We recently reported that the herbal medicine (Maoto) might have immunomodulatory effects when used in conjunction with IFN-β. In order to examine the relation between host immune reaction and virological effects upon treatment with Maoto and IFN-β, we monitored the changes in lymphocyte populations of peripheral blood by flow-cytometry. Twenty-five patients with chronic hepatitis C were enrolled in this study. They received a daily dose of 6 million units of IFN-β for 8 weeks. Maoto was given orally 4 times a day during the IFN-β administration, and we monitored the changes in lymphocyte populations of peripheral blood by flow-cytometry. Six patients were sustained virological responders (SR), 10 were transient responders (TR), and 9 were nonresponders (NR). The percentage of CD16⁺CD56⁺ lymphocyte populations was decreased in all groups between pretreatment and 4 weeks, but it was significantly increased in SR compared with TR and NR between 4 and 8 weeks. The percentage of HLADR⁺CD8⁺ lymphocyte populations was significantly increased in SR and TR compared with NR between pretreatment and 8 weeks. Our results suggested that monitoring of changes in peripheral CD16⁺CD56⁺ and HLADR⁺CD8⁺lymphocyte populations could be useful to treat chronic hepatitis C with the combination therapy of Maoto and IFN-β.

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In the present study we examined the anti-atherosclerotic effect of Saikokaryukotsuboreito (SRB), one of the traditional Chinese herbal medicines, which is used for the treatment of atherosclerosis, and hypertension in addition to various neurological disorders. SRB, which was dissolved in the daily intake of drinking water at a concentration of 10 times the daily human dose (1.01 g/kg/d), was given to apoE-deficient mice from the day on the atherogenic diet for 13 weeks. Feeding them a cholesterol-enriched diet for 13 weeks induced a striking hypercholesterolemia, and atherosclerosis in control apoE-deficient mice. On the other hand, treatment with SRB exhibited no effect on body weight, serum total cholesterol, and lipoprotein profile, whereas the atherosclerotic lesions were significantly reduced throughout the aorta, especially in the sinus and aortic arch compared with control mice. These results may reveal that SRB is able to suppress the development of atherosclerosis without anti-hypercholesterolemic effect and further is a potential therapeutic agent to treat or prevent atherosclerosis.

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Cure of cognitive disorders such as amnesia, attention deficit and Alzheimer's disease is still a nightmare in the field of medicine. Nootropic agents such as piracetam, aniracetam and choline esterase inhibitors like Donepezil^® are being used for improving memory, mood and behavior, but the resulting side effects associated with these agents have made their applicability limited. Oxygen free radical, the harmful byproduct of oxidative metabolism is known to cause organic damage of living system. They are implicated in various pathological events such as mutagenesis, ageing and neurodegenerative disorder. Indian system of medicine emphasizes use of herbs, and nutraceuticals or life style changes for controlling age related neurodegenerative disorders.
In the present study, the effect of isolated piperine from Piper nigrum fruits on memory and behavior mediated via monoamine neurotransmitters was investigated. Elevated plus maze and passive avoidance paradigms were used as exteroceptive behavioral models, where as scopolamine induced amnesia was the interoceptive behavioral model. The effects on lithium induced head twitches, clonidine-induced hypothermia, and halperidol-induced catalepsy were also observed to study the effect on serotonin, noradrenaline and dopamine mediated behavior, respectively. Piperine isolated from P. nigrum exhibited prominent nootropic activity, reversed clonidine-induced hypothermia, decreased lithium induced head twitches and significantly delayed haloperidol induced catalepsy at a dose of 10 mg/kg. The alkaloid modified 5-HT and NA mediated behavior. Hence, piperine from the fruits of P. nigrum can be employed as a potential nootropic agent.

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We used a guinea-pig model of long-term exposure to cigarette-smoke to examine the antitussive effect of Bakumondoto (Mai-Men-Dong-Tang, TJ-29) on intractable coughs caused mainly by chronic smoking. The total number of coughs induced by capsaicin inhalation was significantly increased in guinea-pigs that had been exposed to mainstream cigarette smoke compared to that in naive guinea-pigs that had been exposed to fresh air. The antitussive effect of dihydrocodeine (10 mg/kg, p.o.) on the induced cough reflex was significantly attenuated in mainstream cigarette smoke-exposed guinea-pigs. On the other hand, the antitussive effect of TJ-29 (1 g/kg, p.o.) brought this level to the same as that in fresh air-exposed naive guinea-pigs. Nitric oxide (NO) metabolites in bronchoalveolar lavage fluid were markedly and significantly increased in mainstream cigarette smoke-exposed guinea-pigs compared to fresh air-exposed naive guinea-pigs. Furthermore, treatment with TJ-29 reduced these increased NO metabolites to the same levels as those in naive guinea-pigs that had been exposed to fresh air. These findings suggest that augmented NO release is associated with increased cough sensitivity as a result of mainstream cigarette smoke exposure. Furthermore, we can speculate that the antitussive effect of TJ-29 might be, at least in part, mediated by the inhibition of synthesis or release of NO.

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A simple and rapid method for determination of Aconitum alkaloids, aconitine, mesaconitine, hypaconitine and jesaconitine, in serum and urine samples has been developed using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) combined with Extrelut^® column extraction. The protonated molecular ions were observed as base peaks of these alkaloids. The alkaloids were separated on an XTerra^® RP18 column with isocratic elution with a solvent mixture of 0.1% (v/v) formic acid in acetonitrile and 0.1% (v/v) formic acid in aqueous solution (24:76, v/v) using selective ion monitoring of protonated molecular ions. The calibration curves of the alkaloids in serum and urine were linear in the range of 5-200 pg per injection, and the detection limits of the alkaloids were 1 pg per injection (S/N=3). The recovery rates of the alkaloids ranged from 83.7% to 89.0% in serum and from 85.6% to 89.9% in urine. The inter-day precision and intra-day precision were acceptable. This method of analysis can be used for identification and quantitative determination of Aconitum alkaloids in cases of aconite poisoning and will be useful for investigating the pharmacokinetics of aconite substances in humans. In addition, it is simple and rapid and should therefore be useful in emergency medicine, in which quick and accurate test results are required.

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Hangeshashinto (HST) has been used as an herbal formula to treat inflammatory ulcerative gut diseases complicated with psychoneurosis in Japanese traditional Kampo medicine. In our previous study, we revealed that HST improved rat inflammatory colitic symptoms induced by the intracolonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The aim of the present study is to clarify the anxiolytic effect of HST in the same model. The anxiety-like behavior was measured using an elevated plus maze (EPM). TNBS-treatment reduced the exploring time spent on the open arms of EPM, suggesting that as anxiety-like behavior was observed. This behavior was significantly improved by daily oral administration of HST. To identify the active constituents for this anxiolytic effect, berberine (BE), baicalin (BA), glycyrrhizin (GL) or saponin fraction of ginsenosides (GS), or their combinations were tested. Oral treatment with these four constituents significantly ameliorated the exploration time spent on open arms, although no effects were found in the treatment with each of BA, BE, GL or GS. Among the combinations in these 4 constituents, the combination of BA and BE exerted the anxiolytic effect, however, the combination of GL and GS, which is the active combination to improve colitic symptoms (damage score, colonic wet weight and ulcerative area) in our previous study (Kawashima et al. Biol. Pharm. Bull. 27, 1599, 2004), did not show any improvement. These results suggest that HST would have anxiolytic effect, which would be partially derived from the combination of BA and BE, and HST ameliorated the colitis, which would be partially derived from the combination of GL and GS, in TNBS-colitis model.

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