Abstract

In this study, we first measured some cytokine concentrations in the serum of patients treated with Juzentaihoto (JTT). Of the cytokines measured interleukin (IL) -18 was the most prominently up-regulated cytokine in the serum of patients under long term JTT administration. We next evaluated the effects of JTT in mice, focusing especially on natural killer T (NKT) cell induction. Mice fed JTT were compared to control group ones. After sacrifice, the liver was fixed, embedded and stained. Transmission electron microscope (TEM) observations were performed. Although the mice receiving the herbal medicine had same appearance, their livers were infiltrated with massive mononuclear cells, some of which were aggregated to form clusters. Immunohistochemical staining revealed that there was abundant cytokine expression of IL-12 and IL-18 in the liver of JTT treated mice. To clarify what the key molecules that induce immunological restoration with JTT might be, we next examined in vitro lymphocyte cultures. Mononuclear cells isolated and prepared from healthy volunteers were cultured with and without JTT. Within 24 hours, JTT induced the IL-12 and IL-18 production and later (72 hours) induction of interferon (IFN)-gamma. Oral administration of JTT may induce the expression of IL-12 in the early stage, and IL-18 in the chronic stage, followed by NKT induction. Their activation, following immunological restoration could contribute to anti-tumor effects.

Highlights

  • Before the modern use of synthetic drugs, many medicines worldwide were derived from natural plant sources, including the nuts, roots and leaves

  • Serum from patients treated with JTT medicine showed no changes in the concentration of several serum cytokines (IL-1, IL-2, IL-4, IL-6, IL-12, TNF-α, IFN-γ, data not shown)

  • These cytokines were undetectable by the enzyme linked immunosorbent assay (ELISA) in this study

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Summary

Introduction

Before the modern use of synthetic drugs, many medicines worldwide were derived from natural plant sources, including the nuts, roots and leaves. In Asian countries, especially in ancient China, many botanical materials had been adapted into medicines and these compositions have been described in old medicical encyclopedias. Kampo originally means “Chinese style”, in medicine, and for other Japanese words describing life styles. Kampo these days has come to mean “ethnical traditional medicine”. The principles of Kampo drugs were originally based on old Chinese traditional medicines and comprise about one hundred and fifty kinds of compositions of natural herbs and other natural products. Kampo medicine is generally characterized by its low frequency of severe adverse effects and is used in current clinical practice all over Japan and other countries

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