In this article, I reviewed our prior clinical and experimental studies about the effects of chotosan, a Kampo formula, on cerebrovascular disorders. A double-blind randomized controlled trial demonstrated that chotosan was effective on accompanying symptoms of vascular dementia. Chotosan improved microcirculation and hemorheological factors in patients with asymptomatic cerebral infarction. This formula inhibited the elevation of blood pressure, protected endothelial function, and prolonged the life span of stroke-prone spontaneously hypertensive rats. The phenolic fraction of Uncaria sinensis (US), a main medicinal plant of chotosan, had endothelium-dependent relaxation effect, and its alkaloid fraction possessed endothelium-independent relaxation effect. It was revealed that US had neuroprotective effects on glutamate- and NO donor-induced neuronal death in cultured neurons. Chotosan and US had protective effects on delayed neuronal death after transient forebrain ischemia in gerbils, and enhanced superoxide anion and hydroxyl radical scavenging activities as well as catalase activity in the brain. All of these results suggest that chotosan has such multiple pharmacological actions as improving effect on microcirculation, protective effect on endothelial function and neuroprotective effect. Therefore chotosan might be useful for prevention of the development of cerebrovascular disorders.

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The effect of 70% methanolic extract of Red Ginseng (Panax ginseng C. A. MEYER, RG-ext) was investigated on blood fluidity in rats. Evaluation of blood fluidity was carried out by measuring whole blood passage time using a micro channel array flow analyzer (MC-FAN), polybrene-induced erythrocyte aggregation (PEA), and the euglobulin lysis time (ELT). RG-ext inhibited the elongation of the passage time caused by cold stress (5°C), whereas White Ginseng extract (WG-ext) showed no effect. In addition, RG-ext showed inhibition of PEA. The aggregation inhibitory activity of RG-ext was stronger than that of WG-ext. These data indicated that effects of RG-ext on blood fluidity are superior to those of WG-ext. Successive oral administration of RG-ext (50 and 200 mg/kg, p.o.) to adjuvant-induced arthritis model rats inhibited the elongations of both the whole blood passage time and ELT caused by arthritis, although RG-ext showed no effect on right hind paw swelling. In order to identify active constituents, the effects of several Ginseng saponins [ginsenoside-Ro, -Rb₁, -Rg₁ and 20(S)-ginsenoside-Rg₃ [20(S)-Rg₃]] in Red Ginseng on the elongation of whole blood passage time in low temperature-treated rat blood and PEA were examined. Among these, 20(S)-Rg₃, a saponin characteristic of Red Ginseng, showed the most potent inhibitory activity on elongation of whole blood passage time and showed concentration-dependent inhibition of PEA. Therefore, part of the effect of Red Ginseng on improving blood fluidity may be attributable to 20(S)-Rg₃.

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Certain ingredients in Kampo medicines are known to be converted into the active form by bacterial flora in the intestine. Conversely, enteric microbiota is supposed to be affected by Kampo medicines, because the medicines comprise numerous compounds with prebiotic and/or antimicrobial properties. However, the effect of Kampo medicines on the bacterial flora has rarely been studied. In this study, the effects of different types of Kampo medicines on bacterial flora were investigated. Male IQI mice were orally treated with juzentaihoto, hochuekkito, kakkonto, and orengedokuto extract solutions (1 g/kg body weight) or water daily for 14 days. To examine the changes in the intestinal microflora, the terminal restriction fragment polymorphism (T-RFLP) method was used. Cluster analyses suggested that T-RFLP profiles of juzentaihoto/hochuekkito ("hozai") and orengedokuto/kakkonto ("Shazai") are classified into 2 different clusters in the dendrogram. To examine changes in 5 genera of common bacteria (Bifidobacterium, Lactobacillus, Clostridium, Escherichia coli, and Bacteroides fragilis), real-time PCR was performed. No large-scale changes were observed except for modest but significant decrease in Lactobacillus numbers by juzentaihoto as well as several hundred-fold increase in Escherichia coli numbers by hochuekkito. The present study indicates that DNA-based methods for the analysis of microbiota may pave the way for elucidation of the complicated and pleiotropic influences of the components of Kampo medicines on enteric flora.

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Effects of Henseki were examined on HC･HF (High Carbohydrate and High Fat) diet-induced obesity in mice. Henseki prevented an increase in the body weight and visceral fat accumulation induced by the HC･HF diet. The results were almost comparable to those reported in the clinical studies. Henseki showed preventive effects on the body weight gain in a dose-depending manner in the latter administration period. Therefore, consecutive administrations of Henseki would be considered to induce the anti-obesity effect. Henseki prevented decreases of the diet-induced thermogenesis and basal metabolism. It was concluded that Henseki was considered to stimulate energy expenditure in the body.

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A simple, efficient and reliable HPLC-DAD method for the simultaneous quantification of ephedrine, pseudoephedrine, paeoniflorin, puerarin, glycyrrhizic acid, cinnamic acid, cinnamaldehyde and 6-gingerol in kakkonto decoction, a traditional herbal medicine, containing 7 crude drugs was developed and validated for the first time. The method was validated by determining the linearity, range, limit of detection, limit of quantification, precision, accuracy and specificity, and was successfully applied to the analysis of the 8 components in kakkonto decoction and the 5 components in maoto decoction which contains some of same crude drugs with kakkonto. This method can be applied to the routine study and quantification of the major characteristic components in kakkonto decoction. It may also be used for other traditional herbal medicine formulas which contain the same crude drugs or characteristic components studied in this paper.

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