Abstract
BackgroundThe traditional Japanese medicine juzentaihoto (JTX) is a pharmaceutical grade multi-herbal medicine widely used for the prevention of cancer metastasis and infection in immuno-compromized patients in Japan. The effect of JTX has been supposed to be intimately affected by the immunological properties of host and enteric microflora. The influence of JTX on the gene expression profile in the large and small intestines was investigated by microarray analyses using mice of different strains with or without enteric microflora.ResultsIn all types of mice, including germfree (GF) animals, the genes most affected by two-week oral JTX treatment were the type 1 interferon (IFN)-related genes including Stat1, Isgf3g and Irf7, which play a critical role in the feedback loop of IFN-α production cascade. In IQI specific pathogen free (SPF) mice JTX increased the steady state level of the expression of IFN-related genes, but had the opposite effect in IQI GF and BALB/c SPF mice. Promoter analysis suggests that tandem repeated $IRFF (the promoter sequences for interferon regulatory factors) may be a primary target for JTX action. Pre-treatment of JTX accelerated the effects of an oral IFN "inducer" 2-amino-5-bromo-6-methyl-4-pyrimidinol (ABMP) (up-regulation of IFN-α production in IQI strain and down-regulation in BALB/c mice), which is in good accordance with the effect of JTX on gene expression of type 1 IFN-related genes.ConclusionsMicroarray analysis revealed that the target of JTX might be the transcription machinery regulating the steady-state level of genes involved in the ISGF3-IRF7 cascade, whose effect is bi-directional in a strain- and microbiota-dependent manner.
Highlights
The traditional Japanese medicine juzentaihoto (JTX) is a pharmaceutical grade multi-herbal medicine widely used for the prevention of cancer metastasis and infection in immuno-compromized patients in Japan
Literature analysis of GeneChip data Firstly, we investigated the effect of JTX on the steady state level of mRNA in the large intestines using IQI specific pathogen free (SPF) and Balb/c SPF mice (Experiment 1)
When we applied the criteria described in Materials and Methods (p < 0.1, fold change > 1.5 or < 0.67), there were 27 and 16 annotated/identified genes whose expression level was increased by JTX treatment in IQI and Balb/c mice, respectively ("SPFLI-up” and “BALBLI-up” lists in Table 1 and Additional File 1, respectively)
Summary
The traditional Japanese medicine juzentaihoto (JTX) is a pharmaceutical grade multi-herbal medicine widely used for the prevention of cancer metastasis and infection in immuno-compromized patients in Japan. In Japan, certain traditional herbal medicines (Kampo medicines), which comprise hot water extracts from a mixture of medicinal plants, have been widely used as ethical drugs and become integrated into the modern medical system [1,2,3,4]. Experimental studies show that JTX reduces the side effect of chemotherapy and radiotherapy [13,14,15,16,17], prevents various types of cancer and its metastasis [18,19,20,21,22,23,24], improves osteoporosis [25,26] as well as atopic dermatitis [1], and protects against Candida infection [19,27]. The active substances responsible for stimulation of hematopoietic stem cell growth [28,29], various immunostimulating activities [28,30,31,32,33,34], alleviation of side-effects by chemotherapeutic agents [32,35], and protection against Candida infection [36] have been identified
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