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Front Pharmacol. 2015 Aug 04;6:159. doi: 10.3389/fphar.2015.00159. eCollection 2015.

Complementary and synergistic therapeutic effects of compounds found in Kampo medicine: analysis of daikenchuto.

Frontiers in pharmacology

Toru Kono, Mitsuo Shimada, Masahiro Yamamoto, Atushi Kaneko, Yuji Oomiya, Kunitsugu Kubota, Yoshio Kase, Keiko Lee, Yasuhito Uezono

Affiliations

  1. 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.
  2. Department of Surgery, Institute of Health Biosciences, Graduate School of Medicine, Tokushima University Tokushima, Japan.
  3. Kampo Scientific Strategies Division, Tsumura Research Laboratories, Tsumura & CO. Ami, Japan.
  4. Kampo Scientific Strategies Division, International Pharmaceutical Development Department, Tsumura & CO. Tokyo, Japan.
  5. Division of Cancer Pathophysiology, National Cancer Center Research Institute Tokyo, Japan.

PMID: 26300774 PMCID: PMC4523940 DOI: 10.3389/fphar.2015.00159

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.

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

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