b-e: Gene expression of Stat1, Stat2, Isgf3g, which compose an ISGF3 complex, and Irf7. expression data. (a) Gene chip data of all the probe sets whose MAS calls are “present” for all triplicate samples (a) and RT-PCR data of selected genes (b) were log-transformed and subjected to heat map generation. 1471-2164-13-30-S8.DOC (953K) GUID:?21D7DC71-1657-41D0-ADCC-D9C3F1980337 Abstract Background 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. 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. Results In 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- 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- 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. Conclusions Microarray 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. Background In Japan, certain traditional herbal medicines (Kampo medicines), which comprise hot water extracts AZ191 from a mixture of medicinal plants, have been widely used as ethical drugs and become integrated into the modern medical system [1-4]. These traditional medicines are manufactured under strict scientific quality control and are covered by public health insurance. A large amount of clinical and basic research on Kampo medicines has been performed, including more than 10 multicenter, placebo-controlled, double-blind studies. We investigated the effects of Juzentaihoto (JTX) in this study. JTX is a well known Kampo medicine that comprises 10 different herbs; em Ginseng radix /em , em Astragali radix /em , em Angelicae radix /em , em Rehmanniae radix /em , em Atractylodis lanceae rhizoma /em , em Cinnamomi cortex /em , em Poria /em , em Paeoniae radix /em , em Ligustici rhizoma /em and em Glycyrrhizae radix /em . JTX has been used for centuries for the treatment of various kinds of disease or disorders such as anemia, rheumatoid arthritis, atopic dermatitis, chronic fatigue syndrome and ulcerative colitis [5-12]. Experimental studies show that JTX reduces the side effect of chemotherapy and radiotherapy [13-17], prevents various types of cancer and its metastasis [18-24], improves osteoporosis [25,26] as well as atopic dermatitis [1], and protects against Candida infection [19,27]. The active AZ191 substances responsible for stimulation of hematopoietic stem cell growth [28,29], various immunostimulating activities [28,30-34], alleviation of side-effects by chemotherapeutic agents [32,35], and protection against Candida infection [36] have been identified. In Kampo therapy, medical care is individualized with tailoring prescriptions depending on the patients’ constitution, disease state and responsiveness to therapy [2,37,38]. Indeed, the therapeutic effects of Kampo-medicines have been Rabbit polyclonal to ACSS3 known to vary markedly among individuals. Therefore, depending on the individual patient it AZ191 is not unusual to use different Kampo drugs to treat the same disease, or alternatively, to use the same drug to treat apparently different diseases. Thus, the effect of Kampo medicines should be investigated by taking into consideration the possible dependence on the constitution, for example the immunological properties, of the individual patient. Most Kampo medicines administered orally are known to have probiotic, prebiotic and antibiotic properties. For example, we have previously demonstrated that JTX alters the population of intestinal microflora, which affects the gene expression of heat shock proteins hsp70 and hsp110 in the gut and liver (Kampo affects microflora) [39]. Conversely, certain glycosides included in Kampo medicines are known to require metabolic conversion to a bioactive deglycosylated form by intestinal flora for expression of their pharmacological activity (Microflora affects Kampo) [2]. Finally, certain immunomodulating effects of Kampo medicines, including JTX, are known to be mediated by chemical components that are not thought to be absorbed [33,36,40]. The components of Kampo medicines may affect general immunity indirectly, presumably through interaction with the gut local immune system. Thus,.
