatment or prevention methods are currently available. Daikenchuto (DKT), a traditional Japanese prescribed medicine, peripherally stimulates the neurogenic pathway, attempted to reduce postoperative IH in three exploratory randomized controlled trials (RCT). For further analysis of whether DKT accelerates IH recovery after scheduled OAS we conducted a pooled analysis of three RCTs. Methods: A pooled retrospective subset analysis of OAS patients with colon, liver, or gastric cancer in DKT RCTs was performed; RCTs were supported by the Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC). Among all patients enrolled and randomized in the three RCTs (JFMC project numbers 39-0902, 40-1001, and 42-1002), 740 patients who were eligible were included for the efficacy analysis. The modified intent-to-treat p...

  • Daikenchuto tu 100 alters murine hepatic and intestinal drug metabolizing enzymes in an in vivo dietary model effects of gender and withdrawal
    Pharmacology Research & Perspectives, 2017
    Co-Authors: Kentaro Nobutani, Toru Kono, Junko Watanabe, Atsushi Kaneko, Masahiro Yamamoto, Mitsue Nishiyama, Jun Miyoshi, Mark W Musch, Masaru Yoshida, Hyunyoung Jeong
    Abstract:

    Herbal medicines and natural products used for maintenance of health or treatment of diseases have many biological effects, including altering the pharmacokinetics and metabolism of other medications. Daikenchuto (TU-100), an aqueous extract of ginger, ginseng, and Japanese green pepper fruit, is a commonly prescribed Kampo (Japanese herbal medicine) for postoperative ileus or bloating. The effects of TU-100 on drug metabolism have not been investigated. In this study, we analyzed the effect of TU-100 on expression of key drug-metabolizing enzymes (DMEs) and drug transporters (DTs) in murine liver and gastrointestinal tract using a dietary model. Liver, jejunum, and proximal colon were analyzed for phase I and II DMEs and DT mRNA expression by reverse transcription (RT) first by nonquantitative and followed by quantitative polymerase chain reaction (PCR) and protein expression. Liver, jejunum, and proximal colon expressed some identical but also unique DMEs and DTs. TU-100 increased the greatest changes in cytochrome (Cyp) 2b10 and Cyp3a11 and Mdr1a. Basal and TU-100 stimulated levels of DME and DT expression were gender-dependent, dose-dependent and reversible after cessation of TU-100 supplementation, except for some changes in the intestine. Quantitative Western blot analysis of protein extracts confirmed the quantitative PCR results.

  • C-jun N-terminal kinase dependent autophagic cell death in cancer cells induced by Zanthoxylum fruit extract from Japanese pepper.
    Journal of Clinical Oncology, 2017
    Co-Authors: Toru Kono, Reo Nozaki, Hiroki Bochimoto, Tsuyoshi Watanabe, Kaori Oketani, Yuichi Sakamaki, Naoto Okubo, Koji Nakagawa, Hiroshi Takeda
    Abstract:

    653Background: Natural products constitute a promising resource for drug development including an anticancer drug. Zanthoxylum fruit, obtained from the Japanese pepper plant (Zanthoxylum piperitum De Candolle), and its extract (Zanthoxylum fruit extract, ZFE) is an important component of Daikenchuto, which is a form of Japanese traditional medicine. Recently, we have reported that Daikenchuto has an anticancer activity in vivo, however precise mechanism is still unclear. Therefore, we investigated the potential anticancer activity of ZFE as an inducer of autophagic cell death (ACD). Methods: ZFE powder was provided by Tsumura (Japan). We investigated the effect of ZFE on the morphology of six types of human cancer cells and normal cells by using phase contrast microscopy and electron microscopy. Knockdown of autophagy-related gene 5 (ATG5), which is an essential gene for autophagy, by transfecting small interfering RNA was performed and confirmed by quantitative RT-qPCR and Western blot analysis. Effect o...

  • Daikenchuto tu 100 suppresses tumor development in the azoxymethane and apcmin mouse models of experimental colon cancer
    Phytotherapy Research, 2017
    Co-Authors: Atsushi Kaneko, Masahiro Yamamoto, Jun Miyoshi, Daina L. Ringus, Takumu Hasebe, Jun Matsukawa, John Hart, Toru Kono
    Abstract:

    Chemopreventative properties of traditional medicines and underlying mechanisms of action are incompletely investigated. This study demonstrates that dietary Daikenchuto (TU-100), comprised of ginger, ginseng, and Japanese pepper effectively suppresses intestinal tumor development and progression in the azoxymethane (AOM) and APCmin/+ mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30 weeks. APCmin/+ mice were fed diet without or with TU-100 starting at 6 weeks, and sacrificed at 24 weeks. In both models, dietary TU-100 decreased tumor size. In APC min/+ mice, the number of small intestinal tumors was significantly decreased. In the AOM model, both TU-100 and Japanese ginseng decreased colon tumor numbers. Decreased Ki-67 and β-catenin immunostaining and activation of numerous transduction pathways involved in tumor initiation and progression were observed. EGF receptor expression and stimulation/phosphorylation in vitro were investigated in C2BBe1 cells. TU-100, ginger, and 6-gingerol suppressed EGF receptor induced Akt activation. TU-100 and ginseng and to a lesser extent ginger or 6-gingerol inhibited EGF ERK1/2 activation. TU-100 and some of its components and metabolites of these components inhibit tumor progression in two mouse models of colon cancer by blocking downstream pathways of EGF receptor activation. Copyright © 2016 John Wiley & Sons, Ltd.

Masahiro Yamamoto - One of the best experts on this subject based on the ideXlab platform.

  • Daikenchuto, a traditional Japanese herbal medicine, promotes colonic transit by inducing a propulsive movement pattern.
    Neurogastroenterology and Motility, 2019
    Co-Authors: Kunitsugu Kubota, Toru Kono, Yuji Morine, Masahiro Yamamoto, Akihito Mase, Hiroaki Matsushima, Naoki Fujitsuka, Akinobu Taketomi, Mitsuo Shimada
    Abstract:

    BACKGROUND The traditional Japanese herbal medicine, Daikenchuto (DKT), has been used to treat constipation and postoperative ileus. However, the precise mechanisms involved in the pharmacological effects of DKT remain uncertain. The aim of this study was to clarify the effect of DKT on motor patterns and transit activity in the isolated rat colon. METHODS The entire colon or segments of the proximal colon in rats were isolated and placed in Krebs solution. The motility of the colon was evaluated by analyzing spatiotemporal maps of diameter derived from video imaging and measuring the intraluminal pressure in the anal end of the proximal colon, and the transit time of a plastic bead through the entire isolated colon. KEY RESULTS Several types of propagating contractions were observed in the isolated entire colon. When DKT was added to Krebs solution, the frequency of large-extent anal propagating contractions increased. DKT treatment increased the intraluminal pressure in the isolated proximal colon, which was related to the propagating contractions. This effect was abolished by treatment with the neural blocker tetrodotoxin. These findings suggest DKT induced peristaltic contractions in the isolated colon. DKT accelerated colonic transit activity, which was related to peristaltic contractions induction in the colon. These effects were also observed in the colons treated with bethanechol and the active ingredient of DKT, hydroxy-α-sanshool. CONCLUSIONS AND INFERENCES Daikenchuto could enhance colonic transit activity by inducing peristaltic contractions, which may be mediated by the activation of the enteric nervous system in the colon.

  • Time-, Sex-, and Dose-Dependent Alterations of the Gut Microbiota by Consumption of Dietary Daikenchuto (TU-100)
    Evidence-based Complementary and Alternative Medicine, 2018
    Co-Authors: Jun Miyoshi, Yoshio Kase, Masahiro Yamamoto, Mitsue Nishiyama, Kentaro Nobutani, Mark W Musch, Daina L. Ringus, Nathaniel Hubert, Eugene B. Chang
    Abstract:

    Medications or dietary components can affect both the host and the host’s gut microbiota. Changes in the microbiota may influence medication efficacy and interactions. Daikenchuto (TU-100), a herbal medication, comprised of ginger, ginseng, and Japanese pepper, is widely used in Japanese traditional Kampo medicine for intestinal motility and postoperative paralytic ileus. We previously showed in mice that consumption of TU-100 for 4 weeks changed the gut microbiota and increased bioavailability of bacterial ginsenoside metabolites. Since TU-100 is prescribed in humans for months to years, we examined the time- and sex-dependent effects of TU-100 on mouse gut microbiota. Oral administration of 1.5% TU-100 for 24 weeks caused more pronounced changes in gut microbiota in female than in male mice. Changes in both sexes largely reverted to baseline upon TU-100 withdrawal. Effects were time and dose dependent. The microbial profiles reverted to baseline within 4 weeks after withdrawal of 0.75% TU-100 but were sustained after withdrawal of 3% TU-100. In summary, dietary TU-100 changed mouse microbiota in a time-, sex-, and dose-dependent manner. These findings may be taken into consideration when determining optimizing dose for conditions of human health and disease with the consideration of differences in composition and response of the human intestinal microbiota.

  • Daikenchuto tu 100 alters murine hepatic and intestinal drug metabolizing enzymes in an in vivo dietary model effects of gender and withdrawal
    Pharmacology Research & Perspectives, 2017
    Co-Authors: Kentaro Nobutani, Toru Kono, Junko Watanabe, Atsushi Kaneko, Masahiro Yamamoto, Mitsue Nishiyama, Jun Miyoshi, Mark W Musch, Masaru Yoshida, Hyunyoung Jeong
    Abstract:

    Herbal medicines and natural products used for maintenance of health or treatment of diseases have many biological effects, including altering the pharmacokinetics and metabolism of other medications. Daikenchuto (TU-100), an aqueous extract of ginger, ginseng, and Japanese green pepper fruit, is a commonly prescribed Kampo (Japanese herbal medicine) for postoperative ileus or bloating. The effects of TU-100 on drug metabolism have not been investigated. In this study, we analyzed the effect of TU-100 on expression of key drug-metabolizing enzymes (DMEs) and drug transporters (DTs) in murine liver and gastrointestinal tract using a dietary model. Liver, jejunum, and proximal colon were analyzed for phase I and II DMEs and DT mRNA expression by reverse transcription (RT) first by nonquantitative and followed by quantitative polymerase chain reaction (PCR) and protein expression. Liver, jejunum, and proximal colon expressed some identical but also unique DMEs and DTs. TU-100 increased the greatest changes in cytochrome (Cyp) 2b10 and Cyp3a11 and Mdr1a. Basal and TU-100 stimulated levels of DME and DT expression were gender-dependent, dose-dependent and reversible after cessation of TU-100 supplementation, except for some changes in the intestine. Quantitative Western blot analysis of protein extracts confirmed the quantitative PCR results.

  • Daikenchuto tu 100 suppresses tumor development in the azoxymethane and apcmin mouse models of experimental colon cancer
    Phytotherapy Research, 2017
    Co-Authors: Atsushi Kaneko, Masahiro Yamamoto, Jun Miyoshi, Daina L. Ringus, Takumu Hasebe, Jun Matsukawa, John Hart, Toru Kono
    Abstract:

    Chemopreventative properties of traditional medicines and underlying mechanisms of action are incompletely investigated. This study demonstrates that dietary Daikenchuto (TU-100), comprised of ginger, ginseng, and Japanese pepper effectively suppresses intestinal tumor development and progression in the azoxymethane (AOM) and APCmin/+ mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30 weeks. APCmin/+ mice were fed diet without or with TU-100 starting at 6 weeks, and sacrificed at 24 weeks. In both models, dietary TU-100 decreased tumor size. In APC min/+ mice, the number of small intestinal tumors was significantly decreased. In the AOM model, both TU-100 and Japanese ginseng decreased colon tumor numbers. Decreased Ki-67 and β-catenin immunostaining and activation of numerous transduction pathways involved in tumor initiation and progression were observed. EGF receptor expression and stimulation/phosphorylation in vitro were investigated in C2BBe1 cells. TU-100, ginger, and 6-gingerol suppressed EGF receptor induced Akt activation. TU-100 and ginseng and to a lesser extent ginger or 6-gingerol inhibited EGF ERK1/2 activation. TU-100 and some of its components and metabolites of these components inhibit tumor progression in two mouse models of colon cancer by blocking downstream pathways of EGF receptor activation. Copyright © 2016 John Wiley & Sons, Ltd.

  • Daikenchuto (TU‐100) Suppresses Tumor Development in the Azoxymethane and APCmin/+ Mouse Models of Experimental Colon Cancer
    Phytotherapy Research, 2016
    Co-Authors: Takumu Hasebe, Toru Kono, Atsushi Kaneko, Masahiro Yamamoto, Jun Miyoshi, Daina L. Ringus, Mikihiro Fujiya, Jun Matsukawa, John Hart, Yutaka Kohgo
    Abstract:

    Chemopreventative properties of traditional medicines and underlying mechanisms of action are incompletely investigated. This study demonstrates that dietary Daikenchuto (TU-100), comprised of ginger, ginseng, and Japanese pepper effectively suppresses intestinal tumor development and progression in the azoxymethane (AOM) and APCmin/+ mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30 weeks. APCmin/+ mice were fed diet without or with TU-100 starting at 6 weeks, and sacrificed at 24 weeks. In both models, dietary TU-100 decreased tumor size. In APC min/+ mice, the number of small intestinal tumors was significantly decreased. In the AOM model, both TU-100 and Japanese ginseng decreased colon tumor numbers. Decreased Ki-67 and β-catenin immunostaining and activation of numerous transduction pathways involved in tumor initiation and progression were observed. EGF receptor expression and stimulation/phosphorylation in vitro were investigated in C2BBe1 cells. TU-100, ginger, and 6-gingerol suppressed EGF receptor induced Akt activation. TU-100 and ginseng and to a lesser extent ginger or 6-gingerol inhibited EGF ERK1/2 activation. TU-100 and some of its components and metabolites of these components inhibit tumor progression in two mouse models of colon cancer by blocking downstream pathways of EGF receptor activation. Copyright © 2016 John Wiley & Sons, Ltd.

Yoshiharu Sakai - One of the best experts on this subject based on the ideXlab platform.

  • The Cochrane Library - Daikenchuto for reducing postoperative ileus in patients undergoing elective abdominal surgery
    Cochrane Database of Systematic Reviews, 2020
    Co-Authors: Nobuaki Hoshino, Toshihiko Takada, Koya Hida, Suguru Hasegawa, Toshi A Furukawa, Yoshiharu Sakai
    Abstract:

    Background Postoperative ileus is a major complication for persons undergoing abdominal surgery. Daikenchuto, a Japanese traditional medicine (Kampo), is a drug that may reduce postoperative ileus. Objectives To assess the efficacy and safety of Daikenchuto for reducing prolonged postoperative ileus in persons undergoing elective abdominal surgery. Search methods We searched the following databases on 3 July 2017: CENTRAL, MEDLINE, Embase, ICHUSHI, WHO (World Health Organization) International Clinical Trials Registry Platform (ICTRP), EU Crinical Trials registry (EU-CTR), UMIN Clinical Trials Registry (UMIN-CTR), ClinicalTrials.gov, The Japan Society for Oriental Medicine (JSOM), American Society of Clinical Oncology (ASCO), Society of American Gastrointestinal and Endscopic Surgeons (SAGES). We set no limitations on language or date of publication. Selection criteria We included randomised controlled trials (RCTs) comparing Daikenchuto with any control condition in adults, 18 years of age or older, undergoing elective abdominal surgery. Data collection and analysis We applied standard methodological procedures expected by Cochrane. Two review authors independently reviewed the articles identified by literature searches, extracted data, and assessed risk of bias of the included studies using the Cochrane software Review Manager 5. Main results We included seven RCTs with a total of 1202 participants. Overall, we judged the risk of bias as low in four studies and high in three studies. We are uncertain whether Daikenchuto reduced time to first flatus (mean difference (MD) -11.32 hours, 95% confidence interval (CI) -17.45 to -5.19; two RCTs, 83 participants; very low-quality evidence), or time to first bowel movement (MD -9.44 hours, 95% CI -22.22 to 3.35; four RCTs, 500 participants; very low-quality evidence) following surgery. There was little or no difference in time to resumption of regular solid food following surgery (MD 3.64 hours, 95% CI -24.45 to 31.74; two RCTs, 258 participants; low-quality evidence). There were no adverse events in either arm of the five RCTs that reported on drug-related adverse events (risk difference (RD) 0.00, 95% CI -0.02 to 0.02, 568 participants, low-quality evidence). We are uncertain of the effect of Daikenchuto on patient satisfaction (MD 0.09, 95% CI -0.19 to 0.37; one RCT, 81 participants; very low-quality of evidence). There was little or no difference in the incidence of any re-interventions for postoperative ileus before leaving hospital (risk ratio (RR) 0.99, 95% CI 0.06 to 15.62; one RCT, 207 participants; moderate-quality evidence), or length of hospital stay (MD -0.49 days, 95% CI -1.21 to 0.22; three RCTs, 292 participants; low-quality evidence). Authors' conclusions Evidence from current literature was unclear whether Daikenchuto reduced postoperative ileus in patients undergoing elective abdominal surgery, due to the small number of participants in the meta-analyses. Very low-quality evidence means we are uncertain whether Daikenchuto improved postoperative flatus or bowel movement. Further well-designed and adequately powered studies are needed to assess the efficacy of Daikenchuto.

  • Daikenchuto for reducing postoperative ileus in patients undergoing elective abdominal surgery.
    The Cochrane database of systematic reviews, 2018
    Co-Authors: Nobuaki Hoshino, Toshihiko Takada, Koya Hida, Suguru Hasegawa, Toshi A Furukawa, Yoshiharu Sakai
    Abstract:

    Postoperative ileus is a major complication for persons undergoing abdominal surgery. Daikenchuto, a Japanese traditional medicine (Kampo), is a drug that may reduce postoperative ileus. To assess the efficacy and safety of Daikenchuto for reducing prolonged postoperative ileus in persons undergoing elective abdominal surgery. We searched the following databases on 3 July 2017: CENTRAL, MEDLINE, Embase, ICHUSHI, WHO (World Health Organization) International Clinical Trials Registry Platform (ICTRP), EU Crinical Trials registry (EU-CTR), UMIN Clinical Trials Registry (UMIN-CTR), ClinicalTrials.gov, The Japan Society for Oriental Medicine (JSOM), American Society of Clinical Oncology (ASCO), Society of American Gastrointestinal and Endscopic Surgeons (SAGES). We set no limitations on language or date of publication. We included randomised controlled trials (RCTs) comparing Daikenchuto with any control condition in adults, 18 years of age or older, undergoing elective abdominal surgery. We applied standard methodological procedures expected by Cochrane. Two review authors independently reviewed the articles identified by literature searches, extracted data, and assessed risk of bias of the included studies using the Cochrane software Review Manager 5. We included seven RCTs with a total of 1202 participants. Overall, we judged the risk of bias as low in four studies and high in three studies. We are uncertain whether Daikenchuto reduced time to first flatus (mean difference (MD) -11.32 hours, 95% confidence interval (CI) -17.45 to -5.19; two RCTs, 83 participants; very low-quality evidence), or time to first bowel movement (MD -9.44 hours, 95% CI -22.22 to 3.35; four RCTs, 500 participants; very low-quality evidence) following surgery. There was little or no difference in time to resumption of regular solid food following surgery (MD 3.64 hours, 95% CI -24.45 to 31.74; two RCTs, 258 participants; low-quality evidence). There were no adverse events in either arm of the five RCTs that reported on drug-related adverse events (risk difference (RD) 0.00, 95% CI -0.02 to 0.02, 568 participants, low-quality evidence). We are uncertain of the effect of Daikenchuto on patient satisfaction (MD 0.09, 95% CI -0.19 to 0.37; one RCT, 81 participants; very low-quality of evidence). There was little or no difference in the incidence of any re-interventions for postoperative ileus before leaving hospital (risk ratio (RR) 0.99, 95% CI 0.06 to 15.62; one RCT, 207 participants; moderate-quality evidence), or length of hospital stay (MD -0.49 days, 95% CI -1.21 to 0.22; three RCTs, 292 participants; low-quality evidence). Evidence from current literature was unclear whether Daikenchuto reduced postoperative ileus in patients undergoing elective abdominal surgery, due to the small number of participants in the meta-analyses. Very low-quality evidence means we are uncertain whether Daikenchuto improved postoperative flatus or bowel movement. Further well-designed and adequately powered studies are needed to assess the efficacy of Daikenchuto.

  • Enhanced anastomotic healing by Daikenchuto (TJ-100) in rats
    Scientific Reports, 2018
    Co-Authors: Toshiaki Wada, Suguru Hasegawa, Kenji Kawada, Kenjiro Hirai, Kosuke Toda, Masayoshi Iwamoto, Yoshiharu Sakai
    Abstract:

    Daikenchuto (DKT), a traditional Japanese medicine, is widely used to treat various gastrointestinal disorders. This study aimed to investigate whether DKT could promote the anastomotic healing in a rat model. Pedicled colonic segments were made in left colon by ligation of the feeding arteries, and then intestinal continuity was restored. Colonic blood flow was analyzed by using ICG fluorescence imaging: Fmax, Tmax, T1/2, and Slope were calculated. Anastomotic leakage (AL) was found in 6 of 19 rats (31.6%) in the control group, whereas in 1 of 16 rats (6.2%) in the DKT group. The Fmax and Slope of DKT group were significantly higher than those of control group. DKT could promote the anastomotic healing, with the higher bursting pressure on postoperative day (POD) 2 and 5, the larger granulation thickness on POD 5, and neoangiogenesis on POD 5. Histological examination showed DKT exhibited a decreased inflammatory cell infiltration, enhanced fibroblast infiltration, and enhanced collagen density on POD 5. In the DKT group, the levels of TGFβ1 on POD 2 and VEGFα on POD5 were significantly higher, whereas the level of TNFα on POD 2 was significantly lower. Therefore, DKT could be effective for the prevention of AL following colorectal surgery.

  • Daikenchuto for reducing postoperative ileus in patients undergoing elective abdominal surgery
    Cochrane Database of Systematic Reviews, 2016
    Co-Authors: Nobuaki Hoshino, Toshihiko Takada, Koya Hida, Suguru Hasegawa, Toshi A Furukawa, Yoshiharu Sakai
    Abstract:

    Reason for withdrawal: Serious breach of Cochrane's conflict of interest policy. A ruling by Cochrane's Funding Arbiters that a Cochrane Review has seriously breached Cochrane's conflict of interest policy.

Atsushi Kaneko - One of the best experts on this subject based on the ideXlab platform.

  • Daikenchuto tu 100 alters murine hepatic and intestinal drug metabolizing enzymes in an in vivo dietary model effects of gender and withdrawal
    Pharmacology Research & Perspectives, 2017
    Co-Authors: Kentaro Nobutani, Toru Kono, Junko Watanabe, Atsushi Kaneko, Masahiro Yamamoto, Mitsue Nishiyama, Jun Miyoshi, Mark W Musch, Masaru Yoshida, Hyunyoung Jeong
    Abstract:

    Herbal medicines and natural products used for maintenance of health or treatment of diseases have many biological effects, including altering the pharmacokinetics and metabolism of other medications. Daikenchuto (TU-100), an aqueous extract of ginger, ginseng, and Japanese green pepper fruit, is a commonly prescribed Kampo (Japanese herbal medicine) for postoperative ileus or bloating. The effects of TU-100 on drug metabolism have not been investigated. In this study, we analyzed the effect of TU-100 on expression of key drug-metabolizing enzymes (DMEs) and drug transporters (DTs) in murine liver and gastrointestinal tract using a dietary model. Liver, jejunum, and proximal colon were analyzed for phase I and II DMEs and DT mRNA expression by reverse transcription (RT) first by nonquantitative and followed by quantitative polymerase chain reaction (PCR) and protein expression. Liver, jejunum, and proximal colon expressed some identical but also unique DMEs and DTs. TU-100 increased the greatest changes in cytochrome (Cyp) 2b10 and Cyp3a11 and Mdr1a. Basal and TU-100 stimulated levels of DME and DT expression were gender-dependent, dose-dependent and reversible after cessation of TU-100 supplementation, except for some changes in the intestine. Quantitative Western blot analysis of protein extracts confirmed the quantitative PCR results.

  • Daikenchuto tu 100 suppresses tumor development in the azoxymethane and apcmin mouse models of experimental colon cancer
    Phytotherapy Research, 2017
    Co-Authors: Atsushi Kaneko, Masahiro Yamamoto, Jun Miyoshi, Daina L. Ringus, Takumu Hasebe, Jun Matsukawa, John Hart, Toru Kono
    Abstract:

    Chemopreventative properties of traditional medicines and underlying mechanisms of action are incompletely investigated. This study demonstrates that dietary Daikenchuto (TU-100), comprised of ginger, ginseng, and Japanese pepper effectively suppresses intestinal tumor development and progression in the azoxymethane (AOM) and APCmin/+ mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30 weeks. APCmin/+ mice were fed diet without or with TU-100 starting at 6 weeks, and sacrificed at 24 weeks. In both models, dietary TU-100 decreased tumor size. In APC min/+ mice, the number of small intestinal tumors was significantly decreased. In the AOM model, both TU-100 and Japanese ginseng decreased colon tumor numbers. Decreased Ki-67 and β-catenin immunostaining and activation of numerous transduction pathways involved in tumor initiation and progression were observed. EGF receptor expression and stimulation/phosphorylation in vitro were investigated in C2BBe1 cells. TU-100, ginger, and 6-gingerol suppressed EGF receptor induced Akt activation. TU-100 and ginseng and to a lesser extent ginger or 6-gingerol inhibited EGF ERK1/2 activation. TU-100 and some of its components and metabolites of these components inhibit tumor progression in two mouse models of colon cancer by blocking downstream pathways of EGF receptor activation. Copyright © 2016 John Wiley & Sons, Ltd.

  • Daikenchuto (TU‐100) Suppresses Tumor Development in the Azoxymethane and APCmin/+ Mouse Models of Experimental Colon Cancer
    Phytotherapy Research, 2016
    Co-Authors: Takumu Hasebe, Toru Kono, Atsushi Kaneko, Masahiro Yamamoto, Jun Miyoshi, Daina L. Ringus, Mikihiro Fujiya, Jun Matsukawa, John Hart, Yutaka Kohgo
    Abstract:

    Chemopreventative properties of traditional medicines and underlying mechanisms of action are incompletely investigated. This study demonstrates that dietary Daikenchuto (TU-100), comprised of ginger, ginseng, and Japanese pepper effectively suppresses intestinal tumor development and progression in the azoxymethane (AOM) and APCmin/+ mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30 weeks. APCmin/+ mice were fed diet without or with TU-100 starting at 6 weeks, and sacrificed at 24 weeks. In both models, dietary TU-100 decreased tumor size. In APC min/+ mice, the number of small intestinal tumors was significantly decreased. In the AOM model, both TU-100 and Japanese ginseng decreased colon tumor numbers. Decreased Ki-67 and β-catenin immunostaining and activation of numerous transduction pathways involved in tumor initiation and progression were observed. EGF receptor expression and stimulation/phosphorylation in vitro were investigated in C2BBe1 cells. TU-100, ginger, and 6-gingerol suppressed EGF receptor induced Akt activation. TU-100 and ginseng and to a lesser extent ginger or 6-gingerol inhibited EGF ERK1/2 activation. TU-100 and some of its components and metabolites of these components inhibit tumor progression in two mouse models of colon cancer by blocking downstream pathways of EGF receptor activation. Copyright © 2016 John Wiley & Sons, Ltd.

  • TU-100 (Daikenchuto) and Ginger Ameliorate Anti-CD3 Antibody Induced T Cell-Mediated Murine Enteritis: Microbe-Independent Effects Involving Akt and NF-kB Suppression
    2016
    Co-Authors: Nobuhiro Ueno, Toru Kono, Atsushi Kaneko, Masahiro Yamamoto, Takumu Hasebe, Mikihiro Fujiya, Yutaka Kohgo, Chong-zhi Wang, Chun-su Yuan, Marc Bissonnette
    Abstract:

    The Japanese traditional medicine Daikenchuto (TU-100) has anti-inflammatory activities, but the mechanisms remain incompletely understood. TU-100 includes ginger, ginseng, and Japanese pepper, each component possessing bioactive properties. The effects of TU-100 and individual components were investigated in a model of intestinal T lymphocyte activation using anti-CD3 antibody. To determine contribution of intestinal bacteria, specific pathogen free (SPF) and germ free (GF) mice were used. TU-100 or its components were delivered by diet or by gavage. Anti-CD3 antibody increased jejunal accumulation of fluid, increased TNFa, and induced intestinal epithelial apoptosis in both SPF and GF mice, which was blocked by either TU-100 or ginger, but not by ginseng or Japanese pepper. TU-100 and ginger also blocked anti-CD3-stimulated Akt and NF-kB activation. A co-culture system of colonic Caco2BBE and Jurkat-1 cells was used to examine T-lymphocyte/epithelial cells interactions. Jurkat-1 cells were stimulated with anti-CD3 to produce TNFa that activates epithelial cell NF-kB. TU-100 and ginger blocked anti-CD3 antibody activation of Akt in Jurkat cells, decreasing their TNFa production. Additionally, TU-100 and ginger alone blocked direct TNFa stimulation of Caco2BBE cells and decrease

  • in Mice: Possible Involvement of Enhancing Adrenomedullin in Intestinal Epithelial Cells
    2016
    Co-Authors: Atsushi Kaneko, Toru Kono, Naoko Miura, Naoko Tsuchiya, Masahiro Yamamoto
    Abstract:

    Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Purpose. Crohn’s disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD), have histopathologically and immunologically different characteristics. We previously reported that a traditional Japanese medicine, Daikenchuto (TU-100), ameliorated a trinitrobenzenesulfonic acid- (TNBS-) induced type-1 model colitis exhibiting histopathological features of CD through adrenomedullin (ADM) enhancement. Our current aims were to examine whether TU-100 ameliorates a type-2 model colitis that histologically resembles UC and identify the active ingredients. Methods. TU-100 was administered orally to mice with oxazolone- (OXN-) induced type-2 model colitis. The morbidity was evaluated by body weight loss and the macroscopic score of colonic lesions. ADM was quantified using an EIA kit. Results. TU-100 prevented weight loss and colon ulceration. ADM production by intestinal epithelial cells was increased by TU-100 addition. Screening to identify active ingredients showed that [6]-shogaol and hydrox

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  • Daikenchuto tu 100 suppresses tumor development in the azoxymethane and apcmin mouse models of experimental colon cancer
    Phytotherapy Research, 2017
    Co-Authors: Atsushi Kaneko, Masahiro Yamamoto, Jun Miyoshi, Daina L. Ringus, Takumu Hasebe, Jun Matsukawa, John Hart, Toru Kono
    Abstract:

    Chemopreventative properties of traditional medicines and underlying mechanisms of action are incompletely investigated. This study demonstrates that dietary Daikenchuto (TU-100), comprised of ginger, ginseng, and Japanese pepper effectively suppresses intestinal tumor development and progression in the azoxymethane (AOM) and APCmin/+ mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30 weeks. APCmin/+ mice were fed diet without or with TU-100 starting at 6 weeks, and sacrificed at 24 weeks. In both models, dietary TU-100 decreased tumor size. In APC min/+ mice, the number of small intestinal tumors was significantly decreased. In the AOM model, both TU-100 and Japanese ginseng decreased colon tumor numbers. Decreased Ki-67 and β-catenin immunostaining and activation of numerous transduction pathways involved in tumor initiation and progression were observed. EGF receptor expression and stimulation/phosphorylation in vitro were investigated in C2BBe1 cells. TU-100, ginger, and 6-gingerol suppressed EGF receptor induced Akt activation. TU-100 and ginseng and to a lesser extent ginger or 6-gingerol inhibited EGF ERK1/2 activation. TU-100 and some of its components and metabolites of these components inhibit tumor progression in two mouse models of colon cancer by blocking downstream pathways of EGF receptor activation. Copyright © 2016 John Wiley & Sons, Ltd.

  • Daikenchuto (TU‐100) Suppresses Tumor Development in the Azoxymethane and APCmin/+ Mouse Models of Experimental Colon Cancer
    Phytotherapy Research, 2016
    Co-Authors: Takumu Hasebe, Toru Kono, Atsushi Kaneko, Masahiro Yamamoto, Jun Miyoshi, Daina L. Ringus, Mikihiro Fujiya, Jun Matsukawa, John Hart, Yutaka Kohgo
    Abstract:

    Chemopreventative properties of traditional medicines and underlying mechanisms of action are incompletely investigated. This study demonstrates that dietary Daikenchuto (TU-100), comprised of ginger, ginseng, and Japanese pepper effectively suppresses intestinal tumor development and progression in the azoxymethane (AOM) and APCmin/+ mouse models. For the AOM model, TU-100 was provided after the first of six biweekly AOM injections. Mice were sacrificed at 30 weeks. APCmin/+ mice were fed diet without or with TU-100 starting at 6 weeks, and sacrificed at 24 weeks. In both models, dietary TU-100 decreased tumor size. In APC min/+ mice, the number of small intestinal tumors was significantly decreased. In the AOM model, both TU-100 and Japanese ginseng decreased colon tumor numbers. Decreased Ki-67 and β-catenin immunostaining and activation of numerous transduction pathways involved in tumor initiation and progression were observed. EGF receptor expression and stimulation/phosphorylation in vitro were investigated in C2BBe1 cells. TU-100, ginger, and 6-gingerol suppressed EGF receptor induced Akt activation. TU-100 and ginseng and to a lesser extent ginger or 6-gingerol inhibited EGF ERK1/2 activation. TU-100 and some of its components and metabolites of these components inhibit tumor progression in two mouse models of colon cancer by blocking downstream pathways of EGF receptor activation. Copyright © 2016 John Wiley & Sons, Ltd.

  • TU-100 (Daikenchuto) and Ginger Ameliorate Anti-CD3 Antibody Induced T Cell-Mediated Murine Enteritis: Microbe-Independent Effects Involving Akt and NF-kB Suppression
    2016
    Co-Authors: Nobuhiro Ueno, Toru Kono, Atsushi Kaneko, Masahiro Yamamoto, Takumu Hasebe, Mikihiro Fujiya, Yutaka Kohgo, Chong-zhi Wang, Chun-su Yuan, Marc Bissonnette
    Abstract:

    The Japanese traditional medicine Daikenchuto (TU-100) has anti-inflammatory activities, but the mechanisms remain incompletely understood. TU-100 includes ginger, ginseng, and Japanese pepper, each component possessing bioactive properties. The effects of TU-100 and individual components were investigated in a model of intestinal T lymphocyte activation using anti-CD3 antibody. To determine contribution of intestinal bacteria, specific pathogen free (SPF) and germ free (GF) mice were used. TU-100 or its components were delivered by diet or by gavage. Anti-CD3 antibody increased jejunal accumulation of fluid, increased TNFa, and induced intestinal epithelial apoptosis in both SPF and GF mice, which was blocked by either TU-100 or ginger, but not by ginseng or Japanese pepper. TU-100 and ginger also blocked anti-CD3-stimulated Akt and NF-kB activation. A co-culture system of colonic Caco2BBE and Jurkat-1 cells was used to examine T-lymphocyte/epithelial cells interactions. Jurkat-1 cells were stimulated with anti-CD3 to produce TNFa that activates epithelial cell NF-kB. TU-100 and ginger blocked anti-CD3 antibody activation of Akt in Jurkat cells, decreasing their TNFa production. Additionally, TU-100 and ginger alone blocked direct TNFa stimulation of Caco2BBE cells and decrease

  • Daikenchuto (TU‐100) shapes gut microbiota architecture and increases the production of ginsenoside metabolite compound K
    Pharmacology Research & Perspectives, 2016
    Co-Authors: Takumu Hasebe, Toru Kono, Junko Watanabe, Atsushi Kaneko, Masahiro Yamamoto, Mark W Musch, Nobuhiro Ueno, Noriko Kaifuchi, Anuradha Nadimpalli, Yuhei Inaba
    Abstract:

    Many pharmaceutical agents not only require microbial metabolism for increased bioavailability and bioactivity, but also have direct effects on gut microbial assemblage and function. We examined the possibility that these actions are not mutually exclusive and may be mutually reinforcing in ways that enhance long-term of these agents. Daikenchuto, TU-100, is a traditional Japanese medicine containing ginseng. Conversion of the ginsenoside Rb1 (Rb1) to bioactive compound K (CK) requires bacterial metabolism. Diet-incorporated TU-100 was administered to mice over a period of several weeks. T-RFLP and 454 pyrosequencing were performed to analyze the time-dependent effects on fecal microbial membership. Fecal microbial capacity to metabolize Rb1 to CK was measured by adding TU-100 or ginseng to stool samples to assess the generation of bioactive metabolites. Levels of metabolized TU-100 components in plasma and in stool samples were measured by LC-MS/MS. Cecal and stool short-chain fatty acids were measured by GC-MS. Dietary administration of TU-100 for 28 days altered the gut microbiota, increasing several bacteria genera including members of Clostridia and Lactococcus lactis. Progressive capacity of microbiota to convert Rb1 to CK was observed over the 28 days administration of dietary TU-100. Concomitantly with these changes, increases in all SCFA were observed in cecal contents and in acetate and butyrate content of the stool. Chronic consumption of dietary TU-100 promotes changes in gut microbiota enhancing metabolic capacity of TU-100 and increased bioavailability. We believe these findings have broad implications in optimizing the efficacy of natural compounds that depend on microbial bioconversion in general.

  • TU-100 (Daikenchuto) and ginger ameliorate anti-CD3 antibody induced T cell-mediated murine enteritis: microbe-independent effects involving Akt and NF-κB suppression.
    PLOS ONE, 2014
    Co-Authors: Nobuhiro Ueno, Toru Kono, Atsushi Kaneko, Masahiro Yamamoto, Takumu Hasebe, Mikihiro Fujiya, Yutaka Kohgo, Chong-zhi Wang, Chun-su Yuan, Marc Bissonnette
    Abstract:

    The Japanese traditional medicine Daikenchuto (TU-100) has anti-inflammatory activities, but the mechanisms remain incompletely understood. TU-100 includes ginger, ginseng, and Japanese pepper, each component possessing bioactive properties. The effects of TU-100 and individual components were investigated in a model of intestinal T lymphocyte activation using anti-CD3 antibody. To determine contribution of intestinal bacteria, specific pathogen free (SPF) and germ free (GF) mice were used. TU-100 or its components were delivered by diet or by gavage. Anti-CD3 antibody increased jejunal accumulation of fluid, increased TNFα, and induced intestinal epithelial apoptosis in both SPF and GF mice, which was blocked by either TU-100 or ginger, but not by ginseng or Japanese pepper. TU-100 and ginger also blocked anti-CD3-stimulated Akt and NF-κB activation. A co-culture system of colonic Caco2BBE and Jurkat-1 cells was used to examine T-lymphocyte/epithelial cells interactions. Jurkat-1 cells were stimulated with anti-CD3 to produce TNFα that activates epithelial cell NF-κB. TU-100 and ginger blocked anti-CD3 antibody activation of Akt in Jurkat cells, decreasing their TNFα production. Additionally, TU-100 and ginger alone blocked direct TNFα stimulation of Caco2BBE cells and decreased activation of caspase-3 and polyADP ribose. The present studies demonstrate a new anti-inflammatory action of TU-100 that is microbe-independent and due to its ginger component.