Yuko Yamazaki

Jumonji University, Saitama, Saitama, Japan

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Publications (8)16.76 Total impact

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    ABSTRACT: Coleus forskohlii extract (CFE), an herbal ingredient, is used for weight-loss products. CFE's alleged efficacy is attributed to forskolin. However, CFE has been shown to induce fatty liver in mice, with components other than forskolin playing a part in this effect. The present study addressed the underlying mechanism of CFE-induced fatty liver by analyzing changes in CFE-treated mice of lipid concentrations and of the levels of mRNAs encoding enzymes and transcription factors known to be related to fatty liver. Mice were fed a diet containing 0, 0.3 and 1% CFE for 2 weeks. CFE at 1% clearly induced fatty liver, as demonstrated by histological examination and confirmed by increases in triglyceride concentrations in liver. However, treated mice did not exhibit elevation in plasma levels of non-esterified fatty acids. Comprehensive analysis of liver mRNA levels revealed accumulation of multiple transcripts, including mRNAs encoding enzymes acetyl-CoA carboxylase and long-chain elongase; transcription factor peroxisome proliferator-activated receptor gamma (PPARγ); and lipid-droplet-associated fat-specific protein 27 (Fsp27). These findings suggest that the de novo synthesis and accumulation of triglyceride in the liver, through the enhanced expression of specific lipogenic mRNAs, is a major underlying mechanism of fatty liver induction by CFE.
    Full-text · Article · Dec 2014 · Toxicology Reports
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    ABSTRACT: In an attempt to develop d-sorbose as a new sweetener that could help in preventing lifestyle-related diseases, we investigated the inhibitory effect of d-sorbose on disaccharidase activity, using the brush border membrane vesicles of rat small intestines. The inhibitory effect was compared with that of l-sorbose and other rare sugars, and the small intestinal disaccharidases in rats was compared with that of humans as well. In humans and the small intestines of rats, d-sorbose strongly inhibited sucrase activity and weakly inhibited maltase activity. Inhibition by d-sorbose of sucrase activity was similar to that of l-arabinose, and the Ki of d-sorbose was 7.5 mM. Inhibition by d-sorbose was very strong in comparison with that of l-sorbose (Ki, 60.8 mM), whereas inhibition of d-tagatose was between that of d-sorbose and l-sorbose. The inhibitory mode of d-sorbose for sucrose and maltase was uncompetitive, and that of l-sorbose was competitive. To determine a suppressive effect on postprandial blood levels of glucose and insulin via inhibition of sucrase activity, sucrose solution with or without d-sorbose was administered to rats. Increments in the blood levels of glucose and insulin were suppressed significantly after administration of sucrose solution with d-sorbose to rats, in comparison to administration of sucrose solution without d-sorbose. In contrast, the suppressive effect of l-sorbose on postprandial blood levels of glucose and insulin was very weak. These results suggest that d-sorbose may have an inhibitory effect on disaccharidase activity and could be used as a sweetener to suppress the postprandial elevation of blood levels of glucose and insulin. The use of d-sorbose as a sweetener may contribute to the prevention of lifestyle-related diseases, such as type 2 diabetes mellitus.
    No preview · Article · Sep 2014 · Nutrition Research
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    ABSTRACT: Coleus forskohlii root extract (CFE) is popular for use as a weight loss dietary supplement. In this study, the influence of standardized CFE containing 10% active component forskolin on the hepatic drug metabolizing system was investigated to evaluate the safety through its drug interaction potential. Male ICR mice were fed AIN93G-based diets containing 0-5% CFE or 0.05% pure forskolin for 2-3 weeks. Intake of two different sources of 0.5% CFE significantly increased the relative liver weight, total content of hepatic cytochrome P450 (CYP) and induced CYPs (especially 2B, 2C, 3A types) and glutathione S-transferase (GST) activities. CFE significantly increased mRNA expression of CYPs and GST with dose related responses. However, unlike the CFE, intake of 0.05% pure forskolin was found to be associated with only weak induction in CYP3A and GST activities with no significant increases in relative liver weight, total hepatic content or other CYPs activities. The inductions of CYPs and GST by CFE were observed at 1 week of feeding and rapidly recovered by discontinuation of CFE. These results indicated the induction potential of CFE on CYPs, and that this effect was predominantly due to other, as yet unidentified constituents, and not forskolin contained in CFE.
    Full-text · Article · Dec 2011 · Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association
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    ABSTRACT: Zinc (Zn) is an essential trace element for DNA synthesis and for cell growth and differentiation. The deficiency induces a wide range of disorders including immunodeficiency. In this study, the influence of Zn deficiency to the mice infected with Babesia microti was examined, and was compared with the influence in the rats infected with B. rodhaini previously reported. Experiments of B. microti infection were conducted using Zn-deficient (ZD; allowed to eat ad libitum on the ZD diet), Zn-adequate (ZA; allowed to eat ad libitum on the ZA diet), and diet-restricted (DR; supplied 2 g/day on the ZA diet) mice. It was suggested that the Zn deficiency exacerbated the infection dynamics of the mice with B. microti by the growth retardation, the reduction of immunity and the decrease in PCV. The results in the mice supported the consequences in the rats previously reported.
    No preview · Article · Feb 2011 · Journal of Veterinary Medical Science
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    ABSTRACT: 健常成人女性へD-タガトース (TAG) を摂取させ, 一過性下痢に対する最大無作用量を測定した。次に, TAG 摂取による血糖値およびインスリン濃度への影響, TAG の血中濃度および尿中排泄量ならびにTAG 摂取後の呼気水素ガス排出量を測定し, TAG の小腸からの消化・吸収性ならびに大腸における発酵性, 腸内細菌による資化性などを観察し, D-タガトースの生体における運命を検討した。TAG の最大無作用量は0.25 g/kg体重で, D-ソルビトールと同程度であった。TAG 5 gおよび10 gを摂取させた場合, TAG 血中濃度は検出限界以下であった。また, 摂取後6時間までの尿中排泄量は摂取量の2%以下であった。血糖値および血清インスリン濃度はTAG 摂取によって変化せず, 呼気水素ガス排出はTAG 5 g摂取では観察されず, 10 g摂取で明らかに増加した。しかし, フラクトオリゴ糖の同量摂取に比べると量的に少なく, 排出開始時間は遅延した。また, ヒト糞便培養実験におけるTAGからの有機酸生成量は少なく, 大腸へ到達したTAG が腸内細菌によってわずかに短鎖脂肪酸へ代謝されることが示唆された。以上の結果, TAG 10 g摂取では下痢は誘発されず, 5 g程度が小腸から吸収され, 摂取量の2%程度が代謝されずに尿中へ排泄されると推定された。これらの結果に基づいてTAGの有効エネルギー量を推算したところ, TAGのエネルギー換算係数は2 kcal/gに分類された。
    No preview · Article · Jan 2011
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    ABSTRACT: A single dose by gavage of bilobalide (30 mg/kg) was found to produce a time-dependent induction of hepatic cytochrome P450 (CYP) enzyme activity and protein expression in rats. An RT-PCR study further showed that mRNA expression of CYP2B was maximal at 6 h. Plasma and liver bilobalide concentration in rats following administration of Ginkgo biloba extract equivalent to bilobalide of approximately 40 mg/kg showed a similar response to that exhibited by mRNA expression. These findings suggest that bilobalide markedly induced hepatic CYPs, but the induction could be mitigated due to rapid elimination from the liver.
    No preview · Article · Apr 2009 · Journal of Pharmacological Sciences
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    ABSTRACT: Commercial products containing the kava plant (Piper methysticum), known to have the anxiolytic activity, are banned in several European countries and Canada because of the suspicion of a potential liver toxicity. In some reports, kava and kavalactones (major constituents of kava) inhibited activities of cytochrome P450 (CYP) isoforms including CYP1A2. On the other hand, a few studies showed that administration of kava to rats moderately increased CYP1A2 proteins in the liver. CYP1A isoforms are likely responsible for the metabolic activation of potent carcinogenic environmental toxins such as aflatoxins, benzo[a]pyrene, and others. On these bases, we have investigated the effects of administration of commercial kava products on gene expression of hepatic CYP1A isoforms in rats. A high dose (equivalent to approximately 380 mg kavalactones/kg/day; 100 times of the suggested dosage for human use) of two different types of kava products for 8 days significantly increased liver weights. CYP1A2 mRNA expression was moderately increased (2.8–7.3 fold). More importantly, the high dose of kava markedly enhanced CYP1A1 mRNA expression (75–220 fold) as well as ethoxyresorufin O-deethylase activities and CYP1A1 immunoreactivities. Thus, no observed adverse effect levels of kavalactones would be lower than 380 mg/kg/day. When the safety factor of kavalactones is assumed to be 100, a value most often used upon the risk analysis of chemicals and designed to account for interspecies and intraspecies variations, a number of kava product users likely ingest more kavalactones than acceptable daily intakes. Based on overall evidence, we should pay considerable attention to the possibility that kava products induce hepatic CYP1A1 expression in human especially in sensitive individuals.
    No preview · Article · Dec 2008 · Food and Chemical Toxicology
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    ABSTRACT: Currently, adverse reactions to herbal remedies as the result of herb-drug interactions have received a great deal of attention. GBE, one of popular herbal medicine, is used by elderly people for treatment such as dementia. People who take GBE tend to be elderly, and GBE-drug interactions are a matter of concern. Our previous studies showed existence of GBE-drug interaction via induction of hepatic CYPs [1,2]. As GBE is a natural product, exact components of GBE may vary among products. For clear understanding of GBE-drug interactions and better use of GBE, it is necessary to identify and characterize the mode of action of substance responsible for inducing CYPs. In this study, fractionated GBE samples were prepared and orally given to mice to identify the substance inducing CYPs. It was found that terpenoid fraction, particularly bilobalide rich fraction, showed highest CYP inducing activity. When several terpenoids of GBE (ginkgolide A, B, C and bilobalide) were orally given to mice for 5 days, marked induction of CYPs was detected by bilobalide, but not by other terpenoids. Details of enzyme induction by bilobalide were examined in rats by analyzing hepatic CYPs activity and mRNA expression. Oral administration of bilobalide increased CYPs activity at 6-24 hr post treatment, and increased mRNA expression at 6 hr. When bilobalide in blood was monitored in rats given excess GBE, the concentration increased about 1-2 hr and decreased to the undetectable level at 24 hr. These findings suggest that bilobalide in GBE cause a remarkable induction of CYPs and may cause interaction with drugs, but the interaction could be easily eliminated by stopping the intake. It will be necessary to standardize bilobalide content in GBE products to avoid GBE-drug interaction. 1. Sugiyama T et al., Life Sci; 75: 1113-22(2004). 2. Uchida S et al., J Clin Pharmacol; 46: 1290-8(2006).
    No preview · Conference Paper · Jan 2008