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

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.

Anti‐Inflammatory Effects of PEGylated Human Adrenomedullin in a Mouse DSS‐Induced Colitis Model

“…Furthermore, in a clinical study, continuous intravenous infusion of hAM ameliorated the symptoms of intractable UC without adverse side effects [Ashizuka et al ]. Moreover, a traditional Japanese medicine (Daikenchuto) increases circulating hAM levels and aids in healing Crohn's disease [Kominato et al, ]. As we described above, the anti‐inflammatory properties of hAM make it an effective candidate therapeutic agent for the treatment of IBD.…”

The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial

“…ADM has various bioactivation functions, including a hypotensive effect by vasodilation and roles in cell migration, differential regulation, anti-inflammation, and increasing vascular flow. Research using rodents revealed that ADM is induced by TJ-100 administration, and that TJ-100 has many effects, e.g., accelerating gastrointestinal transit and increasing intestinal blood flow, and an anti-inflammation effect [ 17 ]. The concentration of ADM in human blood plasma has not been established.…”

Recent Advances in Herbal Medicines for Digestive System Malignancies

“…Daikenchuto (TJ-100) is a traditional herbal medicine, also called Kampo, composed of Capsicum Annuum , dried ginger, ginseng and cerealose (Endo et al, 2017 ) and can be used for gastrointestinal diseases including intestinal obstruction and Crohn's disease (Kominato et al, 2016 ; Okada et al, 2016 ). Some studies found that TJ-100 can suppress tumor development and alleviate side effects of surgery (Yoshikawa et al, 2015 ; Nagata et al, 2016 ; Hasebe and Matsukawa, 2017 ).…”