• Medicine, Chinese Traditional
• Humans
• Drugs, Chinese Herbal/therapeutic use
• Drugs, Chinese Herbal/chemistry
• Clinical Trials as Topic
• Meta-Analysis as Topic
• Databases, Factual
• User-Computer Interface

• 2021YFC2500203 National Key R&D Program of China
• 32070670 National Natural Science Foundation of China
• L222007 Beijing Natural Science Foundation
• 2023030615 Ningbo major project for high-level medical and healthcare teams
• 2024Z229 Ningbo Science and Technology Innovation Yongjiang 2035 Project
• GZNL2023A03001 Major Project of Guangzhou National Laboratory
• National Key R&D Program of China

• Humans
• Phytotherapy/standards
• Phytotherapy/methods
• Gastrointestinal Diseases/therapy
• Gastrointestinal Diseases/drug therapy
• Practice Guidelines as Topic
• Evidence-Based Medicine
• Treatment Outcome
• Germany

• Duodenal-jejunal bypass (DJB)
• TU-100
• inflammatory cytokines

• Animals
• Male
• Duodenum/surgery
• Jejunum/surgery
• Gastrointestinal Microbiome/drug effects
• Rats
• Plant Extracts/pharmacology
• Zingiberaceae
• Panax
• Postoperative Period
• Zanthoxylum
• Rats, Sprague-Dawley
• Blood Glucose/drug effects
• Diabetes Mellitus, Experimental/surgery
• Cytokines/metabolism

• bile acid
• constipation
• visceral sensitivity

• Humans
• Aged
• Prospective Studies
• Constipation/drug therapy
• Constipation/chemically induced
• Dipeptides/adverse effects
• Thiazepines/adverse effects
• Bile Acids and Salts/therapeutic use

• EA Pharma Co., Ltd.
• Mochida Pharmaceutical Company

Daikenchuto (DKT) is one of the most widely used Japanese herbal formulae for various gastrointestinal disorders. It consists of Zanthoxylum Fructus (Japanese pepper), Zingiberis Siccatum Rhizoma (processed ginger), Ginseng radix, and maltose powder. However, the use of DKT in clinical settings is still controversial due to the limited molecular evidence and largely unknown therapeutic effects. Here, we investigated the anti-inflammatory actions of DKT in the dextran sodium sulfate (DSS)-induced colitis model in mice. We observed that DKT remarkably attenuated the severity of experimental colitis while maintaining the members of the symbiotic microbiota such as family Lactobacillaceae and increasing levels of propionate, an immunomodulatory microbial metabolite, in the colon. DKT also protected colonic epithelial integrity by upregulating the fucosyltransferase gene Fut2 and the antimicrobial peptide gene Reg3g. More remarkably, DKT restored the reduced colonic group 3 innate lymphoid cells (ILC3s), mainly RORγt^high-ILC3s, in DSS-induced colitis. We further demonstrated that ILC3-deficient mice showed increased mortality during experimental colitis, suggesting that ILC3s play a protective function on colonic inflammation. These findings demonstrate that DKT possesses anti-inflammatory activity, partly via ILC3 function, to maintain the colonic microenvironment. Our study also provides insights into the molecular basis of herbal medicine effects, promotes more profound mechanistic studies towards herbal formulae and contributes to future drug development.

• Daikenchuto (DKT)
• Japanese herbal medicine (Kampo medicine)
• Lactobacillaceae
• biomolecular functions of herbal medicine
• colonic homeostasis
• experimental colitis
• group 3 innate lymphoid cells (ILC3s)
• gut microbiota

• Daikenchuto
• Gut microbiota
• Intestinal contraction
• Kampo medicine
• Objective marker
• Statistical pattern recognition

Approximately 60% of patients with chronic constipation (CC) have a significantly higher rate of loss of defecation desire (LODD). Bile acids are expected to have a restorative effect on defecation desire (DD) because they lower the rectal sensory threshold, which is an objective index of DD. Elobixibat (EXB) specifically inhibits the ileal bile acid transporter/apical sodium-dependent bile acid transporter, which is a transporter involved in the reabsorption of bile acids in the terminal ileum. This study aims to investigate the LODD improvement rate in patients with CC after 4 weeks of EXB treatment.

A total of 40 adult patients with CC who meet the eligibility criteria will be enrolled. Patients will receive oral EXB (10 mg/day) for 4 weeks. A patient diary will be provided daily at 4 weeks after treatment. The primary endpoint will be the percentage LODD improvement at week 4 of the treatment period from week 2 of the observation period using questionnaires.

Ethical approval was obtained from the Yokohama City University Certified Institutional Review Board prior to participant enrolment (approval number: CRB21-008). The results of this study will be submitted for publication in international peer-reviewed journals, and key findings will be presented at international scientific conferences. Participants desiring the results of this study will be directly contacted for data dissemination.

This trial was registered at ClinicalTrials.gov (NCT05165199).

1.0, September 21, 2021.

Japanese Kampo medicine is a traditional medicine with roots in ancient Chinese medicine. Because traditional physicians had been abolished in Japan, the present mainstream of Kampo treatment is that physicians who learned modern Western medicine prescribe Kampo extract products based on Western medical diagnosis. This situation is different from that in other east Asian countries, and the physicians require scientific clinical evidence.

Clinical studies were searched from literature databases, clinical trial registry sites, and “Evidence Reports of Kampo Treatment (EKAT)” published by the Japan Society for Oriental Medicine.

At the approval of Kampo products, scientific clinical evidence was not required because they have a long-period experience as a decoction. However, in the 1990s, Kampo products became a subject for national reevaluation; double-blind and placebo-controlled clinical trials. At the time, a methodological foundation for conducting clinical assessments of Kampo medicines was established. From 2000 onwards, with the evidence-based medicine era, the field of Kampo medicine also saw many randomized controlled trials, and their evidence was collected and published as EKAT. In the 2010s, post-marketing clinical trials of Kampo products also had to be conducted in this environment due to the need for ethical and scientific assurance. Currently, there are numerous clinical trials of Kampo products being conducted with high-grade trial designs.

The situation of Kampo clinical studies reflects the unique history and position of Kampo medical system and Kampo products in Japan.

• Clinical study
• Clinical trial registry
• Kampo medicine
• Randomized controlled trial
• Reevaluation

• daikenchuto
• eosinophil
• inflammatory bowel disease
• visceral pain

• Hyogo College of Medicine

This study aimed to elucidate the effect of the extract of daikenchuto (DKT), a Japanese Kampo medicine, on the contractile activity of the internal anal sphincter in conscious dogs.

Force transducers were attached to the serosal surface of the rectum and the internal anal sphincter of male beagle dogs. In addition, the contractile activity of the rectum and the internal anal sphincter was continuously measured until 6 h after DKT administration via telemetry in the conscious state. The DKT dose was 1.5 g/body, and the administration route was intrarectal in the expectation of a direct effect on the rectoanal region. DKT was re-administered to the same animal after drug withdrawal, and the plasma concentrations of hydroxy-α-sanshool (HAS) and hydroxy-β-sanshool (HBS) before and after administration were measured.

After DKT administration, the contractile activity of the internal anal sphincter immediately increased, peaked at 10 min, continued for ≥1 h, and had almost disappeared after 4 h. Rectal contraction differed from that of the internal anal sphincter, with no significant contraction observed. HAS and HBS were found in the plasma of animals administered with DKT and persisted up to 2 h after the administration.

This is the first report on in vivo telemetry demonstrating that DKT exhibited contractile effects on the dog's internal anal sphincter. The increased anal pressure and improvement of fecal incontinence symptoms observed in previous clinical studies may have been based on this sphincter contraction.

• daikenchuto
• fecal incontinence
• internal anal sphincter
• telemetry system

• chronic idiopathic constipation
• economic burden
• functional constipation
• health-related quality of life

• QOL
• daikenchuto
• gynecological cancer
• ileus
• surgery

• Delphi process
• chronic constipation
• guidelines
• management of constipation

• Adult
• Colonic Diseases, Functional/therapy
• Constipation/therapy
• Female
• Humans
• Male

Objectives: The purpose of this study was to investigate whether the symptoms of fecal incontinence (FI) or anal sphincter dysfunction are improved by daikenchuto (DKT). Methods: This is a retrospective observational study that analyzes the effects of DKT. The study was conducted at Kunimoto Hospital. Patients who visited the hospital from January 2012 to December 2016 due to symptoms of FI with a certain degree of chronic constipation and who took DKT were enrolled. The drug to be evaluated was “Tsumura Daikenchuto Extract Granules for Ethical Use (TJ-100)” manufactured by Tsumura & Co., Tokyo, Japan. The primary outcome measures were changes in the scores of the Cleveland Clinic Incontinence Score (CCIS) and Constipation Scoring System (CSS) before and after the administration of DKT. Results: A total of 157 patients were enrolled. On the CCIS, “leakage of solid stool,” “leakage of liquid stool,” “pad use,” and “total score” were significantly improved. On the contrary, on the CSS, the score of “type of assistance” was significantly improved after the administration of DKT, but no significant difference was found in the total score. On the Bristol Stool Form Scale, the administration of DKT showed a tendency to normalize stool consistency. Maximum resting anal pressure and maximum squeeze anal pressure significantly increased after the administration of DKT. No side effects caused by DKT were observed during the study. Conclusions: DKT appears to be a safe and useful agent for the management of FI in patients with defecation disorders and internal anal sphincter dysfunction.

• chronic constipation
• daikenchuto
• fecal incontinence
• resting anal pressure
• stool form scale

Daikenchuto (DKT) is a Kampo medicine used for the treatment of constipation. In this study, we evaluated the effectiveness of DKT against constipation.

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.

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.

We suggest that DKT increases defaecation frequency and is safe for treating constipation.

• Immunoendocrine axis
• Irritable bowel syndrome
• Low grade inflammation
• Motility
• Secretion
• Therapy

• Abdominal Pain/drug therapy
• Abdominal Pain/immunology
• Abdominal Pain/physiopathology
• Bile Acids and Salts/metabolism
• Clinical Trials as Topic
• Drugs, Investigational/therapeutic use
• Gastrointestinal Agents/therapeutic use
• Gastrointestinal Motility/drug effects
• Humans
• Inflammation/drug therapy
• Inflammation/physiopathology
• Intestines/drug effects
• Intestines/immunology
• Intestines/physiopathology
• Irritable Bowel Syndrome/drug therapy
• Irritable Bowel Syndrome/immunology
• Irritable Bowel Syndrome/physiopathology
• Permeability/drug effects
• Treatment Outcome

• EGF receptor
• Kampo
• adenomatous polyposis coli
• ginseng
• β-catenin

• Animals
• Azoxymethane/chemistry
• Azoxymethane/pharmacology
• Colonic Neoplasms/drug therapy
• Colonic Neoplasms/pathology
• Disease Models, Animal
• Male
• Medicine, Traditional
• Mice
• Panax
• Plant Extracts/administration & dosage
• Plant Extracts/therapeutic use
• Zanthoxylum
• Zingiberaceae

• P30 DK042086 NIDDK NIH HHS
• R01 CA164124 NCI NIH HHS
• P30 CA014599 NCI NIH HHS
• R01 CA036745 NCI NIH HHS
• R37 DK047722 NIDDK NIH HHS
• R01 DK097268 NIDDK NIH HHS
• R37 CA036745 NCI NIH HHS
• R01 DK047722 NIDDK NIH HHS

• Daikenchuto
• gastrointestinal tract
• interstitial cells of Cajal
• pacemaker potentials

• Adrenocorticotropic hormone
• Anxiety
• Colorectal distention
• Dai-kenchu-to
• Visceral pain

To investigate Japanese traditional (Kampo) medicine’s effectiveness on cancer chemotherapy-induced peripheral neuropathy (CIPN), we carried out this retrospective study.

By searching our outpatient database of 3154 patients who consulted our outpatient clinic of Japanese-Oriental (Kampo) Medicine at Chiba University Hospital from November 2005 to December 2010, a total of 281 patients diagnosed with cancer were identified. Twenty-four patients out of the 281 patients identified met the following three conditions and were eligible for further investigation of the effectiveness of Kampo treatment: At least one course of cancer chemotherapy had been administered; numbness and pain appeared after the chemotherapy; and CIPN was diagnosed before they were given Kampo treatment.

The 24 patients included 6 males and 18 females and ranged in age from 39 to 86 (mean 61.2 ± 11.5) years old. Kampo formulas were individually chosen by Kampo expert doctors based on Kampo-specific diagnostics. Beneficial outcomes were obtained by Kampo treatment in 20 out of the 24 cases (83.3%). Nine out 20 cases had a major response (the numbness and pain showed improvement or reduction by 50% or more), with 7 of 9 cases showing a more than 70% symptom reduction. Eleven out of 20 cases showed a minor response (less than 50% symptom reduction), and 4 out of the 24 cases had no beneficial response. The most frequently used formula was goshajinkigan (GJG), followed by hachimijiogan (HJG) and keishibukuryogan. Thirteen of the 24 cases (54.2%) were prescribed aconite root-containing formulas including GJG and HJG. Aconite root has “warming” effects and ameliorates pain and numbness; 21 out of 24 cases (87.5%) in total used warming formulas such as aconite root-containing formulas to reduce CIPN.

Our current study suggested that Kampo formulas chosen based on Kampo-specific diagnostics could be for treating CIPN that is refractory to conventional medicine.

• Asian medicine
• Traditional Chinese medicine
• Goshajinkigan
• Keishibukuryogan
• Hachimijiogan

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

• Bacterial metabolism
• Daikenchuto
• bioavailability
• microbiome
• traditional Japanese medicine

• GLP-1 analogue
• bile acid transporter
• cannabinoid
• chloride channels
• constipation-predominant irritable bowel syndrome
• guanylate cyclase C
• serotonin

• Abdominal Pain/drug therapy
• Abdominal Pain/etiology
• Animals
• Constipation/drug therapy
• Constipation/etiology
• Drug Design
• Drugs, Investigational/adverse effects
• Drugs, Investigational/pharmacology
• Drugs, Investigational/therapeutic use
• Gastrointestinal Agents/adverse effects
• Gastrointestinal Agents/pharmacology
• Gastrointestinal Agents/therapeutic use
• Humans
• Irritable Bowel Syndrome/drug therapy
• Irritable Bowel Syndrome/physiopathology

Daikenchuto (TU 100), a botanical agent that modulates gastrointestinal nerves, is used in the treatment of motility and functional disorders. Our aim was to study the effects of TU-100 on rectal compliance and sensation in patients with irritable bowel syndrome (IBS).

In 20 patients per treatment arm, we conducted a single-center, randomized, parallel-group, double-blind, placebo-controlled, single-dose pharmacodynamics study evaluating the effects of TU-100, 15 g (5 g t.i.d. [means 3 times a day]), for 14–16 consecutive days on rectal compliance and rectal sensation (thresholds and sensation ratings), all measured at baseline and on the last day of medication treatment. The primary endpoint was rectal sensation thresholds and sensation ratings in response to balloon distension at 32 mmHg. Secondary endpoints were rectal compliance, sensation thresholds, ratings and tone (fasting and postprandial), bowel pattern, abdominal pain (average and worst severity) and bloating scores, IBS quality of life and safety profile.

Rectal sensation ratings post-treatment were significantly associated with baseline (pre-treatment) ratings and with level of anxiety or stress recorded at the time of the sensation testing. There were no effects of TU-100 treatment on rectal sensation ratings, sensation thresholds, rectal fasting or postprandial tone, rectal compliance, bowel function, abdominal pain or bloating scores, or IBS quality of life.

TU-100 did not significantly affect rectal compliance and sensation in patients with IBS in this study.

• Abdominal pain
• Anxiety
• Humans
• Quality of life

• Daikenchuto
• gingerol
• ginsenosides
• luminal concentration
• shogaol

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.

• Kampo
• adrenomedullin
• daikenchuto
• hydroxy-α-sanshool
• potassium leak channels
• traditional Japanese herbal medicine
• transient receptor potential ankyrin 1

Daikenchuto (DKT), a traditional Japanese herbal medicine, is widely used for treatment of gastrointestinal disorders. We evaluated the efficacy and safety of DKT for abdominal bloating in patients with chronic constipation.

To evaluate the efficacy and safety of DKT for the treatment of abdominal bloating.

After discontinuing as-needed use of laxatives, 10 patients received oral DKT for 14 days (15 g/d). To evaluate small intestinal bacteria overgrowth (SIBO), a glucose breath test was performed before and after treatment with DKT. Before beginning the treatment, 4 patients (40%) had a diagnosis of SIBO based on a positive glucose breath test result. In both the SIBO and non-SIBO groups, bowel movement frequency and stool form remained unchanged after DKT treatment.

For all patients, median total Gastrointestinal Symptoms Rating Scale score and the median Gastrointestinal Symptoms Rating Scale indigestion and constipation subscales were significantly decreased, whereas the median visual analog score for decreased abdominal bloating was significantly increased. Improvements of those symptoms were the same in both the SIBO and non-SIBO groups, indicating that DKT does not have effects on small intestine bacteria. No serious side effects were reported.

DKT treatment improved quality of life for patients with chronic constipation regardless of the presence of SIBO and showed no effects on small intestine bacteria. UMIN Clinical Trial Registry identifier: UMIN000008070.

• abdominal bloating
• chronic constipation
• daikenchuto
• small intestinal bacterial overgrowth

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.

• Kampo
• constipation
• herb
• herbal medicine
• traditional medicine

Irritable bowel syndrome with constipation and chronic functional constipation are common digestive disorders that negatively impact quality of life and account for billions of dollars in health care costs. Related to the heterogeneity of pathogenesis that underlie these disorders and the failure of symptoms to reliably predict underlying pathophysiology, traditional therapies provide relief to only a subset of affected individuals. The evidence surrounding new and emerging pharmacologic treatments, which include both luminally and systemically acting drugs, is discussed here. These include agents such as lubiprostone, bile acid modulations, guanylate cyclase-C receptor agonists, serotonin receptor modulators and herbal therapies.

• Bile acid and salts
• Constipation
• Irritable bowel syndrome
• Laxatives
• Therapeutics

• Animals
• Antibodies, Monoclonal/adverse effects
• Antibodies, Monoclonal/immunology
• Apoptosis/drug effects
• CD3 Complex/immunology
• Cell Line, Tumor
• Enteritis/chemically induced
• Enteritis/drug therapy
• Enteritis/immunology
• Enteritis/metabolism
• Enzyme Activation/drug effects
• Zingiber officinale/chemistry
• Humans
• Intestinal Mucosa/drug effects
• Intestinal Mucosa/pathology
• Jejunum/drug effects
• Jejunum/immunology
• Jejunum/pathology
• Mice
• NF-kappa B/metabolism
• Panax
• Plant Extracts/pharmacology
• Plant Extracts/therapeutic use
• Proto-Oncogene Proteins c-akt/metabolism
• Specific Pathogen-Free Organisms
• T-Lymphocytes/drug effects
• T-Lymphocytes/immunology
• Tumor Necrosis Factor-alpha/metabolism
• Zanthoxylum
• Zingiberaceae

• UL1 TR000430 NCATS NIH HHS
• P30 DK042086 NIDDK NIH HHS
• R01 CA164124 NCI NIH HHS
• K01 AT005362 NCCIH NIH HHS
• R01 CA036745 NCI NIH HHS
• P01 AT004418 NCCIH NIH HHS
• R37 DK047722 NIDDK NIH HHS
• DK097268 NIDDK NIH HHS
• R01 DK047722 NIDDK NIH HHS
• AT004418 NCCIH NIH HHS
• CA036745 NCI NIH HHS
• DK47722 NIDDK NIH HHS
• AT005362 NCCIH NIH HHS
• R01 DK097268 NIDDK NIH HHS
• P30 DK42086 NIDDK NIH HHS
• R37 CA036745 NCI NIH HHS