Clematidis Radix (Wei Ling Xian in Chinese and Ireisen in Japanese) is a crude drug used in traditional Chinese medicine and is derived from the underground parts of Clematis plants, which belong to the family Ranunculaceae. The Clematidis Radix sold in modern markets is derived from a variety of botanical origins, whereas the Chinese and Japanese pharmacopoeias state that Clematidis Radix should be produced from Clematis hexapetala, C. mandshurica, or C. chinensis. To clarify the botanical origin of this crude drug, 9 closely related taxa of the genus Clematis growing in East Asia were subjected to molecular biological studies of their internal transcribed spacer (ITS) regions. We found that the ITS region nucleotide sequences of the 9 taxa had diverged. As a result, the 9 taxa could be successfully differentiated by comparing their whole ITS region sequences. Based on this result, 11 Clematidis Radix samples obtained from modern Japanese, Chinese, and Korean markets were genetically identified as follows: Of the samples from Japanese markets, 3 out of 4 were categorized as C. mandshurica, and one as C. chinensis. Among the samples from Chinese markets, 2 out of 4 were identified as C. mandshurica, and the other two as C. brachyura. Meanwhile, of the 3 samples from Korean markets, two were identified as C. mandshurica, and the other as C. terniflora var. robusta.

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Neurotrophic factor-like substances and inducers of neurotrophic factor biosynthesis have the clinical potential for serious neuronal diseases such as Alzheimer's disease (AD). Yokukansan (YKS) is a traditional Japanese herbal medicine consisting of seven medicinal herbs which has been used to treat anxiety disorder, insomnia, and the behavioral and psychological symptoms of dementia (BPSD) in Japan. In this study, we report the first investigation of the neurotrophic activity and mechanism of YKS in PC12 pheochromocytoma cells as a model of neuronal differentiation. YKS promoted neurite extension and increased the numbers of neurites in a dose dependent manner (0.1-1.0 mg/ml) similar to nerve growth factor (NGF) treatment. Our finding showed that YKS treatment significantly activated extracellular signal regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3K)/Akt, and inhibition of these kinases with the respective pharmacological inhibitors effectively attenuated YKS-induced neurite outgrowth in PC12 cells. We also found that addition of K-252a, a TrkA antagonist, significantly inhibited NGF- but not YKS-induced neurite outgrowth. These results indicate that YKS induces neurite outgrowth, at least in part, through the activation of ERK1/2 and PI3K/Akt-dependent but TrkA-independent pathways. We suggest that this neurotrophic activity of YKS is also neuroprotective and cause the amelioration of BPSD. Thus, these findings indicate that YKS might be useful as a pharmacological tool for only BPSD but also the cognitive disorder and as novel leading compound for drug development for AD.

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Atopic dermatitis is a representative intractable chronic eczematous skin disease. The symptoms of atopic dermatitis are eczema and an itching sensation, and this disease is caused by skin dysfunction and immune imbalance. Because the symptoms vary between individuals, several therapies are required for atopic dermatitis. Kampo medicines, traditional Japanese medicines, are used as an alternative medical option for the treatment of chronic allergic diseases such as rhinitis, asthma, and atopic dermatitis. Since Kampo medicines should be used according to the particular physical and mental conditions, the use of distinctive animal models is necessary for the experimental assessment of the efficacy of Kampo medicines. In this study, Kampo medicines were assessed for their anti-itching effect and with respect to the cure and prophylaxis of pruritus by single or serial oral administration to 2 types of atopic dermatitis-like pruritus models. We assessed 7 kinds of Kampo medicines that have been used for atopic dermatitis patients. In 7 Kampo medicines, only shofusan (SFS) had an instant effect —even on using a single dose —on scratching behavior induced by multiple treatments with 2,4,6-trinitrochlorobenzene (TNCB) for 4 weeks in NC mice; it ameliorated chronic itching on oral administration for 11 d, by preventing mast cell differentiation and degranulation. In the other model using BALB/c mice painted with TNCB repeatedly, another Kampo medicine, hochuekkito (HET) inhibited the induction of scratching behavior. The results indicate that certain Kampo medicines such as SFS and HET may improve chronic itching sensation in atopic dermatitis to the same extent as or better than existing antiallergic medicines.

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The number of patients with inflammatory diseases such as rheumatoid arthritis, osteoarthritis and lumbar spondylosis is increasing in Japan. The overexpression of NO, COX-2, and some cytokines has been found in the affected areas of these patients, which suggests that reducing inflammatory mediator levels may be therapeutically effective. Atractylodis Lanceae Rhizoma (AL) is one of the Kampo herbs that exhibits an anti-inflammatory effect, and has been included in some Kampo formulas used to cure articular rheumatism and other rheumatic diseases. In this study, we examined the inhibitory effect of a 70% methanol extract of AL and the compounds isolated from the extract on LPS-stimulated RAW264, a mouse macrophage cell line. The extract reduced NO production and inhibited mRNA expression of the inflammation-related factors COX-2, IL-1β, IL-6, and TNF-α. We isolated hinesol, β-eudesmol and acetylatractylodinol from the extract, and revealed that hinesol and acetylatractylodinol were effective in reducing NO production and the levels of inflammation related mRNAs, respectively. Hinesol and acetylatractylodinol are characteristic essential oil constituent of AL and these compounds play a specific aroma of AL. High contents of hinesol sometimes appear as flocculent crystals with β-eudesmol on the surface of crude drugs, which empirically indicate the high quality of these drugs. Our results may help to explain the traditional way to examine the quality of a crude drug.

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Background: Kampo medicine has been shown to be useful for reducing the adverse effects of pegylated interferon (PEG-IFN) α-2b plus ribavirin (RBV). The study was done to determine if Kampo would have a synergistic effect with PEG-IFNα-2b plus RBV that would improve their effectiveness in the treatment of chronic hepatitis C.
Methods: From a total of 51 chronic hepatitis C virus (HCV) patients, 26 received PEG-IFNα-2b plus RBV treatment combined with Kampo medicine (group A) and 25 received only the standard treatment (group B). Group B patients were prescribed a mixture of shimbuto and ninjinto extract to be taken three times a day before meals.
Results: The early virological response (EVR) and sustained virological response (SVR) rates were significantly higher in group A than in group B (EVR: 84.6%, 22 of 26 vs 56.0%, 14 of 25, P=0.034: SVR: 76.9%, 20 of 26 vs 48.0%, 12 of 25, P=0.033). 22 of 26 patients in group A (84.6%) and 18 of 25 patients in group B (72.0%) received at least the minimum acceptable dosage (at least 80% or more of the target PEG-IFNα-2b and 60% or more of RBV) during treatment, with no significant between group difference in the rate of SVR.
The discontinuation rate was significantly lower in group A, in which no patients discontinued, than in group B (20.0%, 5 of 25) (P=0.023).
Conclusions: A mixture of shimbuto and ninjinto reduced the discontinuation rate and improved the treatment efficacy of patients with chronic HCV treated with PEG-IFNα-2b plus RBV.

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A screening of extracts from seven Lamiaceae plants for their effects on xanthine oxidase, a key enzyme in the biosynthesis of uric acid, was performed. Among the plants tested, peppermint (dried leaves of Mentha piperita) showed the potent inhibitory activity. Inhibitory activity guided purification of the active constituent led us to obtain pratensein and apigenin. This is the first report on the inhibitory activity of pratensein on xanthine oxidase.

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