Increased levels of circulating adrenomedullin following treatment with TU‑100 in patients with Crohn's disease

Kominato,Ken; Yamasaki,Hiroshi; Mitsuyama,Keiichi; Takedatsu,Hidetoshi; Yoshioka,Shinichiro; Kuwaki,Kotaro; Kobayashi,Teppei; Yamauchi,Ryosuke; Fukunaga,Shuhei; Tsuruta,Osamu; Torimura,Takuji

doi:10.3892/mmr.2016.5488

Increased levels of circulating adrenomedullin following treatment with TU‑100 in patients with Crohn's disease

Authors:
- Ken Kominato
- Hiroshi Yamasaki
- Keiichi Mitsuyama
- Hidetoshi Takedatsu
- Shinichiro Yoshioka
- Kotaro Kuwaki
- Teppei Kobayashi
- Ryosuke Yamauchi
- Shuhei Fukunaga
- Osamu Tsuruta
- Takuji Torimura
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Affiliations: Inflammatory Bowel Disease Center, Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
Published online on: July 8, 2016 https://doi.org/10.3892/mmr.2016.5488
Pages: 2264-2268

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Abstract

Daikenchuto (TU‑100) is a traditional Japanese medicine that is widely used to treat intestinal symptoms. The mechanisms underlying it effects on the circulating levels of adrenomedullin (ADM) are of interest. In addition, the effect of TU‑100 in the treatment of Crohn's disease (CD) in humans remains to be elucidated. The primary objective of the present study was to evaluate the effect of TU‑100 on the circulating ADM levels in patients with active CD. An additional objective was to assess the effect of the drug on the disease activity and its potential side effects. In an open‑label study, 10 patients with active CD received 15 g TU‑100 per day for 8 consecutive weeks, and baseline anti‑inflammatory therapy was continued. The pre‑ and post‑treatment blood plasma levels of total ADM (t‑ADM) and mature‑ADM (m‑ADM) were determined using enzyme‑linked immunosorbent assays. The response of patients to the treatment was evaluated clinically using the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) score. The plasma levels of t‑ADM (16.4±1.1 vs. 20.2±1.7 fmol/ml, P=0.0218) and m‑ADM (1.7±0.1 vs. 2.2±0.1 fmol/ml, P=0.0284) increased following 8 weeks of TU‑100 treatment, compared with control. The IOIBD score of patients also improved, with a significant decrease in the score from 3.9±0.5 at 0 weeks to 2.4±0.4 at 8 weeks (P=0.0284). Out of the 10 components of the IOIBD scoring system, the scores for abdominal pain and tenderness, decreased significantly (P=0.014 and P=0.046). Therefore, TU‑100 was safe and well‑tolerated by the patients that participated in the current study. The present study determined that the pharmacologic action of TU‑100 is associated with changes in the circulating ADM levels and that treatment with TU‑100 may aid in the management of CD. These promising findings warrant further investigation in larger, multicenter studies.

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