The present article introduces our study related to the neuroactive and neuroprotective effects of Tokishakuyakusan (TSS) on animal model of Alzheimers disease (AD) or cerebrovascular dementia. Single administration of TSS ameliorates the impairment of spatial memory induced by scopolamine in radial maze test and enhances tremors induced by oxotremorine, a muscarinic M1 receptor agonist. We found that Ang-S-1, which is a partial inverse agonist of benzodiazepine, was an active compound of TSS in improving effect on impairment of spatial memory in radial maze test. We also found that single administration of TSS increased both acetylcholine (ACh) release and blood flow in the dorsal hippocampus, and TSS protected against neurotoxicity induced by amyloid β protein (Aβ). In animal model of AD or cerebrovascular dementia, we found that TSS prevented the impairment of spatial memory, neuronal death and TUNEL positive cells induced by repeated ischemia, and TSS prevented the impairment of spatial memory and decrease of ACh release induced by ovariectomized combined with Aβ. The present findings show that TSS prevents the memory deficits through not only enhancing ACh release but also protecting neuronal damage. Thus, TSS exhibits the neuroactive and neuroprotective effects in animal model of AD or cerebrovascular dementia, and therefore may be useful in the treatment of these dementia.

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The suppressive effects of the traditional herbal medicines Hachimijiogan (TJ-7; Pa-Wei-Ti-Huang-Wan in Chinese) and Ninjin'yoeito (TJ-108; Ren-Shen-Yang-Rong-Tang in Chinese) on the reversion of attenuated polio vaccine viruses to the neurovirulent genotype were analyzed for the purpose of controlling vaccine-associated paralytic poliomyelitis (VAPP) and epidemics caused by the virulent vaccine-derived poliovirus (VDPV). Proliferations of the cells and viruses were not inhibitory as long as the medicines were used in optimum concentrations (TJ-7; 0.25mg/mL, TJ-108; 0.5mg/mL). As a result of analyzing accumulations of reversions of the specific bases on the virus genome related to neurovirulence in monkeys, it was demonstrated that TJ-108 suppressed the reversion of type 1 and 3 polio vaccine viruses to the neurovirulent genotype in cultured cells which were derived from the human alimentary tract. However, no suppressive effect on the reversion by TJ-7 was observed. Although verification of the suppressive effect of TJ-108 on reversion in the human alimentary tract is necessary, it is expected that TJ-108 will contribute to resolving the VAPP and VDPV problems and to the achievement of the poliomyelitis eradication program of the World Health Organization.

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This study was undertaken to investigate the hepatoprotective activity of Eclipta prostrata L_INN. (EP) in ethanol induced rat hepatic injury. In the in vitro study, EP (0.1, 0.2, 0.3 mg/ml) increased % MTT reduction and decreased the release of transaminases (ALT and/or AST) in rat primary cultured hepatocytes being treated with ethanol. Hepatotoxic markers studied in rats included serum transaminases (ALT and AST), serum triglyceride (STG), hepatic triglyceride (HTG), TNF-α and IL-1β together with histopathological examination. Pretreatment of rats with EP at oral dose of 10, 20, 30 mg/kg and silymarin (a reference hepatoprotective agent) at 5 mg/kg 4 h before ethanol (5 g/kg, p.o.) decreased the ethanol induced levels of ALT and/or AST. The 30 mg/kg EP dose gave the best result similar to SL. Treatment of rats with EP (30 mg/kg/day) or SL (5 mg/kg/day) for 7 days after 21 days with ethanol (4 g/kg/day, p.o.) enhanced liver cell recovery by bringing the levels of ALT, AST and IL-1β back to normal. Histopathological observations confirmed the beneficial roles of EP and SL against ethanol induced liver injury in rats. Possible mechanism may involve their antioxidant activity.

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We previously demonstrated that the motility of highly metastatic murine osteosarcoma cells is significantly reduced by serum from a mouse after intake of maoto and that spontaneous metastasis in tumor-bearing mice is suppressed by oral administration of maoto. Since it is important to evaluate the efficacy of maoto against human metastatic tumors, we investigated the inhibitory effect of maoto on human serum (HS)-induced motility of a human breast cancer cell line, MDA-MB-231. To determine an efficient concentration of HS to induce cell motility, we tested several concentrations of human serum. Motility was induced by HS in a concentration-dependent manner and reached a plateau at 1%. Therefore, the concentration of HS adequate for a serum-induced cell motility assay was determined to be 1%. We investigated the effect of maoto, juzentaihoto, or shikunshito on HS-induced cell motility using the assay. Cell motility was reduced by the addition of maoto in a concentration-dependent manner; 100 μg/ml of maoto caused an 83% reduction of cell motility. In contrast, no significant changes were observed following the addition of juzentaihoto or shikunshito. Maoto had no effect on the cell growth at the concentration of 6.25 to 100 μg/ml, indicating that maoto suppressed HS-induced motility without cytotoxicity. These results indicate that maoto suppresses not only murine cancer cell motility but also human cancer cell motility and suggest that maoto will be important for clinical application for the prevention of cancer metastasis.

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Atopic dermatitis (AD) is a chronic inflammatory skin disorder with pruritic and eczematous lesions. AD is characterized by the predominant infiltration of Th2-type cells in the acute phase of skin lesions. Thymus and activation-regulated chemokine (TARC), a member of the CC chemokine superfamily was identified as a selective chemoattractant for Th2-type cells. The serum TARC level is significantly increased in patients with AD and is correlated with the severity of AD. Keishibukuryogan (KBG) is a Kampo formula composed of five kind of crude drugs and has been administered to patients with blood stagnation in Japan. This study investigated the effect of KBG on disease activity and TARC production in AD patients. AD patients were administered KBG for 4 to 6 weeks in addition to their prescribed medications. The SCORAD index and VAS score were decreased by the administration of KBG. The serum TARC level of the AD patients was much higher than that of normal controls. This elevated serum TARC level was significantly decreased by administration of KBG. These results suggest that KBG may improve AD by the inhibitory effect on Th2-type chemokine production.

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