Publications by authors named "Yoshifumi Irie"

Aim: To evaluate the role of intestinal microflora in the effects of multi-herbal medicine on gene expression in the gut and liver.

Methods: The multi-herbal medicine Juzentaihoto (JTX) was administered to five germ-free mice and regular mice for 2 wk. Among the results of the comprehensive gene chip analysis of the intestine and liver, we featured heat shock proteins (HSPs) 70 and 105 because their gene expression changed only in the presence of microflora.

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Parkinson's disease (PD) is a neurodegenerative disease of the brain characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN). No clinically proven drugs that may halt or retard the progression of PD have been reported. This study examined the anti-PD effect of a traditional Japanese/Chinese herbal remedy Toki-to (TKT) using mice treated with a neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP).

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Juzen-taiho-to (JTX), one of the commonly prescribed traditional Japanese herbal medicines (Kampo), is indicated for adjunctive treatment of cancers and autoimmune diseases. To understand the mechanisms underlying the clinical effects of JTX, the effects of orally administered JTX on the expression of metallothioneins (MTs) were examined in the liver, spleen, small and large intestines of mice. In addition, the expression of MTs in specific pathogen free (SPF) mice was examined to understand the participation of intestinal bacteria in the expression of MTs.

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Eugenol (1) is an active principle of Rhizoma acori graminei, a medicinal herb used in Asia for the treatment of symptoms reminiscent of Alzheimer's disease (AD). It has been shown to protect neuronal cells from the cytotoxic effect of amyloid beta peptides (Abetas) in cell cultures and exhibit antidepressant-like activity in mice. Results from this study show that eugenol inhibits monoamine oxidase A (MAOA) preferentially with a K(i)=26 microM.

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Here we show that eugenol has an antidepressant-like activity comparable to that of imipramine using a forced swim test and a tail suspension test in mice. Furthermore, we show that both eugenol and imipramine induce brain-derived neurotrophic factor (BDNF) in the hippocampus with and without induction of metallothionein-III (MT-III), respectively. It may be possible that MT-III expression is involved in the exhibition of antidepressant-like activity of eugenol, not of imipramine.

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Metallothioneins (MTs) are metal-binding proteins that are expressed in many tissues including brain. MTs protect cells and organs against metal toxicity and oxidants. Among MTs, a brain-predominant subtype MT-III has prominent neuroprotective activity against various types of damage.

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Effect of Choto-san (TJ-47), a Kampo medicine, on impairment of learning performance was evaluated by means of a step-through passive avoidance task in SAMP8 mice, a senescence-prone substrain. Tokishakuyaku-san (TJ-23), another Kampo medicine, was also employed for comparison. SAMP8 mice at the age of 10-12 months showed a poorer passive avoidance response than SAMR1 mice, a senescence-resistant substrain, in the memory-retention test, but not in the memory-acquisition test.

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The effects of water extracts of six medicinal herbs (Radix polygalae tenuifoliae, Radix salviae miltiorrhizae, Rhizoma acori graminei, Rhizoma pinelliae ternatae, Tuber curcumae and Scletrotium poriae cocos) on the cytotoxic action of Abeta(1-40) were tested with PC-12 cells. Only the extract of R. acori graminei (RAG) significantly decreased Abeta(1-40)-induced cell death.

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Recent studies have shown that metallothionein-III (MT-III), but not MT-I or -II, antagonizes both the neurotrophic and neurotoxic effects of amyloid beta peptides (Abetas). Further, its anti-Abeta-toxicity effect was attributed to the fact that it inhibits the formation of fibrillar Abeta. MT-III alone also affects neuron survival in culture-promoting at low but inhibiting at high concentrations.

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Metallothionein (MT) is a two-domain protein with zinc thiolate clusters that bind and release zinc depending on the redox states of the sulfur ligands. Since S-nitrosylation of cysteine is considered a prototypic cellular redox signaling mechanism, we here investigate the reactions of S-nitrosothiols with different isoforms of MT. MT-III is significantly more reactive than MT-I/II toward S-nitrosothiols, whereas the reactivity of all three isoforms toward reactive oxygen species is comparable.

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