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Active ingredients of traditional Japanese (kampo) medicine, inchinkoto, in murine concanavalin A-induced hepatitis

Mase, Akihito, Makino, Bunsho, Tsuchiya, Naoko, Yamamoto, Masahiro, Kase, Yoshio, Takeda, Shuuichi, Hasegawa, Takaaki
Journal of ethnopharmacology 2010 v.127 no.3 pp. 742-749
herbal medicines, Oriental traditional medicine, medicinal plants, hepatitis, concanavalin A, mice, animal models, mechanism of action, hepatoprotective effect, interferons, interleukin-12, active ingredients, phytochemicals, plant extracts, fractionation, liver, biomarkers, cytokines, blood chemistry, splenocytes, macrophages, in vitro studies, oral administration
Aim of the study: The traditional Japanese (kampo) medicine inchinkoto (ICKT) is used in Eastern Asia as a choleretic and hepatoprotective agent. Previously, we reported that ICKT ameliorates murine concanavalin A (con A)-induced hepatitis via suppression of interferon (IFN)-γ and interleukin (IL)-12 production. In the present study, we investigated the active ingredients of ICKT. Materials and methods: ICKT and extracts of its component herbs were fractionated, and their effects on liver injury and cytokine production in vivo (biochemical markers of liver injury and cytokine levels in serum) and in vitro (cytokine and nitrite production in the cultures of splenocytes and peritoneal macrophages). Results: Decoctions of component herbs, Artemisiae Capillari Spica (Artemisia capillaris Thunberg: ‘Inchinko' in Japanese), Gardeniae Fructus (Gardenia jasminoides Ellis: ‘Sanshishi') and Rhei Rhizoma (Rheum palmatum Linné: ‘Daio') were administered orally. Inchinko and Sanshishi decreased serum transaminases and IFN-γ concentrations. Examination of fractions of component herbs suggested that capillarisin, a component of Inchinko, has potent hepatoprotective activity in vivo. In in vitro studies, capillarisin and genipin, an intestinal metabolite of geniposide that is contained in Sanshishi, were examined. IFN-γ production was significantly suppressed by capillarisin and genipin in con A-stimulated splenocyte culture. Genipin also suppressed IL-1β, IL-6, and IL-12p70 synthesis. Capillarisin and genipin decreased nitrite release from IFN-γ-stimulated macrophages. Conclusions: These results suggested that both Inchinko and Sanshishi may contribute to the protective effects of ICKT against con A hepatitis. Capillarisin was found to be potently hepatoprotective, and genipin may also contribute, especially via modulation of cytokine production.