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Iijima S. Use of Traditional Japanese Herbal Medicine Daikenchuto for the Treatment of Abdominal Distention in Very-Low-Birth-Weight Infants. J Clin Med 2024; 13:5082. [PMID: 39274296 PMCID: PMC11396189 DOI: 10.3390/jcm13175082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 08/08/2024] [Accepted: 08/23/2024] [Indexed: 09/16/2024] Open
Abstract
Background: Very-low-birth-weight (VLBW) infants often experience feeding intolerance owing to organ immaturity, and the most frequent sign is the presence of abdominal distention. Daikenchuto (DKT), a traditional Japanese herbal medicine, is used to improve gastrointestinal function, particularly in adults. The aim of this study was to investigate the effectiveness of DKT in reducing abdominal distention and intestinal gas in VLBW infants. Methods: This study involved a retrospective chart review of 24 VLBW infants treated with DKT at Hamamatsu University Hospital between April 2016 and March 2021. The effects of DKT treatment at a dose of 0.3 g/kg/day were evaluated through clinical parameters and abdominal radiography. Results: Before treatment, marked abdominal distention was observed in 46% of the infants, which reduced to 4% within a week of DKT administration. The gas volume score (GVS) decreased in 92% of the patients within the first week of treatment and markedly decreased by ≥20% in 46% of the patients. The effects of improving abdominal distention and decreasing the GVS on radiography persisted for 1-2 weeks after treatment initiation. No clinical parameters affecting a GVS reduction of ≥20% and no notable adverse effects were observed. Conclusions: While the preliminary findings suggest that DKT may help manage abdominal distention in VLBW infants, further studies with placebo-controlled trials, larger sample sizes, use of advanced image processing software, and consideration of additional influencing factors are required to substantiate these results and identify predictors of treatment response.
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Affiliation(s)
- Shigeo Iijima
- Department of Regional Neonatal-Perinatal Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
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Mitani T, Yawata Y, Yamamoto N, Nishide M, Sakamoto H, Kayano SI. Stability of Hydroxy-α-Sanshool in Medium-Chain Triglyceride Oil and Corresponding Oil/Water Emulsions. Foods 2023; 12:3589. [PMID: 37835243 PMCID: PMC10572447 DOI: 10.3390/foods12193589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 09/25/2023] [Accepted: 09/26/2023] [Indexed: 10/15/2023] Open
Abstract
The pungent component of sansho (Japanese pepper, Zanthoxylum pipritum) is sanshool, which is easily oxidized and decomposed. We have previously reported several sanshool stabilizers, such as α-tocopherol (α-Toc). Sansho pericarp powder treated with middle-chain triglycerides (MCTs) can be used to obtain extracts containing hydroxy-α-sanshool (HαS). Although HαS is stabilized when α-Toc is added to the MCT extracts, the loss of HαS is accelerated when it is mixed with a powder such as lactose. The separation of α-Toc from sanshools was thought to inevitably lead to their oxidation. Therefore, using sansho pericarp MCT extracts with or without α-Toc, oil/water (o/w) emulsions were prepared by adding a surfactant, glycerin, and water to these extracts. In both emulsions, HαS was stable in accelerated tests at 50 °C. However, when lactose powder was added to the emulsions and an accelerated test was performed, HαS in the emulsion containing α-Toc was stable, but HαS in the emulsion without α-Toc was unstable. These results highlight the importance of maintaining the close proximity of HαS and α-Toc in the emulsion. The stabilization of sanshools using emulsion technology can facilitate the production of various processed beverages, foods, cosmetics, and pharmaceuticals containing Japanese pepper.
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Affiliation(s)
- Takahiko Mitani
- Center of Regional Revitalization, Research Center for Food and Agriculture, Wakayama University, Wakayama 640-8510, Japan
| | - Yasuko Yawata
- Center of Regional Revitalization, Research Center for Food and Agriculture, Wakayama University, Wakayama 640-8510, Japan
| | - Nami Yamamoto
- Faculty of Education, Wakayama University, Wakayama 640-8510, Japan;
| | - Mitsunori Nishide
- Division of Food and Nutrition, Wakayama Shin-Ai Women’s Junior College, Wakayama 640-0341, Japan;
| | - Hidefumi Sakamoto
- Faculty of Systems Engineering, Wakayama University, Wakayama 640-8510, Japan;
| | - Shin-ichi Kayano
- Department of Nutrition, Faculty of Health Science, Kio University, Nara 635-0832, Japan;
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Mitani T, Yawata Y, Yamamoto N, Okuno Y, Sakamoto H, Nishide M, Kayano SI. Stabilization of Hydroxy-α-Sanshool by Antioxidants Present in the Genus Zanthoxylum. Foods 2023; 12:3444. [PMID: 37761152 PMCID: PMC10529024 DOI: 10.3390/foods12183444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 09/04/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
Japanese pepper (sansho, Zanthoxylum piperitum) contains several types of sanshools belonging to N-alkylamides. Because of the long-chain unsaturated fatty acids present in their structure, sanshools are prone to oxidative deterioration, which poses problems in processing. In this paper, we evaluated the effects of antioxidants from the genus Zanthoxylum in preventing sanshool degradation using accelerated tests. An ethanolic extract of segment membranes of the sansho fruit pericarp was incubated at 70 °C for 7 days with different antioxidants to determine the residual amount of hydroxy-α-sanshool (HαS) in the extract. α-Tocopherol (α-Toc) showed excellent HαS-stabilizing activity at low concentrations. Among phenolic acids, we noted that the HαS-stabilizing activity increased with the number of hydroxy groups per molecule. For example, gallic acid and its derivatives exhibited excellent sanshool-stabilizing activity. Quercetin was found to be a superior HαS stabilizer compared with hesperetin and naringenin. However, the effective concentration was much higher for phenolic compounds than for α-Toc. These substances are believed to play a role in preventing the decomposition of sanshools in the pericarp of sansho. These sanshool stabilizers should be useful in the development of new beverages, foods, cosmetics, and pharmaceuticals that take advantage of the taste and flavor of sansho.
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Affiliation(s)
- Takahiko Mitani
- Center of Regional Revitalization, Research Center for Food and Agriculture, Wakayama University, Wakayama 640-8510, Japan
| | - Yasuko Yawata
- Center of Regional Revitalization, Research Center for Food and Agriculture, Wakayama University, Wakayama 640-8510, Japan
| | - Nami Yamamoto
- Faculty of Education, Wakayama University, Wakayama 640-8510, Japan;
| | - Yoshiharu Okuno
- Department of Material Science, Wakayama National College of Technology, Gobo 644-0023, Japan;
| | - Hidefumi Sakamoto
- Faculty of Systems Engineering, Wakayama University, Wakayama 640-8510, Japan;
| | - Mitsunori Nishide
- Division of Food and Nutrition, Wakayama Shin-Ai Women’s Junior College, Wakayama 640-0341, Japan;
| | - Shin-ichi Kayano
- Department of Nutrition, Faculty of Health Science, Kio University, Koryo-cho, Nara 635-0832, Japan;
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Suzuki K, Takehara Y, Sakata M, Kawate M, Ohishi N, Sugiyama K, Akai T, Suzuki Y, Sugiyama M, Kawamura T, Morita Y, Kikuchi H, Hiramatsu Y, Yamamoto M, Nasu H, Johnson K, Wieben O, Kurachi K, Takeuchi H. Daikenchuto increases blood flow in the superior mesenteric artery in humans: A comparison study between four-dimensional phase-contrast vastly undersampled isotropic projection reconstruction magnetic resonance imaging and Doppler ultrasound. PLoS One 2021; 16:e0245878. [PMID: 33503053 PMCID: PMC7840032 DOI: 10.1371/journal.pone.0245878] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 01/07/2021] [Indexed: 11/18/2022] Open
Abstract
Respiratory-gated four-dimensional phase-contrast vastly undersampled isotropic projection reconstruction (4D PC-VIPR) is magnetic resonance (MR) imaging technique that enables analysis of vascular morphology and hemodynamics in a single examination using cardiac phase resolved 3D phase-contrast magnetic resonance imaging. The present study aimed to assess the usefulness of 4D PC-VIPR for the superior mesenteric artery (SMA) flowmetry before and after flow increase was induced by the herbal medicine Daikenchuto (TJ-100) by comparing it with Doppler ultrasound (DUS) as a current standard. Twenty healthy volunteers were enrolled in this prospective single-arm study. The peak cross-sectionally averaged velocity was measured by 4D PC-VIPR, peak velocity was measured by DUS, and flow volume (FV) of SMA and aorta were measured by 4D PC-VIPR and DUS 25 min before and after the peroral administration of TJ-100. The peak cross-sectionally averaged velocity, peak velocity, and FV of SMA measured by 4D PC-VIPR and DUS significantly increased after administration of TJ-100 (4D PC-VIPR: the peak cross-sectionally averaged velocity; p = 0.004, FV; p = 0.035, DUS: the peak velocity; p = 0.003, FV; p = 0.010). Furthermore, 4D PC-VIPR can analyze multiple blood vessels simultaneously. The ratio of the SMA FV to the aorta, before and after oral administration on the 4D PC-VIPR test also increased (p = 0.015). The rate of change assessed by 4D PC-VIPR and DUS were significantly correlated (the peak cross-sectionally averaged velocity and peak velocity: r = 0.650; p = 0.005, FV: r = 0.659; p = 0.004). Retrospective 4D PC-VIPR was a useful modality for morphological and hemodynamic analysis of SMA.
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Affiliation(s)
- Katsunori Suzuki
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Yasuo Takehara
- Department of Fundamental Development for Advanced Low Invasive Diagnostic Imaging, Nagoya University, Graduate School of Medicine, Nagoya, Aichi, Japan
| | - Mayu Sakata
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Masanori Kawate
- Department of Radiology, Hamamatsu University Hospital, Hamamatsu, Shizuoka, Japan
| | - Naoki Ohishi
- Department of Radiology, Hamamatsu University Hospital, Hamamatsu, Shizuoka, Japan
| | - Kosuke Sugiyama
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Toshiya Akai
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Yuhi Suzuki
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Masataka Sugiyama
- Department of Fundamental Development for Advanced Low Invasive Diagnostic Imaging, Nagoya University, Graduate School of Medicine, Nagoya, Aichi, Japan
| | - Takafumi Kawamura
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Yoshifumi Morita
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Hirotoshi Kikuchi
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Yoshihiro Hiramatsu
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Masayoshi Yamamoto
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Hatsuko Nasu
- Department of Diagnostic Radiology & Nuclear Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Kevin Johnson
- Department of Medical Physics, University of Wisconsin, Madison, WI, United States of America
- Department of Radiology, University of Wisconsin, Madison, WI, United States of America
| | - Oliver Wieben
- Department of Medical Physics, University of Wisconsin, Madison, WI, United States of America
- Department of Radiology, University of Wisconsin, Madison, WI, United States of America
| | - Kiyotaka Kurachi
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
- * E-mail:
| | - Hiroya Takeuchi
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
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Ohbe H, Jo T, Matsui H, Fushimi K, Yasunaga H. Effect of Daikenchuto for Mechanically Ventilated Patients With Enteral Feeding Intolerance: A Propensity Score-Matched Analysis Using a Nationwide Administrative Inpatient Database. JPEN J Parenter Enteral Nutr 2021; 45:1703-1713. [PMID: 33483948 DOI: 10.1002/jpen.2076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Daikenchuto, a Japanese herbal Kampo medicine, is used to improve gastrointestinal motility in critically ill patients with enteral feeding intolerance (EFI) in Japan. The present study aimed to investigate the effect of Daikenchuto for critically ill patients with EFI. METHODS Using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2018, we identified mechanically ventilated patients in intensive care units (ICUs) who had EFI during mechanical ventilation. We defined EFI as receipt of intravenous metoclopramide during mechanical ventilation. Patients who started Daikenchuto within 2 days of EFI onset were defined as the Daikenchuto group, and the remaining patients were defined as the control group. Propensity score-matched analyses were performed to compare the outcomes between the 2 groups. RESULTS A total of 61,454 patients were included. Of these, 8842 patients (14%) were in the Daikenchuto group. One-to-one propensity score matching created 8701 matched pairs. After propensity score matching, the total number of days receiving enteral nutrition within 28 days of EFI onset was significantly longer in the Daikenchuto group than in the control group (risk difference, 0.9 days; 95% CI, 0.5-1.3 days). There were no significant differences in 28-day in-hospital mortality, hospital-acquired pneumonia, ventilator-free days, length of ICU stay, time to discharge alive, and adverse complications. CONCLUSION This nationwide observational study suggested that use of Daikenchuto may increase the total number of days receiving enteral nutrition in mechanically ventilated patients with EFI.
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Affiliation(s)
- Hiroyuki Ohbe
- Department of Clinical Epidemiology and Health Economics, School of Public Health, University of Tokyo, Tokyo, Japan
| | - Taisuke Jo
- Department of Health Services Research, School of Public Health, University of Tokyo, Tokyo, Japan
| | - Hiroki Matsui
- Department of Clinical Epidemiology and Health Economics, School of Public Health, University of Tokyo, Tokyo, Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan
| | - Hideo Yasunaga
- Department of Clinical Epidemiology and Health Economics, School of Public Health, University of Tokyo, Tokyo, Japan
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Takayama S, Tomita N, Arita R, Ono R, Kikuchi A, Ishii T. Kampo Medicine for Various Aging-Related Symptoms: A Review of Geriatric Syndrome. Front Nutr 2020; 7:86. [PMID: 32766269 PMCID: PMC7381143 DOI: 10.3389/fnut.2020.00086] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Accepted: 05/12/2020] [Indexed: 12/12/2022] Open
Abstract
With the continued growth of the aging population in Japan, geriatric syndrome (GS), which is associated with aging-related symptoms, has become a social problem. GS is caused by physiological and pathological aging and may manifest various symptoms. Physicians use multidisciplinary approaches to provide treatment for individual GS symptoms. Kampo medicine, a Japanese traditional medicine that uses multiple pharmacologically active substances, is useful for many syndromes, conditions, disorders, and diseases associated with GS. Evidence of the effectiveness of Kampo medicine for GS has accumulated in recent years. The effects of Kampo treatment for symptoms related to functional decline of the cardiovascular, respiratory, and digestive systems, cognitive impairment and related disorders, pain and other sensory issues, among others, support the use of Kampo medicine for the management of GS. The role of Kampo medicine for GS is summarized in this review.
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Affiliation(s)
- Shin Takayama
- Department of Kampo and Integrative Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.,Department of Education and Support for Regional Medicine, Tohoku University Hospital, Sendai, Japan.,Department of Kampo Medicine, Tohoku University Hospital, Sendai, Japan
| | - Naoki Tomita
- Department of Geriatrics and Gerontology, Institue of Development, Aging and Cancer, Tohoku University, Sendai, Japan
| | - Ryutaro Arita
- Department of Education and Support for Regional Medicine, Tohoku University Hospital, Sendai, Japan.,Department of Kampo Medicine, Tohoku University Hospital, Sendai, Japan
| | - Rie Ono
- Department of Education and Support for Regional Medicine, Tohoku University Hospital, Sendai, Japan.,Department of Kampo Medicine, Tohoku University Hospital, Sendai, Japan
| | - Akiko Kikuchi
- Department of Kampo and Integrative Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.,Department of Education and Support for Regional Medicine, Tohoku University Hospital, Sendai, Japan.,Department of Kampo Medicine, Tohoku University Hospital, Sendai, Japan
| | - Tadashi Ishii
- Department of Kampo and Integrative Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.,Department of Education and Support for Regional Medicine, Tohoku University Hospital, Sendai, Japan.,Department of Kampo Medicine, Tohoku University Hospital, Sendai, Japan
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7
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Chartier LC, Howarth GS, Mashtoub S. Combined Nutraceuticals: A Novel Approach to Colitis-Associated Colorectal Cancer? Nutr Cancer 2019; 71:199-206. [PMID: 30862196 DOI: 10.1080/01635581.2019.1578391] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 01/07/2019] [Accepted: 01/10/2019] [Indexed: 12/13/2022]
Abstract
Ulcerative colitis is an unremitting and lifelong inflammatory bowel disease that is increasing in prevalence worldwide. Patients display various clinical symptoms such as abdominal pain, diarrhea and fatigue. The etiology of ulcerative colitis remains unknown and the current pharmaceutical treatments are variably effective and not curative, highlighting the need for improved therapeutic approaches. Furthermore, patients with ulcerative colitis are at an increased risk of developing colorectal cancer. Some naturally sourced agents, named nutraceuticals, have been identified to possess anti-inflammatory and antioxidant properties. Of particular interest is Emu Oil, grape seed extract and Japanese Kampo medicine. Previously, Emu Oil has protected and repaired intestinal damage in models of gastrointestinal diseases including colitis and colitis-associated colorectal cancer. Additionally, grape seed extract possesses anticancer properties in vitro. Moreover, Kampo medicine, composed of herbal ingredients, is widely used in Japan for the treatment of various medical conditions and has demonstrated efficacy in targeting cancer cells in vitro. Nutraceuticals in combination have not yet been widely investigated in a setting of colitis-associated colorectal cancer. Investigation into the efficacy of Emu Oil combined with other nutraceuticals, including grape seed extract and Kampo medicine, is warranted as they may provide a novel approach to conventional colitis and colorectal cancer management.
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Affiliation(s)
- Lauren C Chartier
- a Discipline of Physiology, Adelaide Medical School , The University of Adelaide , Adelaide , South Australia
- b Department of Gastroenterology , Women's and Children's Hospital , North Adelaide , South Australia
| | - Gordon S Howarth
- a Discipline of Physiology, Adelaide Medical School , The University of Adelaide , Adelaide , South Australia
- b Department of Gastroenterology , Women's and Children's Hospital , North Adelaide , South Australia
- c School of Animal and Veterinary Sciences , The University of Adelaide , Roseworthy , South Australia
| | - Suzanne Mashtoub
- a Discipline of Physiology, Adelaide Medical School , The University of Adelaide , Adelaide , South Australia
- b Department of Gastroenterology , Women's and Children's Hospital , North Adelaide , South Australia
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Daikenchuto accelerates the recovery from prolonged postoperative ileus after open abdominal surgery: a subgroup analysis of three randomized controlled trials. Surg Today 2019; 49:704-711. [PMID: 30805720 PMCID: PMC6647501 DOI: 10.1007/s00595-019-01787-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 02/07/2019] [Indexed: 12/21/2022]
Abstract
Purpose Prolonged postoperative ileus (POI) is a common complication after open abdominal surgery (OAS). Daikenchuto (DKT), a traditional Japanese medicine that peripherally stimulates the neurogenic pathway, is used to treat prolonged POI in Japan. To analyze whether DKT accelerates the recovery from prolonged POI after OAS, we conducted a secondary analysis of three multicenter randomized controlled trials (RCTs). Methods A secondary analysis of the three RCTs supported by the Japanese Foundation for Multidisciplinary Treatment of Cancer (project numbers 39-0902, 40-1001, 42-1002) assessing the effect of DKT on prolonged POI in patients who had undergone OAS for colon, liver, or gastric cancer was performed. The subgroup included 410 patients with no bowel movement (BM) before the first diet, a DKT group (n = 214), and a placebo group (n = 196). Patients received either 5 g DKT or a placebo orally, three times a day. The primary endpoint was defined as the time from the end of surgery to the first bowel movement (FBM). A sensitivity analysis was also performed on the age, body mass index and dosage as subgroup analyses. Results The primary endpoint was significantly accelerated in the DKT group compared with the placebo group (p = 0.004; hazard ratio 1.337). The median time to the FBM was 113.8 h in the placebo group and 99.1 h in the DKT treatment group. Conclusions The subgroup analysis showed that DKT significantly accelerated the recovery from prolonged POI following OAS. Trial registration number UMIN000026292.
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Kaido T, Shinoda M, Inomata Y, Yagi T, Akamatsu N, Takada Y, Ohdan H, Shimamura T, Ogura Y, Eguchi S, Eguchi H, Ogata S, Yoshizumi T, Ikegami T, Yamamoto M, Morita S, Uemoto S. Effect of herbal medicine daikenchuto on oral and enteral caloric intake after liver transplantation: A multicenter, randomized controlled trial. Nutrition 2018; 54:68-75. [PMID: 29747091 DOI: 10.1016/j.nut.2018.02.022] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 02/12/2018] [Accepted: 02/28/2018] [Indexed: 01/10/2023]
Abstract
OBJECTIVE Postoperative early oral or enteral intake is a crucial element of the Enhanced Recovery After Surgery (ERAS) protocol. However, normal food intake or enteral feeding cannot be started early in the presence of coexisting bowel dysfunction in patients undergoing liver transplantation (LT). The aim of this multicenter, randomized, double-blinded, placebo-controlled trial was to determine the enhancement effects of the Japanese herbal medicine Daikenchuto (DKT) on oral/enteral caloric intake in patients undergoing LT. METHODS A total of 112 adult patients undergoing LT at 14 Japanese centers were enrolled. The patients were randomly assigned to receive either DKT or placebo from postoperative day (POD) 1 to 14. The primary endpoints were total oral/enteral caloric intake, abdominal distension, and pain on POD 7. The secondary endpoints included sequential changes in total oral/enteral caloric intake after LT, and portal venous flow volume and velocity in the graft. RESULTS A total of 104 patients (DKT, n = 55; placebo, n = 49) were included in the analyses. There were no significant differences between the two groups in terms of primary endpoints. However, postoperative total oral/enteral caloric intake was significantly accelerated in the DKT group compared with the placebo group (P = 0.023). Moreover, portal venous flow volume (POD 10, 14) and velocity (POD 14) were significantly higher in the DKT group than in the placebo group (P = 0.047, P = 0.025, P = 0.014, respectively). CONCLUSIONS Postoperative administration of DKT may enhance total oral/enteral caloric intake and portal venous flow volume and velocity after LT and favorably contribute to the performance of the ERAS protocol.
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Affiliation(s)
- Toshimi Kaido
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
| | - Masahiro Shinoda
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Yukihiro Inomata
- Department of Transplantation/Pediatric Surgery, Postgraduate School of Medicine, Kumamoto University, Kumamoto, Japan
| | - Takahito Yagi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Nobuhisa Akamatsu
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Yasutsugu Takada
- Department of Hepato-Pancreatic-Biliary and Breast Surgery, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tsuyoshi Shimamura
- Division of Organ Transplantation, Hokkaido University Hospital, Sapporo, Japan
| | - Yasuhiro Ogura
- Department of Transplantation Surgery, Nagoya University Hospital, Nagoya, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Satoshi Ogata
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toshihiko Ikegami
- First Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Michio Yamamoto
- Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan
| | - Satoshi Morita
- Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Takayama S, Arita R, Kikuchi A, Ohsawa M, Kaneko S, Ishii T. Clinical Practice Guidelines and Evidence for the Efficacy of Traditional Japanese Herbal Medicine (Kampo) in Treating Geriatric Patients. Front Nutr 2018; 5:66. [PMID: 30083536 PMCID: PMC6064728 DOI: 10.3389/fnut.2018.00066] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 07/02/2018] [Indexed: 11/13/2022] Open
Abstract
Frailty is defined as a state of increased vulnerability to poor resolution of homeostasis following stress, which increases the risk of adverse outcomes such as falls, delirium, and disability in the elderly. Recently in Japan, clinical practice guidelines (CPG) have recommended kampo treatment. We conducted a search for reports on Japanese CPG and kampo medicine in the treatment of symptoms in the elderly. The search was performed using the databases PubMed, Ichushi Web, J-Stage, Japan Medical Publishers Association, Medical Information Network Distribution Service, and CPG containing kampo products in Japan; reports from January 1st, 2012 to October 31st, 2017 were reviewed. Over the past 5 years, nine CPGs have recommended kampo treatment based on the evidence for improvement in skin symptoms, cough, gastro-intestinal dysfunction, urinary dysfunction, and dementia. Treatments with kampo medicine are performed depending on the coexistence of manifestations based on the original kampo concept, i.e., cognitive dysfunction and dementia with sarcopenia showing urinary disorder. Each kampo formula includes multiple crude drugs that have several pharmacological functions; these drugs include alkaloids, glycosides, and polysaccharides. Thus, kampo formula has an effect on multiple organs and coordinates the relationship between the brain, endocrine system, immune system, and skeletal muscles. Kampo treatment can be considered as supporting holistic medicine in elderly individuals with frailty.
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Affiliation(s)
- Shin Takayama
- Department of Education and Support for Regional Medicine, Department of Kampo Medicine, Tohoku University Hospital, Sendai, Japan
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11
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Efficacy and Safety of Daikenchuto for Constipation and Dose-Dependent Differences in Clinical Effects. Int J Chronic Dis 2018; 2018:1296717. [PMID: 29693001 PMCID: PMC5859840 DOI: 10.1155/2018/1296717] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Revised: 01/23/2018] [Accepted: 01/31/2018] [Indexed: 12/20/2022] Open
Abstract
Background Daikenchuto (DKT) is a Kampo medicine used for the treatment of constipation. In this study, we evaluated the effectiveness of DKT against constipation. Patients and Methods Thirty-three patients administered DKT for constipation were selected and divided into low-dose (7.5 g DKT; n = 22) and high-dose (15 g DKT; n = 11) groups. We retrospectively evaluated weekly defaecation frequency, side effects, and clinical laboratory data. Results Median defaecation frequencies after DKT administration (5, 5.5, 5, and 8 for the first, second, third, and fourth weeks, resp.) were significantly higher than that before DKT administration (2) in all 33 cases (P < 0.01). One case (3%) of watery stool, one case of loose stools (3%), and no cases of abdominal pain (0%) were observed. Median defaecation frequencies in the high-dose group (7 and 9) were significantly higher than those in the low-dose group (4 and 3) in the first (P = 0.0133) and second (P = 0.0101) weeks, respectively. There was no significant change in clinical laboratory values. Conclusion We suggest that DKT increases defaecation frequency and is safe for treating constipation.
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Inoue A, Furukawa A, Yamamoto H, Ohta S, Linh NDH, Syerikjan T, Kaida S, Yamaguchi T, Murata S, Obata T, Tani M, Murata K. Acceleration of small bowel motility after oral administration of dai-kenchu-to (TJ-100) assessed by cine magnetic resonance imaging. PLoS One 2018; 13:e0191044. [PMID: 29320574 PMCID: PMC5761958 DOI: 10.1371/journal.pone.0191044] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Accepted: 12/27/2017] [Indexed: 12/11/2022] Open
Abstract
Dai-kenchu-to (TJ-100) is an herbal medicine used to shorten the duration of intestinal transit by accelerating intestinal movement. However, intestinal movement in itself has not been evaluated in healthy volunteers using radiography, fluoroscopy, and radioisotopes because of exposure to ionizing radiation. The purpose of this study was to evaluate the effect of TJ-100 on intestinal motility using cinematic magnetic resonance imaging (cine MRI) with a steady-state free precession sequence. Ten healthy male volunteers received 5 g of either TJ-100 or lactose without disclosure of the identity of the substance. Each volunteer underwent two MRI examinations after taking the substances (TJ-100 and lactose) on separate days. They drank 1200 mL of tap water and underwent cine MRI after 10 min. A steady-state free precession sequence was used for imaging, which was performed thrice at 0, 10, 20, 30, 40, and 50 min. The bowel contraction frequency and distention score were assessed. Wilcoxon signed-rank test was used, and differences were considered significant at a P-value <0.05. The bowel contraction frequency tended to be greater in the TJ-100 group and was significantly different in the ileum at 20 (TJ-100, 8.95 ± 2.88; lactose, 4.80 ± 2.92; P < 0.05) and 50 min (TJ-100, 9.45 ± 4.49; lactose, 4.45 ± 2.65; P < 0.05) between the groups. No significant differences were observed in the bowel distention scores. Cine MRI demonstrated that TJ-100 activated intestinal motility without dependence on ileum distention.
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Affiliation(s)
- Akitoshi Inoue
- Department of Radiology, Shiga University of Medical Science, Otsu, Shiga, Japan
- * E-mail:
| | - Akira Furukawa
- Department of Radiological Science, Tokyo Metropolitan University, Arakawa, Tokyo, Japan
| | - Hiroshi Yamamoto
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan
| | - Shinichi Ohta
- Department of Radiology, Shiga University of Medical Science, Otsu, Shiga, Japan
| | - Nguyen Dai Hung Linh
- Department of Radiological Science, Tokyo Metropolitan University, Arakawa, Tokyo, Japan
| | - Tulyeubai Syerikjan
- Department of Radiological Science, Tokyo Metropolitan University, Arakawa, Tokyo, Japan
| | - Sachiko Kaida
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan
| | - Tsuyoshi Yamaguchi
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan
| | - Satoshi Murata
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan
| | - Toru Obata
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan
| | - Masaji Tani
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan
| | - Kiyoshi Murata
- Department of Radiology, Shiga University of Medical Science, Otsu, Shiga, Japan
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Nishino T, Yoshida T, Goto M, Inoue S, Minato T, Fujiwara S, Yamamoto Y, Furukita Y, Yuasa Y, Yamai H, Takechi H, Toba H, Takizawa H, Yoshida M, Seike J, Miyoshi T, Tangoku A. The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial. Esophagus 2018; 15:75-82. [PMID: 29892933 PMCID: PMC5884909 DOI: 10.1007/s10388-017-0601-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Accepted: 12/11/2017] [Indexed: 02/03/2023]
Abstract
BACKGROUND Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. METHODS Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. RESULTS We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. CONCLUSIONS TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.
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Affiliation(s)
- Takeshi Nishino
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
| | - Takahiro Yoshida
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Masakazu Goto
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Seiya Inoue
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Takuya Minato
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Satoshi Fujiwara
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Yota Yamamoto
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Yoshihito Furukita
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Yasuhiro Yuasa
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Hiromichi Yamai
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Hirokazu Takechi
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Hiroaki Toba
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Hiromitsu Takizawa
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Mitsuteru Yoshida
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Junichi Seike
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Takanori Miyoshi
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Akira Tangoku
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
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Takayama S, Kaneko S, Numata T, Kamiya T, Arita R, Saito N, Kikuchi A, Ohsawa M, Kohayagawa Y, Ishii T. Literature Review: Herbal Medicine Treatment after Large-Scale Disasters. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2017; 45:1345-1364. [DOI: 10.1142/s0192415x17500744] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Large-scale natural disasters, such as earthquakes, tsunamis, volcanic eruptions, and typhoons, occur worldwide. After the Great East Japan earthquake and tsunami, our medical support operation’s experiences suggested that traditional medicine might be useful for treating the various symptoms of the survivors. However, little information is available regarding herbal medicine treatment in such situations. Considering that further disasters will occur, we performed a literature review and summarized the traditional medicine approaches for treatment after large-scale disasters. We searched PubMed and Cochrane Library for articles written in English, and Ichushi for those written in Japanese. Articles published before 31 March 2016 were included. Keywords “disaster” and “herbal medicine” were used in our search. Among studies involving herbal medicine after a disaster, we found two randomized controlled trials investigating post-traumatic stress disorder (PTSD), three retrospective investigations of trauma or common diseases, and seven case series or case reports of dizziness, pain, and psychosomatic symptoms. In conclusion, herbal medicine has been used to treat trauma, PTSD, and other symptoms after disasters. However, few articles have been published, likely due to the difficulty in designing high quality studies in such situations. Further study will be needed to clarify the usefulness of herbal medicine after disasters.
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Affiliation(s)
- Shin Takayama
- Department of Education and Support for Regional Medicine, Department of Kampo Medicine, Tohoku University Hospital, 1-1, Seiryomachi, Aobaku, Sendai City, Miyagi Prefecture 980-8574, Japan
| | - Soichiro Kaneko
- Department of Education and Support for Regional Medicine, Department of Kampo Medicine, Tohoku University Hospital, 1-1, Seiryomachi, Aobaku, Sendai City, Miyagi Prefecture 980-8574, Japan
| | - Takehiro Numata
- Department of Education and Support for Regional Medicine, Department of Kampo Medicine, Tohoku University Hospital, 1-1, Seiryomachi, Aobaku, Sendai City, Miyagi Prefecture 980-8574, Japan
| | - Tetsuharu Kamiya
- Department of Education and Support for Regional Medicine, Department of Kampo Medicine, Tohoku University Hospital, 1-1, Seiryomachi, Aobaku, Sendai City, Miyagi Prefecture 980-8574, Japan
| | - Ryutaro Arita
- Department of Education and Support for Regional Medicine, Department of Kampo Medicine, Tohoku University Hospital, 1-1, Seiryomachi, Aobaku, Sendai City, Miyagi Prefecture 980-8574, Japan
| | - Natsumi Saito
- Department of Education and Support for Regional Medicine, Department of Kampo Medicine, Tohoku University Hospital, 1-1, Seiryomachi, Aobaku, Sendai City, Miyagi Prefecture 980-8574, Japan
| | - Akiko Kikuchi
- Department of Education and Support for Regional Medicine, Department of Kampo Medicine, Tohoku University Hospital, 1-1, Seiryomachi, Aobaku, Sendai City, Miyagi Prefecture 980-8574, Japan
| | - Minoru Ohsawa
- Department of Education and Support for Regional Medicine, Department of Kampo Medicine, Tohoku University Hospital, 1-1, Seiryomachi, Aobaku, Sendai City, Miyagi Prefecture 980-8574, Japan
| | - Yoshitaka Kohayagawa
- National Disaster Medical Center, 8-15 Oota-machi, Fukushima Prefecture 960-8068, Japan
| | - Tadashi Ishii
- Department of Education and Support for Regional Medicine, Department of Kampo Medicine, Tohoku University Hospital, 1-1, Seiryomachi, Aobaku, Sendai City, Miyagi Prefecture 980-8574, Japan
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Nagata T, Toume K, Long LX, Hirano K, Watanabe T, Sekine S, Okumura T, Komatsu K, Tsukada K. Anticancer effect of a Kampo preparation Daikenchuto. J Nat Med 2016; 70:627-33. [PMID: 27059786 DOI: 10.1007/s11418-016-0989-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2015] [Accepted: 03/23/2016] [Indexed: 10/22/2022]
Abstract
No traditional Japanese and Chinese herbal preparations have been shown to be effective antitumor agents, and a Japanese herbal therapy (Kampo medicine) for cancer that causes fewer adverse drug reactions than orthodox pharmaceuticals is desired. Our present study demonstrated that a Kampo preparation Daikenchuto (DKT) exerts an antitumor effect against various cancer cells. We also discovered an antitumor factor in Japanese Zanthoxylum peel, which is an ingredient of DKT. Breast, esophageal, gastric, and colon cancer cell lines were individually incubated with DKT for 1-72 h, followed by assessment of tumor growth inhibition by MTT assay. The cancer cells were also analyzed for apoptotic changes after DKT treatment. Nude mice were used to establish a model of gastric cancer tumor growth and peritoneal disseminated metastasis, in which the number of peritoneal disseminations was evaluated after oral administration of DKT for 4 weeks. In addition, the antitumor effects of the individual DKT ingredients (viz., ginseng, Japanese Zanthoxylum peel, and processed ginger) and other Kampo preparations were also analyzed. The antitumor effect of DKT was demonstrated in gastric, breast, esophageal, and colon cancer cells. DKT treatment induced apoptosis in these cells. Oral administration of DKT had a tendency to reduce the growth and significantly reduced the peritoneal dissemination of gastric cancer in the nude mouse model compared with control. DKT exhibited a higher antitumor effect than other Kampo preparations. Furthermore, Japanese Zanthoxylum peel, an ingredient of DKT, showed a particularly potent antitumor effect. Our study indicated that DKT is useful as a Kampo preparation for cancer therapy. We also showed that Japanese Zanthoxylum peel, an ingredient of DKT, contains an antitumor factor.
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Affiliation(s)
- Takuya Nagata
- Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.
| | - Kazufumi Toume
- Division of Pharmacognosy, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, Japan
| | - Lv Xiao Long
- Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan
| | - Katsuhisa Hirano
- Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan
| | - Toru Watanabe
- Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan
| | - Shinichi Sekine
- Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan
| | - Tomoyuki Okumura
- Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan
| | - Katsuko Komatsu
- Division of Pharmacognosy, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, Japan
| | - Kazuhiro Tsukada
- Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan
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16
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Japanese Guidelines for Nutrition Support Therapy in the Adult and Pediatric Critically Ill Patients. ACTA ACUST UNITED AC 2016. [DOI: 10.3918/jsicm.23.185] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Anti-Inflammatory Effect of the Kampo Japanese Traditional Medicine daikenchuto After Colorectal Resection. Int Surg 2015. [DOI: 10.9738/intsurg-d-14-00280.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Here we analyzed whether Daikenchuto (DKT) suppresses postoperative inflammatory reactions in patients who have undergone elective colorectal surgery. DKT is one of the most frequently prescribed traditional (Kampo) medicines in Japan. DKT is reported to have various beneficial effects on bowel disorders. It was recently reported that DKT also has an anti-inflammatory effect. Consecutive patients with colorectal cancer who underwent elective colorectal resection were separated into two groups. A total of 67 patients began a DKT regimen after surgery (DKT group) and 53 patients did not begin the DKT regimen after surgery (control group). We observed a steady postsurgery increase in the white blood cell (WBC) count of all patients on postoperative day 1 (POD 1), whereas the WBC count decreased at PODs 3 and 7. When we compared the WBC values of the DKT group (6147.2 ± 2217.3 per microliter) and control (7071.1 ± 2828.0 per microliter) groups on POD 7, we found significant differences (P = 0.038). There was no significant side effect due to DKT, except for one case of mildly impaired liver function. Our results suggest that DKT administration may have an anti-inflammatory effect during the postoperative period. Further studies are warranted to investigate the possibility of using DKT as a therapeutic agent based on its anti-inflammatory effect.
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Kono T, Shimada M, Yamamoto M, Kaneko A, Oomiya Y, Kubota K, Kase Y, Lee K, Uezono Y. Complementary and synergistic therapeutic effects of compounds found in Kampo medicine: analysis of daikenchuto. Front Pharmacol 2015; 6:159. [PMID: 26300774 PMCID: PMC4523940 DOI: 10.3389/fphar.2015.00159] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Accepted: 07/17/2015] [Indexed: 01/17/2023] Open
Abstract
Herbal medicines have been used in Japan for more than 1500 years and traditional Japanese medicines (Kampo medicines) are now fully integrated into the modern healthcare system. In total, 148 Kampo formulae are officially approved as prescription drugs and covered by the national health insurance system in Japan. However, despite their long track record of clinical use, the multi-targeted, multi-component properties of Kampo medicines, which are fundamentally different from Western medicines, have made it difficult to create a suitable framework for conducting well-designed, large-scale clinical trials. In turn, this has led to misconceptions among western trained physicians concerning the paucity of scientific evidence for the beneficial effects of Kampo medicines. Fortunately, there has been a recent surge in scientifically robust data from basic and clinical studies for some of the Kampo medicines, e.g., daikenchuto (TU-100). Numerous basic and clinical studies on TU-100, including placebo-controlled double-blind studies for various gastrointestinal disorders, and absorption, distribution, metabolism and excretion (ADME) studies, have been conducted or are in the process of being conducted in both Japan and the USA. Clinical studies suggest that TU-100 is beneficial for postoperative complications, especially ileus and abdominal bloating. ADME and basic studies indicate that the effect of TU-100 is a composite of numerous actions mediated by multiple compounds supplied via multiple routes. In addition to known mechanisms of action via enteric/sensory nerve stimulation, novel mechanisms via the TRPA1 channel and two pore domain potassium channels have recently been elucidated. TU-100 compounds target these channels with and without absorption, both before and after metabolic activation by enteric flora, with different timings and possibly with synergism.
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Affiliation(s)
- Toru Kono
- Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital Sapporo, Hokkaido, Japan ; Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University Sapporo, Japan ; Department of Surgery, Institute of Health Biosciences, Graduate School of Medicine, Tokushima University Tokushima, Japan
| | - Mitsuo Shimada
- Department of Surgery, Institute of Health Biosciences, Graduate School of Medicine, Tokushima University Tokushima, Japan
| | - Masahiro Yamamoto
- Kampo Scientific Strategies Division, Tsumura Research Laboratories, Tsumura & CO. Ami, Japan
| | - Atushi Kaneko
- Kampo Scientific Strategies Division, Tsumura Research Laboratories, Tsumura & CO. Ami, Japan
| | - Yuji Oomiya
- Kampo Scientific Strategies Division, Tsumura Research Laboratories, Tsumura & CO. Ami, Japan
| | - Kunitsugu Kubota
- Kampo Scientific Strategies Division, Tsumura Research Laboratories, Tsumura & CO. Ami, Japan
| | - Yoshio Kase
- Kampo Scientific Strategies Division, Tsumura Research Laboratories, Tsumura & CO. Ami, Japan
| | - Keiko Lee
- Kampo Scientific Strategies Division, International Pharmaceutical Development Department, Tsumura & CO. Tokyo, Japan
| | - Yasuhito Uezono
- Division of Cancer Pathophysiology, National Cancer Center Research Institute Tokyo, Japan
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Yoshikawa K, Shimada M, Wakabayashi G, Ishida K, Kaiho T, Kitagawa Y, Sakamoto J, Shiraishi N, Koeda K, Mochiki E, Saikawa Y, Yamaguchi K, Watanabe M, Morita S, Kitano S, Saji S, Kanematsu T, Kitajima M. Effect of Daikenchuto, a Traditional Japanese Herbal Medicine, after Total Gastrectomy for Gastric Cancer: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase II Trial. J Am Coll Surg 2015; 221:571-8. [DOI: 10.1016/j.jamcollsurg.2015.03.004] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2015] [Revised: 02/28/2015] [Accepted: 03/09/2015] [Indexed: 11/24/2022]
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20
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Katsuno H, Maeda K, Kaiho T, Kunieda K, Funahashi K, Sakamoto J, Kono T, Hasegawa H, Furukawa Y, Imazu Y, Morita S, Watanabe M. Clinical efficacy of Daikenchuto for gastrointestinal dysfunction following colon surgery: a randomized, double-blind, multicenter, placebo-controlled study (JFMC39-0902). Jpn J Clin Oncol 2015; 45:650-6. [PMID: 25972515 PMCID: PMC4485603 DOI: 10.1093/jjco/hyv056] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Accepted: 03/24/2015] [Indexed: 12/20/2022] Open
Abstract
Objective This exploratory trial was performed to determine whether Daikenchuto accelerates recovery of gastrointestinal function in patients undergoing open colectomy for colon cancer. Methods A total of 386 patients undergoing colectomy at 1 of the 51 clinical trial sites in Japan from January 2009 to June 2011 were registered for the study (JFMC39-0902). Patients received either placebo or Daikenchuto (15.0 g/day, t.i.d) between post-operative day 2 and post-operative day 8. Primary end-points included time to first bowel movement, frequency of bowel movement and stool form. The incidence of intestinal obstruction was evaluated post-operatively. The safety profile of Daikenchuto until post-operative day 8 was also evaluated. Results The results for 336 patients (Daikenchuto, n = 174; placebo, n = 162) were available for statistical analysis. The time to first bowel movement did not differ significantly between the two groups. All patients reported having diarrhea or soft stools immediately after surgery, and the time until stool normalization (50th percentile) in the Daikenchuto and placebo groups was 6 days and 7 days, respectively. The placebo group had a significantly greater number of hard stools at post-operative day 8 (P = 0.016), and bowel movement frequency continued to increase until post-operative day 8 as well. In contrast, bowel movement frequency in the Daikenchuto group increased until post-operative day 6, however decreased from post-operative day 7 and was significantly lower at post-operative day 8 compared with the placebo group (P = 0.024). Conclusion The moderate effects of Daikenchuto were observed ∼1 week after the operation. Although Daikenchuto had an effect on gastrointestinal function after open surgery in patients with colon cancer, this study did not show its clinical benefits adequately.
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Affiliation(s)
- Hidetoshi Katsuno
- Department of Surgery, Fujita Health University, School of Medicine, Toyoake
| | - Koutarou Maeda
- Department of Surgery, Fujita Health University, School of Medicine, Toyoake
| | - Takashi Kaiho
- Department of Surgery, Kimitsu Chuo Hospital, Kisarazu
| | - Katsuyuki Kunieda
- Department of Surgery, Gifu Prefectural General Medical Center, Gifu
| | - Kimihiko Funahashi
- Department of General and Gastroenterological Surgery, Toho University Omori Medical Center, Tokyo
| | | | - Toru Kono
- Advanced Surgery Center, Sapporo Higashi Tokushukai Hospital, Sapporo
| | | | | | | | - Satoshi Morita
- Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto
| | - Masahiko Watanabe
- Department of Surgery, Kitasato University School of Medicine, Sagamihara, Japan
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Abstract
Constipation is characterized by a variety of bowel symptoms such as difficulty passing stool, hard stool, and a feeling of incomplete evacuation. The multifactorial causes of constipation limit the clinical efficacy of current conventional treatments that use a single drug that acts through only one pathway. To complement the shortcomings of the current Western medical model and provide a complete holistic approach, herbal medicines capable of targeting multiple organs and cellular sites may be used. In Japan, many herbs and herbal combinations have traditionally been used as foods and medicines. Currently, Japanese physicians use standardized herbal combinations that provide consistent and essential quality and quantity. This review highlights representative Japanese herbal medicines (JHMs), Rhei rhizoma-based JHMs including Daiokanzoto and Mashiningan, and Kenchuto-based JHMs including Keishikashakuyakuto and Daikenchuto, which coordinate the motility of the alimentary tract. This review provides a framework to better understand the clinical and pharmacological efficacies of JHMs on constipation according to the unique theory of Japanese traditional medicine, known as Kampo medicine.
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Affiliation(s)
- Norio Iizuka
- Department of Kampo Medicine, Yamaguchi University Hospital , Ube, Japan
| | - Yoshihiko Hamamoto
- Department of Computer Science and Systems Engineering, Faculty of Engineering, Yamaguchi University , Ube, Japan
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Traditional Japanese medicine daikenchuto improves functional constipation in poststroke patients. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2014; 2014:231258. [PMID: 25089144 PMCID: PMC4095989 DOI: 10.1155/2014/231258] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Revised: 05/05/2014] [Accepted: 05/13/2014] [Indexed: 12/18/2022]
Abstract
Poststroke patients with functional constipation, assessed by the Rome III criteria, from 6 hospitals were recruited in a study on the effects of the traditional Japanese medicine Daikenchuto (DKT) on constipation. Thirty-four patients (17 men and 17 women; mean age: 78.1 ± 11.6 years) were randomly assigned to 2 groups; all patients received conventional therapy for constipation, and patients in the DKT group received 15 g/day of DKT for 4 weeks. Constipation scoring system (CSS) points and the gas volume score (GVS) (the measure of the intestinal gas volume calculated from plain abdominal radiographs) were recorded before and after a 4-week observation period. The total score on the CSS improved significantly in the DKT group compared to the control (P < 0.01). In addition, scores for some CSS subcategories (frequency of bowel movements, feeling of incomplete evacuation, and need for enema/disimpaction) significantly improved in the DKT group (P < 0.01, P = 0.049, and P = 0.03, resp.). The GVS was also significantly reduced in the DKT group compared to the control (P = 0.03). DKT in addition to conventional therapy is effective in treating functional constipation in poststroke patients. This study was a randomized controlled trial and was registered in the UMIN Clinical Trial Registry (no. UMIN000007393).
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Sato Y. [Improvement effect of Daikenchuto on morphine-induced constipation through gastrointestinal peptides]. Nihon Yakurigaku Zasshi 2014; 143:120-5. [PMID: 24614634 DOI: 10.1254/fpj.143.120] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Effect of TU-100, a traditional Japanese medicine, administered after hepatic resection in patients with liver cancer: a multi-center, phase III trial (JFMC40-1001). Int J Clin Oncol 2014; 20:95-104. [PMID: 24595550 DOI: 10.1007/s10147-014-0678-2] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2013] [Accepted: 02/06/2014] [Indexed: 01/26/2023]
Abstract
BACKGROUND This multi-center, phase III trial assesses the efficacy of daikenchuto (TU-100) on gastrointestinal disorders after hepatic resection (UMIN Registration No. 000003103). MATERIALS AND METHODS A total of 231 patients, who underwent hepatic resection at 26 Japanese centers, were enrolled. Patients were randomly assigned to receive either oral doses (15 g/day, three times a day) of TU-100 or placebo control from preoperative day 3 to postoperative day 10, except on the day of surgery. Primary end points were the time from extubation until the first postoperative bowel movement (FBM-T), serum C-reactive protein (CRP) and ammonia levels. RESULTS Finally, 209 patients (TU-100: n = 108, placebo: n = 101) were included in the statistical analysis. The median FBM-T was 88.2 h (95 % CI 74.0-94.1) in the TU-100 group and 93.1 h (95 % CI 83.3-99.4) in the placebo group, demonstrating that TU-100 accelerated the time to first bowel movement significantly more than placebo control. Serum CRP levels did not differ significantly during the study period, although serum CRP levels in the TU-100 group tended to be lower than those in the placebo group in patients with grade B liver damage. Meanwhile, the two groups had similar serum ammonia levels. TU-100-related serious adverse events did not occur during the study. CONCLUSIONS TU-100 appears to improve gastrointestinal dysmotility and reduce serum CRP levels in patients with grade B liver damage after hepatectomy. TU-100 is an effective treatment option after hepatic resection in patients with liver cancer.
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Endo M, Hori M, Ozaki H, Oikawa T, Hanawa T. Daikenchuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus by anti-inflammatory action through nicotinic acetylcholine receptors. J Gastroenterol 2014; 49:1026-39. [PMID: 23846546 PMCID: PMC4048467 DOI: 10.1007/s00535-013-0854-6] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2013] [Accepted: 06/15/2013] [Indexed: 02/04/2023]
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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Affiliation(s)
- Mari Endo
- Department of Clinical Research, Oriental Medicine Research Center, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642 Japan
| | - Masatoshi Hori
- Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657 Japan
| | - Hiroshi Ozaki
- Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657 Japan
| | - Tetsuro Oikawa
- Department of Clinical Research, Oriental Medicine Research Center, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642 Japan
| | - Toshihiko Hanawa
- Department of Clinical Research, Oriental Medicine Research Center, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642 Japan ,Department of Oriental Medicine, Doctoral Program of Medical Science, Kitasato University Graduate School, 1-15-1 kitasato, Sagamihara-shi, Kanagawa, 228-8555 Japan
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Park HJ, Kim DH, Park SJ, Kim JM, Ryu JH. Ginseng in traditional herbal prescriptions. J Ginseng Res 2013; 36:225-41. [PMID: 23717123 PMCID: PMC3659587 DOI: 10.5142/jgr.2012.36.3.225] [Citation(s) in RCA: 123] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2011] [Revised: 03/20/2012] [Accepted: 03/20/2012] [Indexed: 01/30/2023] Open
Abstract
Panax ginseng Meyer has been widely used as a tonic in traditional Korean, Chinese, and Japanese herbal medicines and in Western herbal preparations for thousands of years. In the past, ginseng was very rare and was considered to have mysterious powers. Today, the efficacy of drugs must be tested through well-designed clinical trials or meta-analyses, and ginseng is no exception. In the present review, we discuss the functions of ginseng described in historical documents and describe how these functions are taken into account in herbal prescriptions. We also discuss the findings of experimental pharmacological research on the functions of ginseng in ginseng-containing prescriptions and how these prescriptions have been applied in modern therapeutic interventions. The present review on the functions of ginseng in traditional prescriptions helps to demystify ginseng and, as a result, may contribute to expanding the use of ginseng or ginseng-containing prescriptions.
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Affiliation(s)
- Ho Jae Park
- Department of Oriental Pharmaceutical Science, Kyung Hee University, Seoul 130-701, Korea
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Kampo medicines for gastrointestinal tract disorders: a review of basic science and clinical evidence and their future application. J Gastroenterol 2013; 48:452-62. [PMID: 23503839 PMCID: PMC3698434 DOI: 10.1007/s00535-013-0788-z] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2013] [Accepted: 02/20/2013] [Indexed: 02/04/2023]
Abstract
Treatment with kampo, the Japanese traditional medicine, is a form of pharmacological therapy that combines modern Western and traditional Asian medical practices. In Japan, various traditional medicines are often combined with Western medicines and prescribed for patients with diseases such as gastroesophageal reflux disease, functional dyspepsia, chronic gastritis, irritable bowel syndrome, and post-operative ileus. Based on numerous past observations, Japanese traditional medicines are thought to be particularly useful in the treatment of medically unexplained physical symptoms such as nausea, abdominal discomfort, and anorexia. However, the detailed mechanism by which they mediate their pharmacological action is yet unknown. In addition, the clinical evidence to support their use is insufficient. This review focuses on the basic evidence of the pharmacological action and the clinical efficacies of kampo medicines accumulated over several past decades. In addition, we introduce both the current novel insights into kampo medicines and the therapeutic approach employed when they are used to treat various disorders of the gastrointestinal tract.
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Effect of the Japanese herbal kampo medicine dai-kenchu-to on postoperative adhesive small bowel obstruction requiring long-tube decompression: a propensity score analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2011; 2011:264289. [PMID: 21584269 PMCID: PMC3092181 DOI: 10.1155/2011/264289] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2010] [Accepted: 01/24/2011] [Indexed: 01/31/2023]
Abstract
Adhesive small bowel obstruction (ASBO) is an adverse consequence of abdominal surgery. Although the Kampo medicine Dai-kenchu-to is widely used in Japan for treatment of postoperative ASBO, rigorous clinical studies for its use have not been performed. In the present retrospective observational study using the Japanese diagnosis procedure combination inpatient database, we selected 288 propensity-score-matched patients with early postoperative ASBO following colorectal cancer surgery, who received long-tube decompression (LTD) with or without Dai-kenchu-to administration. The success rates of LTD were not significantly different between Dai-kenchu-to users and nonusers (84.7% versus 78.5%; P = .224), while Dai-kenchu-to users showed a shorter duration of LTD (8 versus 10 days; P = .012), shorter duration between long-tube insertion and discharge (23 versus 25 days; P = .018), and lower hospital charges ($23,086 versus $26,950; P = .018) compared with Dai-kenchu-to nonusers. In conclusion, the present study suggests that Dai-kenchu-to is effective for reducing the duration of LTD and saving costs.
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Kono T. [Kampo medicine daikenchuto--Its Exodus from the complementary and alternative medicines]. Nihon Yakurigaku Zasshi 2011; 137:13-17. [PMID: 21233583 DOI: 10.1254/fpj.137.13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
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Inoue K, Naito Y, Takagi T, Hayashi N, Hirai Y, Mizushima K, Horie R, Fukumoto K, Yamada S, Harusato A, Hirata I, Omatsu T, Yoshida N, Uchiyama K, Ishikawa T, Handa O, Konishi H, Wakabayashi N, Yagi N, Ichikawa H, Kokura S, Yoshikawa T. Daikenchuto, a Kampo medicine, regulates intestinal fibrosis associated with decreasing expression of heat shock protein 47 and collagen content in a rat colitis model. Biol Pharm Bull 2011; 34:1659-1665. [PMID: 22040876 DOI: 10.1248/bpb.34.1659] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Heat shock protein (HSP) 47 may play an important role in the pathogenesis of intestinal fibrosis. Daikenchuto (DKT), a traditional Japanese herbal (Kampo) medicine, has been reported to ameliorate intestinal inflammation. The aims of this study were to determine time-course profiles of several parameters of fibrosis in a rat model, to confirm the HSP47-expressing cells in the colon, and finally to evaluate DKT's effects on intestinal fibrosis. Colitis was induced in male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid (TNBS). HSP47 localization was determined by immunohistochemistry. Colonic inflammation and fibrosis were assessed by macroscopic, histological, morphometric, and immunohistochemical analyses. Colonic mRNA expression of transforming growth factor β1 (TGF-β1), HSP47, and collagen type I were assessed by real time-polymerase chain reaction (PCR). DKT was administered orally once a day from 8 to 14 d after TNBS administration. The colon was removed on the 15th day. HSP47 immunoreactivity was coexpressed with α-smooth muscle actin-positive cells located in the subepithelial space. Intracolonic administration of TNBS resulted in grossly visible ulcers. Colonic inflammation persisted for 6 weeks, and fibrosis persisted for 4 weeks after cessation of TNBS treatment. The expression levels of mRNA and proteins for TGF-β1, HSP47, and collagen I were elevated in colonic mucosa treated with TNBS. These fibrosis markers indicated that DKT treatment significantly inhibited TNBS-induced fibrosis. These findings suggest that DKT reduces intestinal fibrosis associated with decreasing expression of HSP47 and collagen content in the intestine.
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Affiliation(s)
- Ken Inoue
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan
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The effect of traditional Japanese medicine (Kampo) on gastrointestinal function. Surg Today 2010; 40:1105-11. [PMID: 21110152 DOI: 10.1007/s00595-010-4388-8] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2010] [Accepted: 07/26/2010] [Indexed: 12/14/2022]
Abstract
Traditional Japanese medicine (Kampo) is used to treat various disorders of the gastrointestinal tract in Japan, where it is fully integrated into the modern healthcare system. Recently, scientific research on herbal medicine in Japan has been reported in English journals. The objective of the current review is to introduce two traditional Japanese medicines and to provide evidenced-based information regarding their use. Daikenchuto, which consists of three different herbs, is the most frequently prescribed traditional Japanese medicine in Japan. Daikenchuto stimulates gastrointestinal motility though a neural reflex involving presynaptic cholinergic and 5-HT3 receptors. Daikenchuto improves postoperative bowel motility and postoperative ileus. Furthermore, it is reported to cause an increase in gastrointestinal hormones (motilin, vasoactive intestinal peptide, and calcitonin gene-related peptide) and intestinal blood flow. Rikkunshito, a traditional Japanese medicine consisting of eight herbs, is thought to stimulate gastrointestinal motility and ghrelin secretion. Rikkunshito is effective for improving the symptoms of functional dyspepsia, gastroesophageal reflux disease, and cisplatin-induced anorexia and vomiting. Traditional Japanese medicine has the potential to be used successfully in the treatment of gastrointestinal disorders. Details regarding the physiological and clinical effects of traditional Japanese medicine must be further examined in order to become more widely accepted in other countries.
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Manabe N, Camilleri M, Rao A, Wong BS, Burton D, Busciglio I, Zinsmeister AR, Haruma K. Effect of daikenchuto (TU-100) on gastrointestinal and colonic transit in humans. Am J Physiol Gastrointest Liver Physiol 2010; 298:G970-G975. [PMID: 20378829 DOI: 10.1152/ajpgi.00043.2010] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Daikenchuto (TU-100) is a traditional Japanese (Kampo) medicine used to treat postoperative ileus. TU-100 dose dependently increases gastrointestinal (GI) motility by modulating cholinergic and serotonergic mechanisms in animal studies. The aim of this study was to evaluate the effects of orally administered TU-100 on GI and colonic transit and bowel function in healthy humans. In a randomized, parallel-group, double-blind, placebo-controlled, dose-response study, 60 healthy subjects were randomly assigned to placebo or TU-100 2.5 g or 5 g tid ingested immediately before meals for 5 consecutive days. We measured GI and colonic transit by validated scintigraphy and stool frequency and consistency by daily diaries of bowel function. There were overall treatment effects on colonic filling at 6 h without any significant differences between each dose of TU-100 and placebo. There tended to be overall treatment effects on ascending colon (AC) emptying half-time; the TU-100 (7.5 g/day) treatment significantly accelerated AC emptying compared with placebo. There were numerically higher values of GC24 (which reflect overall colonic transit) with both doses of TU-100, but these changes were not statistically significant. There were no significant overall treatment effects on gastric emptying or stool frequency and consistency. One subject, who received 7.5 g/day of TU-100, had elevated creatine phosphokinase following the study. TU-100 (7.5 g/day) significantly accelerated AC emptying. Further randomized controlled trials in patients with functional constipation or irritable bowel syndrome with constipation are warranted to evaluate the clinical efficacy of TU-100 in these disorders.
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Affiliation(s)
- Noriaki Manabe
- Mayo Clinic, Charlton 8-110, 200 First St. S.W., Rochester, MN 55905, USA
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Abstract
Management of functional gastrointestinal disorders is hindered by both poor efficacy and adverse effects of traditional pharmacological therapy. Herbal medicine may be an attractive alternative based on the perception of its 'natural' approach and low risk of side effects; however, the lack of standardization of drug components has limited the ability to perform rigorous clinical studies in Western countries. Japanese herbal medicine (JHM) is a standardized form of herbal medicine with regards to the quality and quantities of ingredients. While extensively studied and widely used in Asia, there is a paucity of data upon which physicians in other parts of the world may draw conclusions regarding the effectiveness of herbal medicine for gastrointestinal disorders. The aim of this study was to summarize the most recent developments in JHM for treatment of functional gastrointestinal disorders. Animal and human studies were systematically reviewed to identify published data of JHM used for treatment of gastrointestinal disorders. The herbal components of JHM were examined. Results describing the physiological and clinical effects of JHM were abstracted, with an emphasis on functional gastrointestinal disorders. JHM are associated with a variety of beneficial physiological on the gastrointestinal system. Patient-based clinical outcomes are improved in several conditions. Rikkunnshi-to reduces symptoms and reverses physiological abnormalities associated with functional dyspepsia, while dai-kenchu-to improves symptoms of postoperative ileus and constipation in children. This updated summary of JHM in the field of gastrointestinal disorders illustrates the potential for herbal medication to serve a valuable role in the management of patients with functional gastrointestinal disorders.
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Affiliation(s)
- H Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
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Kono T, Koseki T, Chiba S, Ebisawa Y, Chisato N, Iwamoto J, Kasai S. Colonic vascular conductance increased by Daikenchuto via calcitonin gene-related peptide and receptor-activity modifying protein 1. J Surg Res 2008; 150:78-84. [PMID: 18561951 DOI: 10.1016/j.jss.2008.02.057] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2007] [Revised: 02/21/2008] [Accepted: 02/25/2008] [Indexed: 01/17/2023]
Abstract
BACKGROUND Daikencyuto (DKT) is a traditional Japanese medicine (Kampo) and is a mixture of extract powders from dried Japanese pepper, processed ginger, ginseng radix, and maltose powder and has been used as the treatment of paralytic ileus. DKT may increase gastrointestinal motility by an up-regulation of the calcitonin gene-related peptide (CGRP). CGRP is also the most powerful vasoactive substance. In the present study, we investigated whether DKT has any effect on the colonic blood flow in rats. MATERIALS AND METHODS Experiments were performed on fasted anesthetized and artificially ventilated Wistar rats. Systemic mean arterial blood pressure and heart rate were recorded. Red blood cell flux in colonic blood flow was measured using noncontact laser tissue blood flowmetry, and colonic vascular conductance (CVC) was calculated as the ratio of flux to mean arterial blood pressure. We examined four key physiological mechanisms underlying the response using blocker drugs: CGRP1 receptor blocker (CGRP(8-37)), nitric oxide synthase inhibitor, vasoactive intestinal polypeptide (VIP) receptor blocker ([4-Cl-DPhe6, Leu17]-VIP), and substance P receptor blocker (spantide). Reverse transcription-polymerase chain reaction was used for the detection of mRNA of calcitonin receptor-like receptor, receptor-activity modifying protein 1, the component of CGRP 1 receptor and CGRP. After laparotomy, a cannula was inserted into the proximal colon to administer the DKT and to measure CVC at the distal colon. RESULTS Intracolonal administration of DKT (10, 100, and 300 mg/kg) increased CVC (basal CVC, 0.10 mL/mmHg) from the first 15-min observation period (0.14, 0.17, and 0.17 mL/mmHg, respectively) and with peak response at either 45 min (0.17 mL/mmHg by 10 mg/kg), or 75 and 60 min (0.23 and 0.21 mL/mmHg by 100 and 300 mg/kg, respectively). CGRP(8-37) completely abolished the DKT-induced hyperemia, whereas nitric oxide synthase inhibitor partially attenuated the DKT-induced hyperemia. [4-Cl-DPhe6, Leu17]-VIP and spantide did not affect the hyperemia. Japanese pepper significantly increased CVC at 45 min or later, whereas ginseng radix only showed a significant increase at 15 min. Reverse transcription-polymerase chain reaction showed that mRNA for calcitonin receptor-like receptor, receptor-activity modifying protein 1, and CGRP were expressed in rat colon and up-regulated by DKT. CONCLUSIONS The present study demonstrated that DKT increased CVC, which was mainly mediated by CGRP and its receptor components.
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Affiliation(s)
- Toru Kono
- Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical College, Hokkaido, Japan.
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Sato Y, Katagiri F, Itoh H, Takeyama M. Bushi-richu-to Raises Calcitonin Gene-related Peptide, Substance P, Somatostatin, and Vasoactive Intestinal Polypeptides Levels in Human Plasma. ACTA ACUST UNITED AC 2007. [DOI: 10.1248/jhs.53.615] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Endo S, Nishida T, Nishikawa K, Nakajima K, Hasegawa JI, Kitagawa T, Ito T, Matsuda H. Dai-kenchu-to, a Chinese herbal medicine, improves stasis of patients with total gastrectomy and jejunal pouch interposition. Am J Surg 2006; 192:9-13. [PMID: 16769267 DOI: 10.1016/j.amjsurg.2006.01.022] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2005] [Revised: 01/21/2006] [Accepted: 01/21/2006] [Indexed: 01/13/2023]
Abstract
BACKGROUND Intestinal motility after gastric surgery frequently is disturbed and results in postoperative intestinal symptoms and poor quality of life (QOL). The purpose of this study was to examine the effects of Dai-kenchu-to on intestinal motility and postoperative QOL of patients. METHODS Seventeen patients who underwent total gastrectomy with jejunal pouch interposition for gastric cancer in the Department of Surgery of Osaka University Medical Hospital were enrolled. The patients were assigned randomly to the cross-over study with or without 15 g/d of Dai-kenchu-to. Questionnaires and emptying tests using (111)In-labeled liquid and (99m)Tc-labeled solid test meal were performed at the end of each treatment period. A manometric study was performed in 6 patients to measure contractile activity with or without Dai-kenchu-to. RESULTS Stasis-related symptoms were reduced significantly by Dai-kenchu-to (P = .032). In the emptying test, Dai-kenchu-to accelerated emptying of both liquid (P < .01) and solid (P = .015) meals from the pouch. The pouch showed bursts of contractions, which were increased significantly by oral intake of Dai-kenchu-to (P = .028). CONCLUSIONS Dai-kenchu-to increased intestinal motility and decreased postoperative symptoms of patients with total gastrectomy with jejunal pouch interposition.
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Affiliation(s)
- Shunji Endo
- Department of Surgery, E1, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-shi, Osaka 565-0871 Japan
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Sato Y, Inoue S, Katagiri F, Itoh H, Takeyama M. Effects of pirenzepine on Dai-kenchu-to-induced elevation of the plasma neuropeptide levels in humans. Biol Pharm Bull 2006; 29:166-71. [PMID: 16394532 DOI: 10.1248/bpb.29.166] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Dai-kenchu-to has been used for the treatment of abdominal obstructions, including bowel obstructions and a feeling of coldness in the abdomen. We reported that Dai-kenchu-to increases plasma neuropeptide [motilin, vasoactive intestinal polypeptide (VIP), serotonin, calcitonin gene-related peptide (CGRP), and substance P]-like immunoreactive substances (IS) levels and that its pharmacologic effects on the gastrointestine are due to changes in gastrointestinal mucosa-regulatory peptide levels. We examined the effects of the selective M(1) muscarinic receptor antagonist pirenzepine on the elevation of Dai-kenchu-to-induced plasma neuropeptide (gastrin, motilin, somatostatin, VIP, CGRP, substance P)-IS levels in human volunteers and the area under the plasma neuropeptide concentration-time curve from 0 to 240 min (AUC(0-->240 min)), which were calculated from the plasma neuropeptide concentration-time curves from each volunteers. Oral pretreatment with pirenzepine reduced the Dai-kenchu-to-induced elevation of plasma motilin and VIP-IS levels and AUC(0-->240 min). Combined treatment with Dai-kenchu-to and pirenzepine increased plasma somatostatin-IS levels and decreased plasma gastrin-IS levels and had no effects on plasma CGRP- and substance P-IS levels and AUC(0-->240 min) compared with administration of Dai-kenchu-to alone. Dai-kenchu-to appeared to induce the release of motilin and VIP into plasma mainly through the activation of M(1) muscarinic receptors, and pirenzepine may affect the pharmacologic action of Dai-kenchu-to by elevation of plasma motilin and VIP levels.
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Affiliation(s)
- Yuhki Sato
- Department of Clinical Pharmacy, Oita University Hospital, Oita, Japan.
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Sato Y, Katagiri F, Inoue S, Itoh H, Takeyama M. Dai-kenchu-to raises levels of calcitonin gene-related peptide and substance P in human plasma. Biol Pharm Bull 2005; 27:1875-7. [PMID: 15516741 DOI: 10.1248/bpb.27.1875] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Sensory afferent neurons in the gastrointestinal mucosa regulate neuropeptides [calcitonin gene-related peptide (CGRP), substance P, etc.], which play various physiologic roles and are gastroprotective. To determine whether the pharmacologic effects of Dai-kenchu-to (DKCT) on the gastrointestine are due to changes in gastrointestinal mucosa regulatory peptide levels, we examined the effects of the DKCT on the levels of CGRP-like immunoreactive substances (IS) and substance P-IS in plasma taken from five healthy subjects. A single oral administration of DKCT 7.5 g caused significant increases in plasma CGRP-IS at 40 min, and in substance P-IS levels at 20 and 60 min, compared with a placebo group. The present study may indicate that the pharmacologic action of DKCT is closely related to changes in CGRP- and substance P-IS levels.
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Affiliation(s)
- Yuhki Sato
- Department of Clinical Pharmacy, Oita University Hospital, Oita, Japan.
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Saida Y, Sumiyama Y, Nagao J, Nakamura Y, Nakamura Y, Katagiri M. DAI-KENCHU-TO, A HERBAL MEDICINE, IMPROVES PRECOLONOSCOPY BOWEL PREPARATION WITH POLYETHYLENE GLYCOL ELECTROLYTE LAVAGE: RESULTS OF A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL. Dig Endosc 2005. [DOI: 10.1111/j.1443-1661.2005.00428.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/23/2023]
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Katagiri F, Inoue S, Sato Y, Itoh H, Takeyama M. Comparison of the effects of Sho-hange-ka-bukuryo-to and Nichin-to on human plasma adrenocorticotropic hormone and cortisol levels with continual stress exposure. Biol Pharm Bull 2004; 27:1679-82. [PMID: 15467219 DOI: 10.1248/bpb.27.1679] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Sho-hange-ka-bukuryo-to and Nichin-to, traditional Chinese herbal (Kampo) medicines have been used to treat vomiting and nausea. Traditional herbal medicines have frequently been used in the empirical treatment. Some patients who take these medicines have no organic disease but have conditions classified as non-ulcer dyspepsia (NUD). To determine the pharmacological effects of Sho-hange-ka-bukuryo-to, Nichin-to, and the two herbs (Pinelliae Tuber and Zingiberis Rhizoma, both of which are included in Sho-hange-ka-bukuryo-to and Nichin-to), we examined the effects of these medicines on the plasma levels of adrencorticotropic hormone (ACTH) and cortisol under stress conditions by repetitive blood sampling. After a single administration of Kampo medicine or a placebo, venous blood samples were taken before and 20-240 min after administration. A single administration of Sho-hange-ka-bukuryo-to caused significant suppression of an increase in plasma ACTH-immunoreactive substance (IS) levels at 120 to 180 min and tended to suppress increases in plasma cortisol levels at 240 min, compared with the response to a placebo. A single administration of Nichin-to caused significant suppression of increases in plasma ACTH-IS levels at 120 min compared with a placebo group, but had no effect on plasma cortisol levels. Pinelliae Tuber had no significant effects in plasma ACTH-IS or cortisol, but Zingiberis Rhizoma significantly suppressed the increase of ACTH-IS (120 min) and cortisol (180 min). These medicines have a modulatory effect on the hypothalamo-pituitary-adrenal (HPA) axis and autonomic nervous function. These effects might be beneficial in stress-related disease and suggest that this medicine has clinical pharmacological activity.
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Affiliation(s)
- Fumihiko Katagiri
- Department of Clinical Pharmacy, Oita University Hospital, Hasama-machi, Japan.
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Katagiri F, Itoh H, Takeyama M. Effect of Sho-hange-ka-bukuryo-to on Gastrointestinal Peptide Concentrations in the Plasma of Healthy Human Subjects. Biol Pharm Bull 2004; 27:1674-8. [PMID: 15467218 DOI: 10.1248/bpb.27.1674] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Sho-hange-ka-bukuryou-to, a traditional Chinese herbal (Kampo) medicine, has been used to treat hyperemesis of pregnancy, nausea and vomiting. Most traditional herbal medicines are prepared from several herbs. For example, Sho-hange-ka-bukuryo-to is prepared from three herbs: Pinelliae Tuber, Zingiberis Rhizoma and Hoelen. Thus, to determine the precise mechanism of the pharmacological effects of Chinese herbal medicines is too difficult. So we have elucidated the effect of some Chinese herbal medicines by examining the change of the plasma levels of brain-gut peptides. In this study, we investigated the effects of Sho-hange-ka-bukuryo-to on the plasma levels of gut-regulated peptides (gastrin, somatostatin, motilin and vasoactive intestinal peptide (VIP)) and gastrointestinal mucosa regulatory neuropeptides (calcitonin gene-related peptide (CGRP) and substance P) in healthy human subjects. A single oral administration of Sho-hange-ka-bukuryo-to caused significant increases in plasma somatostatin-, CGRP- and substance P-immunoreactive substance (IS) levels, compared with a placebo group. Transient elevation of gastrin-IS levels in the placebo group was inhibited by the administration of Sho-hange-ka-bukuryo-to, but the medicine showed no effects on plasma motilin- or VIP-IS levels. In conclusion, these results might indicate that the pharmacological action of Sho-hange-ka-bukuryo-to is closely related to changes in gastrin-, somatostatin-, CGRP- and substance P-IS levels in human plasma.
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Affiliation(s)
- Fumihiko Katagiri
- Department of Clinical Pharmacy, Oita University Hospital, Hasama-machi, Japan.
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Sato Y, Katagiri F, Inoue S, Itoh H, Takeyama M. Effects of Ninjin-to on Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma. Biol Pharm Bull 2004; 27:2032-4. [PMID: 15577227 DOI: 10.1248/bpb.27.2032] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The herbal medicine Ninjin-to has been used for the treatment of gastroenteritis, esogastritis, gastric atony, gastrectasis, vomiting, and anorexia. One of the mechanisms of the empirical effects is assumed to be due to local changes in neuropeptide levels. Sensory afferent neurons in the gastrointestinal mucosa regulate neuropeptides [calcitonin gene-related peptide (CGRP), substance P, etc.], which play various physiologic roles. To determine whether the pharmacologic effects of Ninjin-to on the gastrointestine are due to changes in gastrointestinal mucosa regulatory peptide levels, we examined the effects of Ninjin-to on the levels of CGRP-like immunoreactive substances (IS) and substance P-IS in plasma taken from five healthy subjects. A single oral administration of 6.0 g of Ninjin-to caused significant increases in plasma CGRP-IS at 40 min and 60 min, and in substance P-IS levels at 90 min, compared with a placebo group. These results may indicate that the pharmacologic actions of Ninjin-to are closely related to changes in CGRP-IS and substance P-IS levels.
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Affiliation(s)
- Yuhki Sato
- Department of Clinical Pharmacy, Oita University Hospital, Japan.
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Ohya T, Usui Y, Arii S, Iwai T, Susumu T. Effect of dai-kenchu-to on obstructive bowel disease in children. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2003; 31:129-35. [PMID: 12723762 DOI: 10.1142/s0192415x03000710] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The aim of this study was to evaluate the effects of a traditional Chinese herbal medicine, dai-kenchu-to (DKT), on obstructive bowel diseases in children. We have treated 46 pediatric patients with various obstructive bowel diseases with DKT: six patients with postoperative ileus, 12 with large abdominal surgery (including three neonates), one with ano-rectal anomaly, three with Hirschsprung's disease, two with functional bowel obstructions, one with SMA syndrome, and 21 patients with chronic constipation. DKT (0.1-0.15 g/kg) was mixed with 5-10 ml of warm water, and was given orally two to three times a day. DKT was effective for 39 patients (85%) and their clinical symptoms improved. DKT was ineffective in seven patients: two with postoperative ileus, two with Hirschsprung's disease, and three with chronic constipation. DKT had mild but significant effects for various obstructive bowel diseases in children, while no side effects were encountered. Our current strategy for pediatric patients with obstructive bowel disease is to use DKT first and then test its efficacy. If DKT is effective, the regimen is continued. However, in cases where DKT is not effective, we will consider laparotomy or will further investigate the illness.
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Affiliation(s)
- Toshiki Ohya
- Department of Surgery, Tokyo Medical and Dental University, School of Medicine 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
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Naito T, Itoh H, Takeyama M. Comparison of the effects of hange-shashin-to and rikkunshi-to on human plasma calcitonin gene-related peptide and substance P levels. Biol Pharm Bull 2003; 26:1104-7. [PMID: 12913259 DOI: 10.1248/bpb.26.1104] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Regarding the gastroprotective function as a neural emergency system, sensory afferent neurons in the gastrointestinal mucosa regulate neuropeptide (calcitonin gene-related peptide (CGRP), substance P, etc.) levels, and those peptides play various physiological roles. To determine whether the pharmacological effects of Hange-shashin-to and Rikkunshi-to on the gastrointestine are due to changes in gastrointestinal mucosa regulatory peptides levels, we investigated the levels of CGRP-like immunoreactive substances (IS) and substance P-IS in plasma from healthy subjects. A single oral administration of Hange-shashin-to caused significant increases in CGRP-IS (40-60 min) and substance P-IS (60-180 min) levels in the plasma compared with the levels induced by a placebo. Rikkunshi-to and a 5.0 g Pinelliae tuber extract had no significant effect on CGRP-IS and substance P-IS levels. Extract of a 2.5 g Zingiberis rhizoma significantly caused increases in CGRP-IS at 40 min and in substance P-IS at 60 min. These results, in comparison with Kampo medicines, might indicate that the pharmacological actions of Hange-shashin-to closely are related to changes in CGRP-IS and substance P-IS levels, while Zingiberis rhizoma partially might participate in those effects of Hange-shashin-to.
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Affiliation(s)
- Takafumi Naito
- Department of Clinical Pharmacy, Oita Medical University
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Naito T, Itoh H, Takeyama M. Some gastrointestinal function regulatory Kampo medicines have modulatory effects on human plasma adrenocorticotropic hormone and cortisol levels with continual stress exposure. Biol Pharm Bull 2003; 26:101-4. [PMID: 12520183 DOI: 10.1248/bpb.26.101] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Rikkunshi-to, a gastrointestinal function regulatory traditional Chinese herbal (Kampo) medicine, has recently been evaluated for its clinical usefulness in stress and depression. This medicine has modulatory effects on the hypothalamo-pituitary-adrenal axis and autonomic nervous function. We examined the effect of Rikkunshi-to and the other gastrointestinal function regulatory Kampo medicines, Hange-shashin-to, Hange-koboku-to, and Ninjin-to, on the plasma levels of adrenocorticotropic hormone (ACTH) and cortisol under stress conditions by repetitive blood sampling. Rikkunshi-to, Hange-shashin-to, and Hange-koboku-to significantly suppressed increases in plasma ACTH-immunoreactive substance (IS) levels compared with the response to a placebo. Rikkunshi-to and Hange-shashin-to significantly suppressed increases in plasma cortisol levels compared with the response to placebo. Ninjin-to had no significant effect on plasma ACTH-IS and cortisol levels. In this study, Rikkunshi-to, Hange-shashin-to, and Hange-koboku-to (partially) regulated plasma ACTH and cortisol levels under stress. These modulatory effects might be beneficial in stress-related disease and suggest that these medicines have clinical pharmacologic activity.
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Affiliation(s)
- Takafumi Naito
- Department of Clinical Pharmacy, Oita Medical University, Hasama-machi, Oita 879-5593, Japan.
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Abstract
AIM: To investigate the relationship among gastrin, somatostatin, G and D cells in gastric ulcer and in its healing process in rats.
METHODS: Fourty-nine Wistar rats were divided into 7 groups. The gastric ulcer model was induced by acetic acid successfully. The gastrin and the somatostatin in rat plasma, gastric fluid and antral tissue were measured by radioimmunoassay (RIA). G and D cells in antral mucosa were analyzed with polyclonal antibody of gastrin and somatostatin by immunohistochemical method and Quantimet 500 image analysis system.
RESULTS: In gastric ulcer, the level of gastrin in plasma, gastric fluid, and antral tissue increased, that of somatostatin declined, and the disorder gradually recovered to the normal level in the healing process. Immunohistochemical technique of G and D cells in antral mucosa demonstrated that the number of G cells increased and that of D cells decreased, both areas of G and D cells declined, the ratio of number and area of G/D increased in gastric ulcer, and the disorder gradually recovered in the healing process.
CONCLUSION: In gastric ulcer, the increased gastrin secreted by G cells, the declined somatostatin secreted by D cells, and the disordered G/D cell ratio can lead to gastrointestinal dysfunction.
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Affiliation(s)
- Feng-Peng Sun
- Department of Gastroenterology, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, Guangdong Province, China.
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Murata P, Kase Y, Ishige A, Sasaki H, Kurosawa S, Nakamura T. The herbal medicine Dai-kenchu-to and one of its active components [6]-shogaol increase intestinal blood flow in rats. Life Sci 2002; 70:2061-70. [PMID: 12148698 DOI: 10.1016/s0024-3205(01)01552-1] [Citation(s) in RCA: 60] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
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.
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Affiliation(s)
- Pin Murata
- R & D Division, Tsumura & Co, Ibaraki, Japan.
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Naito T, Itoh H, Yasunaga F, Takeyama M. Hange-shashin-to raises levels of somatostatin, motilin, and gastrin in the plasma of healthy subjects. Biol Pharm Bull 2002; 25:327-31. [PMID: 11913527 DOI: 10.1248/bpb.25.327] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Hange-shashin-to has been used for chronic hypofunction of the gastrointestinal tract and to improve functional abnormalities of the upper and lower gastrointestinal system. To determine whether the pharmacological effects of Hange-shashin-to are due to gut-regulatory peptide levels, we developed a sensitive and specific double-antibody enzyme immunoassay (EIA) for detecting motilin and also examined the levels of somatostatin-, motilin-, gastrin-, and vasoactive intestinal peptide (VIP)-immunoreactive substances (IS) in plasma from healthy subjects. We developed a sensitive (3.5 pg, 1.4 pg/well) and specific (carboxy-terminal region) EIA for motilin. A single oral administration of Hange-shashin-to 6.0 g caused significant increases somatostatin-IS (20-60 min), motilin-IS (40 min), and gastrin-IS (40-90 min) levels in plasma compared with levels in a placebo group. Hange-shashin-to had no significant effect on VIP-IS levels after single administration. These changes in hormone levels (somatostatin, motilin, and gastrin) might relate to normalization of the upper and lower gastrointestinal system by Hange-shashin-to.
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Affiliation(s)
- Takafumi Naito
- Department of Clinical Pharmacy, Oita Medical University, Hasama-machi, Japan.
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Naito T, Itoh H, Yasunaga F, Takeyama M. Rikkunshi-to raises levels of somatostatin and gastrin in human plasma. Biol Pharm Bull 2001; 24:841-3. [PMID: 11456128 DOI: 10.1248/bpb.24.841] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Rikkunshi-to, a traditional Chinese (Kampo) medicine, has been used to treat chronic hypofunctions of the gastrointestinal tract. The effects of Rikkunshi-to on the plasma levels of gut-regulated peptide (somatostatin, motilin, gastrin, and vasoactive intestinal peptide (VIP)) levels were studied in healthy subjects. A single oral administration of Rikkunshi-to caused significant increases in plasma somatostatin and gastrin levels at 60 to 240 min compared with a placebo group. On the other hand, this medicine showed no effects on motilin and VIP levels. In conclusion, these results might indicate that the pharmacological action of Rikkunshi-to is closely related to changes in somatostatin- and gastrin-immunoreactive substance levels.
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Affiliation(s)
- T Naito
- Department of Clinical Pharmacy, Oita Medical University, Hasamu-machi, Japan.
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Naito T, Itoh H, Nagano T, Takeyama M. Effects of Ninjin-to on levels of brain-gut peptides (motilin, vasoactive intestinal peptide, gastrin, and somatostatin) in human plasma. Biol Pharm Bull 2001; 24:194-6. [PMID: 11217092 DOI: 10.1248/bpb.24.194] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
We examined the effects of Ninjin-to, a traditional Chinese (Kampo) medicine, on the levels of brain-gut peptides (motilin, vasoactive intestinal peptide (VIP), gastrin, and somatostatin) in plasma from healthy subjects. A single oral administration of Ninjin-to, at a dose of 6.0 g, caused significant increases in plasma motilin levels at 40 to 90 min and somatostatin levels at 20 to 90 min, compared with a placebo treated group. Transient elevations of gastrin levels in the placebo group were inhibited by administration of Ninjin-to, but the medicine did not alter the levels of VIP. In conclusion, these results suggest that pharmacological effects of Ninjin-to on gastrointestinal functions closely relate to changes of motilin, gastrin, and somatostatin-immunoreactive substance levels in human plasma.
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Affiliation(s)
- T Naito
- Department of Clinical Pharmacy, Oita Medical University, Hasama-machi, Japan.
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