Anti‐inflammatory effect of hospital‐grade hochuekkito extract, a traditional Japanese herbal medicine, on methotrexate‐induced intestinal mucositis in mice. Issue 2 (25th July 2015)

• Record Type: Journal Article
• Authors: Sekiya, Michiko; Kiyohara, Hiroaki; Maruyama, Hiroko; Tsukada, Naoya; Yasuda, Ayano; Nagai, Takayuki; Yamada, Haruki
• Is Part Of: Traditional & Kampo Medicine. Volume 2:Issue 2(2015)
• Page Start: 81
• Page End: 88
• Publication Date: 2015-07-25
• Subjects: hochuekkito -- hospital‐grade extract -- interleukin‐1 receptor‐associated kinase‐M -- intestinal mucositis -- methotrexate -- regulatory adaptor molecule; Medicine, Oriental -- Japan -- Periodicals; Medicine, Chinese -- Japan -- Periodicals; Medicine, East Asian Traditional; Japan; Medicine, Chinese; Medicine, Oriental; Japan; Electronic journals; Periodicals; Periodicals; 615
• DOI: 10.1002/tkm2.1026
• Languages: English
• ISSNs: 2053-4515

Abstract

ABSTRACT: Aim: Hospital‐grade extract of hochuekkito, a traditional Japanese herbal (Kampo) formula, has been found to be clinically effective against mucositis induced by anticancer drugs, but the mechanism of action of this formula has not been clarified as yet. The aim of this study was to investigate the anti‐inflammatory effects of hochuekkito against chemotherapy‐induced mucositis in a mice model. Methods: Mucositis in jejunum was induced by i.p. injection with methotrexate (MTX, 100 mg/kg) in BALB/c mice. Hospital‐grade hochuekkito extract (TJ‐41) was administered in oral doses (1 g/kg/day). Results: The tissue damage score of jejunum was improved in early stage mucositis (at day 3 after one‐off MTX injection). Expression of tumor necrosis factor ( TNF )‐α and interleukin‐1 β mRNA in jejunum of MTX‐treated mice was downregulated by TJ‐4 at day 2 and 3 after one‐off MTX injection. mRNA expression of regulatory adaptor molecules such as interleukin‐1 receptor‐associated kinase‐3 ( IRAK‐M ), single immunoglobulin and toll‐interleukin 1 receptor domain ( SIGIRR ), tumor necrosis factor‐α‐induced protein 3 ( A20 ) and cylindromatosis ( Cyld ) was significantly enhanced at day 1 of oral TJ‐41 treatment, but these changes were not observed on MTX treatment alone. Conclusions: TJ‐41 reduces intestinal mucositis induced by MTX. TJ‐41 induces specific expression of regulatory adaptor molecules, such as IRAK‐M, SIGIRR, A20 and Cyld, in the MyD88‐associated inflammatory signal cascade under conditions of inflammation, and this phenomenon is postulated to be associated with the anti‐inflammatory effect of the formula on intestinal mucositis.