It has been almost ten years since Huaier products were first introduced to Japan as a health food. Due to its positive results on tumor treatment, Huaier became a notable Traditional Chinese Medicine and even, doctors of Kampo Medicine, Complementary and Alternative Medicine, and Integrative Medicine in Japan are gradually becoming aware of it. In fact, Huaier products have also been confirmed to be effective against noncancer-related diseases, such as respiratory and kidney diseases. In this paper, we summarized and discussed in detail scientific evidences supporting its application to diseases other than cancer.

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Objective: Acanthopanax senticosus Harms extract (ASE) is an ingredient of functional foods, such as health supplements, in Japan. We investigated the effects of ASE on CYP2C9 activity.
Methods and Results: CYP2C9-catalyzed diclofenac 4′-hydroxylase activities in human intestinal and liver microsomes (abbreviated as HIM and HLM, respectively) were significantly decreased by the addition of ASE in a concentration-dependent manner. Kinetic studies of diclofenac 4′-hydroxylase in HLM revealed that ASE addition significantly decreased V_max but had no effect on K_m. These results suggest that diclofenac 4′-hydroxylase activity is suppressed by ASE addition in a non-competitive manner. Then, we investigated the time courses of diclofenac 4′-hydroxylase activity in rat liver microsomes after ASE oral administration (50 to 400 mg/kg). Diclofenac 4′-hydroxylase activities were significantly lowered by the administration of 200 and 400 mg/kg ASE at 0.5 to 4 hr compared with control (0 hr). Furthermore, we investigated the effects of ASE oral administration on the pharmacokinetics of tolbutamide (substrate for CYP2C9) in rats. The area under the concentration-time curve of tolbutamide after ASE oral administration (400 mg/kg) was enhanced by approximately 1.6 times compared with that without ASE oral administration.
Conclusion: These findings indicated that ASE inhibits human intestinal and hepatic CYP2C9 activities.

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Objective: By using human liver microsomes (HLM), we analyzed the effects of 14 known components of A.senticosus Harms on the activities of CYP2C9 and CYP3A4.
Methods and Results: Sesamin and quercetin inhibited both enzyme activities, whereas quercitrin strongly inhibited CYP3A4 activity. The 50% inhibitory concentrations (IC₅₀s) of sesamin and quercetin on CYP2C9 activity were approximately 124- and 59-fold higher and the IC₅₀s of sesamin, quercetin, and quercitrin on CYP3A4 activity were approximately 427-, 135-, and 22-fold higher than that of A. senticosus Harms extract (ASE), respectively. All these components inhibited both CYP3A4 and CYP2C9 in a non-competitive manner. However, these components are present in small amounts in ASE.
Conclusion: Therefore, the food-drug interactions caused by A. senticosus Harms are presumed to be due to the additive or synergistic interaction of these components or the other existing components, including their metabolites.

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The inhibitory effects of the freeze-dried powder of the aqueous extract of black tea leaf (JAT) on α-glucosidase activity were investigated. We initially examined the effects of JAT addition on yeast α-glucosidase activity. JAT significantly and dose-dependently inhibited α-glucosidase activity and more strongly inhibited the activity than acarbose, the positive control. Then, we examined the effects of oral administration of JAT on sucrose tolerance in type 2 diabetes mellitus model db/db mice. Both JAT and acarbose administered groups showed a dose-dependent decrease in plasma glucose levels after the sucrose loading compared with the control group. Notable was that the plasma glucose levels of the 500 mg/kg JAT administered group exhibited a significant decrease 30 min or longer after the sucrose loading. On the other hand, no significant difference in plasma insulin levels was seen between the JAT administered group and the control group. We also measured small intestinal sucrase activity in db/db mouse at 30 min after JAT oral administration. Compared to control mice, small intestinal sucrase activity was significantly decreased in the 500 mg/kg JAT administered mice. These findings indicate that JAT may be a useful natural material for the prevention and therapy of type 2 diabetes mellitus.

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Folic acid contained in potato (Solanum tuberosum L.) tubers is concentrated in potato chips by dehydration during frying. It is a vitamin recommended to young women which helps protect fetus from congenital disease. Additionally, folic acid can lower plasma homocysteine concentrations, a known independent risk factor for cardiovascular disease. This study was designed to determine whether the dietary consumption of potato chips affect serum folic acid concentration and plasma homocysteine concentration in human subjects. Results showed a significant increase in serum concentrations of folate 1, 3, and 6 hours after ingestion. Vitamin B₆, on the other hand, increased significantly after 3 hours of intake. In contrast, plasma homocysteine concentration decreased significantly 6 hours after ingestion. These results suggest that potato chips would be a good dietary source of folic acid for humans.

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Objectives: To examine in two tests the potential of kaki (persimmon) extract-containing diet (KE diet) to reduce malodorous volatile sulfur compounds (VSC), such as hydrogen sulfide (H₂S), methyl mercaptan (CH₃SH) and dimethyl sulfide (CH₃SCH₃), as well as on subjective fecal odor on healthy adults.
Methods: In the first test, 11 subjects were given garlic-containing soup. For a period of time, they were given a single dose of KE diet (150 mg as kaki extract) with water, and only water for the rest of the study period. Two hours after the administration, oral gas samples were collected from individual subjects and analyzed for VSC. In the second test, 14 subjects were given a single dose of KE diet for 7 days. Fecal samples were collected from individual subjects before and after the 7-day KE diet intervention. Levels of VSC were determined and the magnitude of subjective fecal odor was estimated based on ratings in the self-administered questionnaire.
Results: Levels of CH₃SCH₃ in oral gas were significantly lowered when subjects were on a KE diet. On the other hand, although decreases in the level of any VSC in feces before and after the 7-day KE diet intake did not reach a statistical significance, subjective fecal odor significantly improved by the KE diet intake.
Conclusion: KE diet appears to have a beneficial effect on VSC-associated oral malodor and subjective fecal odor.

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The present study was examined the effects of music therapy as complementary and alternative medicine (CAM) on the perspective of apathy in the behavioral and psychological symptoms of dementia (BPSD) for the elderly with dementia. Twenty elderly adults with dementia, whose a mean age was 85.9 year, were conducted the group music therapy using familiar songs which was carried out ten times for eight months biweekly. Significant improvements as a whole were observed in singing, rhythm activity and physical exertion in the area of “emotional response” and an improvement tendency was observed in power of concentration in the area of “sociality.” The elderly with Alzheimer-type dementia showed improvement tendencies in power of concentration, rhythm activity, singing and motivation to participation, while no improvement was found in those with cerebrovascular-type dementia. These results suggest that music therapy has an alleviation effect of the apathy perspective in BPSD and leads to improvement of QOL for the elderly with dementia, especially Alzheimer-type dementia. This means music therapy is useful for the elderly with dementia as CAM.

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Objective: Recently, we reported that long-term intake of a water-soluble extract from culture medium of Ganoderma lucidum mycelia (WER) reduced hyperglycemia and enhanced glucose transporter-4 (GLUT4) translocation to the plasma membrane in skeletal muscles and adipose tissue in KK-A^y mice, a type 2 diabetic animal model with obesity. In the present study, we investigated the effect of WER on hepatic carbohydrate metabolism.
Methods: Female KK-A^y mice were given free access to water and high-fat food containing 0.5% WER for 8 weeks, and blood glucose levels were assessed every week. At the end of the experimental period, the expression and activities of sugar metabolic enzymes in the liver were determined by Real Time RT-PCR and each activity measurement method. Also, the amount of glycogen was measured by anthrone-sulfuric acid method. Furthermore, the expression level of GLUT2 and activation of AMP kinase (AMPK) and glycogen synthase kinase 3β (GSk3β) was also determined by western blot analysis.
Results: The mice with the high-fat ingestion showed a gradual increase in the levels of blood glucose and body weight. In the WER-treated mice, the blood glucose level was suppressed after 2 weeks of intake. The gene expression and enzyme activities of both glucose-6-phosphatase and phosphoenolpyruvate carboxykinase were suppressed, whereas those of glucokinase were increased in the mice with WER intake and pioglitazone administration. The accumulation of glycogen was increased. Moreover the expression of GLUT2 and phosphorylation levels of AMPK and GSk3β were also increased in the mice with WER intake.
Conclusion: These results indicate that WER affects hepatic carbohydrate metabolism, which may derive from the suppression of gluconeogenesis through the modulation of related enzymes and enhancement of glucose uptake, glycolysis and glycogen synthesis.

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Objectives: Kurozu has long been used as a traditional fermented food product mainly in East Asia, including Japan; various health functions of Kurozu have been reported. This study examined its effects on body fat and energy metabolism by a double-blind placebo-controlled trial.
Methods: Mildly obese adults took a dietary supplement containing Kurozu concentrate for 12 weeks with approximately 10 min of exercise every day.
Results: A decline in hip circumference was observed in the group consuming the dietary supplement containing Kurozu. It was shown that fat-derived energy consumption increased while suppressing carbohydrate-derived energy consumption. Therefore, it was revealed that energy was derived from the fat consumed, and a tendency to increase the energy consumption at the time of exercise was also observed. Furthermore, negative correlations were observed between the initial fat volume and both the variation of the total fat area and the variation of the subcutaneous fat area in the examination group. It was revealed that larger the amount of body fat, greater the effect of Kurozu in decreasing the amount of fat. In addition, no safety issues were observed 12 weeks after ingesting the dietary supplement containing Kurozu concentrate, and it was confirmed as a safe food product.
Conclusion: Appropriate exercise and intake of the dietary supplement containing Kurozu concentrate contributed toward the improvement of the metabolic syndrome.

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