Anti-inflammatory effect of hospital-grade hochuekkito extract, a traditional Japanese herbal medicine, on methotrexate-induced intestinal mucositis in mice

ABSTRACT Aim Hospital‐grade extract of hochuekkito, a traditional J apanese herbal ( K ampo) 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 ( C yld ) 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 C yld, 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.