Search

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. [Copyright &y& Elsevier]

Abstract: Aim of study: Luteinizing hormone-releasing hormone (LH-RH) has been suggested as an inducer of centrally mediated elevation of skin temperature, and calcitonin gene-related peptide (CGRP) is one of the potent vasodilator neuropeptides that has been suggested as an inducer of peripherally mediated elevation of skin temperature. We investigate the effect of the Japanese herbal medicine Tokaku-jyoki-to using two rat-models for menopausal hot flash. Materials and methods: Tokaku-jyoki-to used in present study was prepared as a spray-dried powder from hot-water extract. Skin temperature was measured by thermister thermometer. Estrogen receptor (ER) binding assay of Tokaku-jyoki-to extract was performed using human recombinant ERα or ERβ. Results: Oral Tokaku-jyoki-to (1000mg/kg) restored skin temperature rise induced by LH-RH or CGRP in ovariectomized (OVX) rats as well as subcutaneous 17β-estradiol (0.010mg/kg) did. Tokaku-jyoki-to did not affect the lower concentration of plasma estradiol and the decreased uterine weight due to ovariectomy, although the hormone replacement of 17β-estradiol restored them. In estrogen receptor ligand-binding study, Tokaku-jyoki-to extract bound to human ERα poorly and did not bound to human ERβ. Conclusions: These results suggest that Tokaku-jyoki-to, which appears to contain organ-specific selective estrogen receptor modulator, may be useful for the treatment of hot flashes in patients for whom estrogen replacement therapy is contraindicated as well as menopausal women. [Copyright &y& Elsevier]