[Show abstract][Hide abstract] ABSTRACT: Resveratrol has been shown to mimic the beneficial effects of dietary restriction (DR). We previously reported that DR delays stroke onset and extends the lifespan in Stroke-Prone Spontaneously Hypertensive rats (SHRSP). Therefore, we examined whether resveratrol mimics DR and delays stroke onset in SHRSP.
Cerebrovascular endothelial cells (CVECs) from SHRSP were treated with resveratrol, and the inflammatory gene expression levels and NFκB protein levels were measured. In order to address the effects of resveratrol in vivo, SHRSP (male, 10 weeks of age) were fed an experimental diet containing several doses of resveratrol (0 - 0.05% (w/w)), after which we measured the plasma cytokine levels and examined the stroke onset and lifespan.
Treatment with resveratrol (100 μM, 24 hours) in CVECs from SHRSP significantly decreased the interleukin (IL)-1β-induced monocyte chemoattractant protein-1 (MCP-1) mRNA expression levels and p50 and p65 protein levels in the nuclear fraction. When the SHRSP were fed a diet containing resveratrol for one week, the resveratrol treatment did not affect the plasma lipid and glucose levels, body weight or weight of each tissue. Resveratrol slightly, but not significantly, decreased the plasma levels of IL-1β and MCP-1 compared with that observed in the control group. In addition, resveratrol decreased the IL-1β and MCP-1 mRNA expression levels in the brain versus the control animals. However, no doses of resveratrol delayed stroke onset or extended the lifespan in SHRSP.
In this study, resveratrol did not delay stroke onset in SHRSP, although it partially suppressed systemic and cerebral inflammation. These results suggest that resveratrol does not mimic the beneficial effects of DR on stroke in vivo.
Full-text · Article · Apr 2015 · Journal of atherosclerosis and thrombosis
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] ABSTRACT: Recently, people have used dietary supplements not only for nutritional supplementation, but also for treatment of their diseases. However, use of dietary supplements to treat diseases, especially with medications, may cause health problems in patients. In this study, we investigated use of dietary supplements in patients in Japan. This survey was conducted from January to December 2012, and was completed by 2732 people, including 599 admitted patients, 1154 ambulatory patients, and 979 healthy subjects who attended a seminar about dietary supplements. At the time of the questionnaire, 20.4% of admitted patients, 39.1% of ambulatory patients, and 30.7% of healthy subjects were using dietary supplements, which including vitamin/mineral supplements, herbal extracts, its ingredients, or food for specified health uses. The primary purpose for use in all groups was health maintenance, whereas 3.7% of healthy subjects, 10.0% of ambulatory patients, and 13.2% of admitted patients used dietary supplements to treat diseases. In addition, 17.7% of admitted patients and 36.8% of ambulatory patients were using dietary supplements concomitantly with their medications. However, among both admitted patients and ambulatory patients, almost 70% did not mention dietary supplement use to their physicians. Overall, 3.3% of all subjects realized adverse effects associated with dietary supplements. Communication between patients and physicians is important to avoid health problems associated with the use of dietary supplements.
[Show abstract][Hide abstract] ABSTRACT: As an adverse event, it has been reported that anticoagulation activity of warfarin was enhanced by simultaneous intakes of glucosamine and chondroitin sulfate. However, it is unclear whether these is a causative relation. Therefore, in the present study, we evaluated whether glucosamine and chondroitin sulfate enhanced the anticoagulant action of warfarin in mice in vivo, focusing on hepatic cytochrome P450 (CYPs)-mediated mechanisms. Mice were fed a diet containing various doses of glucosamine or chondroitin sulfate (0, 0.3, 1% (w/w)) for 2 weeks, and given warfarin by gavage on the last 2 days of the treatment regimen. Doses of glucosamine and chondroitin sulfate were 443 mg/kg and 464 mg/kg in the 0.3% diet groups, and 1523 mg/kg and 1546 mg/kg in the 1% diet groups. We found that 1% glucosamine significantly shortened prothrombin time and thrombotest Owen in animals given warfarin. However, the two ingredients did not induce or inhibit hepatic CYPs, including (S)-warfarin hydroxylase. These findings suggest that glucosamine and chondroitin sulfate do not affect the anticoagulation activity of warfarin through hepatic CYP mediated-mechanisms.
Full-text · Article · Aug 2014 · Journal of the Food Hygienic Society of Japan (Shokuhin Eiseigaku Zasshi)
[Show abstract][Hide abstract] ABSTRACT: This in vivo study in rats evaluated whether Coleus forskohlii extract (CFE) taken orally interacted with tolbutamide, a hypoglycemic drug metabolized by CYP2C enzymes. Rats were fed 0%, 0.3%, 1% (w/w) CFE diet for 2 weeks, followed by 0% CFE diet for 1 day. They were then given 40 mg/kg tolbutamide by intragastric gavage. Blood glucose level was determined up to 6 h after tolbutamide administration. CFE treatment increased total CYP content and various CYP subtypes in the liver. In particular, increases in activity and protein expression were noted for the CYP2B, CYP2C, and CYP3A subtypes. CFE treatment dose-dependently attenuated both the hypoglycemic action of tolbutamide at 6 h and the plasma concentration of tolbutamide. The activity of (S)-warfarin 7-hydroxylase, a CYP2C enzyme was negatively correlated with plasma tolbutamide level, which also showed a negative correlation with the reduction of blood glucose level. These results indicate that CFE induced hepatic CYPs in rats and attenuated the hypoglycemic action of tolbutamide via a hepatic CYP2C-mediated mechanism.
Full-text · Article · Jul 2014 · Journal of the Food Hygienic Society of Japan (Shokuhin Eiseigaku Zasshi)
[Show abstract][Hide abstract] ABSTRACT: Food for Specified Health Uses (FOSHU) can have beneficial effects on health when consumers correct their lifestyle appropriately. However, it is not clear whether consumers recognize the characteristics of FOSHU and use it appropriately. To address this issue, a questionnaire investigation was conducted. This revealed that most consumers took FOSHU to maintain their health, although a proportion of them did so for prevention or treatment of disease. FOSHU is appropriately labeled to indicate the correct daily intakes and mode of intake. About 60% of users followed these directions, but 20% did not, and the remainder were unaware of these recommendations. In this situation, only 23.4% of users gained beneficial effects from FOSHU. Secondary analysis showed that 30.2% of users who changed their dietary habit, 17.0% who changed their exercise habit, and 10.1% who did not change anything received beneficial effects from FOSHU. In addition, some users on medication used FOSHU that had similar health claims to medicines. This investigation confirmed the inappropriate usage of FOSHU, especially by patients and individuals on medication. These results suggest that consumers do not understand the characteristics of FOSHU, and should be educated about the appropriate use of FOSHU.
Full-text · Article · Jan 2014 · Nihon Eiyō Shokuryō Gakkai shi = Nippon Eiyō Shokuryō Gakkaishi = Journal of Japanese Society of Nutrition and Food Science
[Show abstract][Hide abstract] ABSTRACT: From studies in mice, we have reported that Coleus forskohlii extract (CFE), a popular herbal weight-loss ingredient, markedly induced hepatic drug metabolizing enzymes, especially cytochrome P450 (CYP), and interacted with co-administered drugs. This study was designed to examine how the induction of drug metabolizing enzymes by CFE was influenced by different levels of macronutrients in the diet. Mice were fed a non-purified diet or semi-purified diet with and without CFE (0.3-0.5%) for 14-18 d, and changes in the ratio of liver weight to body weight, an indicator of hepatic CYP induction, and hepatic drug metabolizing enzymes were analyzed. The ratio of liver weight to body weight, content and activities of CYPs, and activity of glutathione S-transferase were higher in a semi-purified standard diet (AIN93G formula) group than in high sucrose (62.9%) and high fat (29.9%) diet groups. Different levels of protein (7%, 20%, and 33%) in the diets did not influence CFE-induced CYP induction or increase the ratio of liver weight to body weight. The effect of CFE on the ratio of liver weight to body weight was higher with a semi-purified diet than with a non-purified diet, and was similar between dietary administration and intragastric gavage when the CFE dose and the diet were the same. There was a positive correlation between CFE-induced CYP induction and the content of starch in the diets, suggesting that dietary starch potentiates CFE-induced CYP induction in mice. The mechanism of enhanced CYP induction remains unclear.
Full-text · Article · Mar 2013 · Journal of Nutritional Science and Vitaminology
[Show abstract][Hide abstract] ABSTRACT: Herb-drug interactions are mainly mediated by hepatic cytochrome P450 (CYP) enzymes. Here, we examined the effect of three herbs (valerian, salacia and black cohosh) on CYP activity in vivo in mice and in liver microsomes in vitro. Extracts which showed activity in the preliminary tests were then fed to mice at various doses (0, 0.5, 1.5 and 4.5%). Valerian did not show any effect on hepatic CYPs. Black cohosh increased the liver weight, total CYP content and CYP activities (2B and 3A) in a dose-dependent manner (up to 4.5%). Salacia inhibited CYP1A2 activity in liver microsomes in vitro. Also, salacia at the dietary dose of 4.5% suppressed body weight gain, decreased hepatic total CYP content and increased CYP activities (1A1, 2B and 2C). These findings suggest that black cohosh and salacia at high dose affect the activity of hepatic CYPs, and therefore may interact with drugs that are metabolized by CYP.
Full-text · Article · Feb 2013 · Journal of the Food Hygienic Society of Japan (Shokuhin Eiseigaku Zasshi)
[Show abstract][Hide abstract] ABSTRACT: We investigated the characteristics of dietary supplements and their use by 1,076 Japanese pregnant women, the majority of whom were in mid- to late pregnancy. The subjects completed a self-reported survey on their sociodemographic characteristics, supplement use, and attitudes towards diet. The overall prevalence of supplement use did not change before and after pregnancy (75%); however, daily use increased by approximately twofold with pregnancy (20.2% versus 37.2%). After the onset of pregnancy, supplements containing folic acid were taken for fetal health. Daily users were more likely to be older, have a greater awareness of the risk of neural tube defects (NTD), view supplement use as acceptable, have less diet anxiety, and have more advisers regarding diet. Respondents used supplements containing folic acid alone or with other ingredients. Folic acid intake is recommended to reduce the risk of NTD. However, supplement use began after pregnancy recognition, suggesting a lack of knowledge on the appropriate timing of folic acid use. Information about supplements was obtained mostly from newspapers, magazines, flyers, and stores. These results indicate that more accurate information regarding the optimal timing of folic acid intake and the safety of dietary supplements must be disseminated.
No preview · Article · Jan 2013 · Asia Pacific Journal of Clinical Nutrition
[Show abstract][Hide abstract] ABSTRACT: Objective: Folic acid intake is recommended for fertile women to reduce the risk of neural tube defects in infants. However, the rationale behind this recommendation may not be properly understood. A preliminary study was conducted to examine the current understanding of folic acid and dietary supplementation and associated problems among pregnant women, dietitians, and students attending dietetics or nursing training schools.Methods: The subjects of this survey were pregnant women who attended pre-natal classes in a local government or maternity hospital (Tokyo and Hokkaido), participants of lectures about dietary supplements for dietitians (Tokyo, Kanagawa, and Hiroshima), and students attending dietetics or nursing training schools (Nagano and Hiroshima) from October to December 2011. The survey was conducted with an anonymous, self-reported questionnaire.Results: Responses were obtained from 104 pregnant women, 69 dietitians, and 175 students. The effective recovery rates were 54.5%, 51.1%, and 65.8%, respectively. Although more than 90% of the subjects were familiar with the term folic acid, they had inadequate knowledge on the appropriate timing and recommended folic acid intake.Conclusions: This study was preliminary in nature in that it entailed a small number of participants. However, the data suggest the need to provide detailed information about the association between folic acid intake and neural tube defect risk reduction, such as the appropriate intake timing and amount and the actual situation regarding dietary supplements, for pregnant women, dietitians, and students attending dietetics or nursing training schools.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
This study aimed to determine whether Coleus forskohlii extract (CFE) influences the anticoagulant action of warfarin in mice in vivo and its relationship with hepatic cytochrome P450 (CYP).
Mice were fed various doses of CFE standardised with 10% forskolin in a normal diet for one week, or in protein diets containing 7% and 20% casein (low and normal) for four weeks. They were then administered with warfarin by gavage on the last two days of the treatment regimen, and blood coagulation parameters, as well as hepatic CYP, were analysed at 18 h after the last dose. Direct interaction between CFE and forskolin with CYP2C was evaluated in vitro.
CFE dose dependently increased hepatic total CYP content and S-warfarin 7-hydroxylase activity at a dietary level of ≥0.05%. Warfarin-induced anticoagulation was attenuated by CFE in parallel with CYP induction. The findings were similar in mice fed diets containing CFE and different ratios of protein. CFE directly inhibited CYP2C activity in mouse and human liver microsomes in vitro, whereas forskolin was only slightly inhibitory.
CFE attenuates the anticoagulant action of warfarin by inducing hepatic CYP2C; thus, caution is required with the combination of warfarin and dietary supplements containing CFE.
[Show abstract][Hide abstract] ABSTRACT: Drug-herb interaction is a major concern for the safety use of herbal products. In our previous mice study, we found that Coleus forskohlii extract (CFE) markedly induced hepatic cytochrome P450 (CYP), especially CYP2B, 2C and 3 A type at the dose added to weight loss supplements. Also, we showed that forskolin, an active constituent in CFE, was not involved in the CYP induction in vivo. The present study was designed to estimate the compounds inducing CYP. CFE was fractionated into 4 (diethyl ether-, ethyl acetate-, acetone-, the remainder), and the effect of those fractions on CYP was examined in two systems: test materials were fed to mice for 2 weeks (in vivo system), and those were directly added to CYP3A enzyme assay (in vitro system). It was found that CYP inducing activity in vivo was mainly distributed in the diethyl ether-fraction, which also showed a direct inhibition of CYP3A activity in vitro. The water soluble fraction showed neither CYP induction in vivo nor CYP3A inhibition in vitro. It was also suggested the existence of several compounds inducing CYP, some of which was eliminated during the fractionation procedure. CFE-induced CYP induction in vivo was well correlated with an increase in liver weight, and was related to direct inhibition of CYP enzyme activity in vitro. Combination of these characteristics would be useful for further study to identify the active constituents in CFE materials that induce CYP.
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] ABSTRACT: Ginkgo biloba extract (GBE) is a popular herbal ingredient used worldwide, but it is reported to induce bleeding as a serious adverse event. In this study we examined whether GBE induced spontaneous bleeding or accelerated warfarin anticoagulation via herb-drug interaction. Mice were given GBE or various active components of GBE orally for 5 days and blood coagulation parameters and hepatic cytochrome P450 enzymes (CYPs) were measured. Mice also received warfarin (racemate, (S)- or (R)-enantiomer) for the last 3 days of the 5-day regimen to examine GBE-warfarin interactions. Neither GBE (up to 1000 mg/kg) nor ginkgolide B (up to 140 mg/kg), a platelet-activating factor antagonist, influenced blood coagulation parameters. In contrast, GBE attenuated the anticoagulant action of warfarin. Bilobalide, a component of GBE that markedly induced hepatic CYPs including (S)-warfarin hydroxylase, showed similar effects. For (S)-warfarin, the anticoagulation action and the interaction with GBE was clear, while the influence on metabolism was greater for (R)-warfarin than for (S)-warfarin, which corresponded to the CYP types induced by GBE. These results suggest that GBE and ginkgolide B have no influence on blood coagulation in vivo, and that GBE attenuates the anticoagulation action of warfarin via induction of hepatic CYPs by bilobalide.
No preview · Article · Jul 2011 · Phytomedicine: international journal of phytotherapy and phytopharmacology
[Show abstract][Hide abstract] ABSTRACT: We compared ascorbic acid (AA) levels in the blood and TPA- and fMLP-stimulated superoxide (O(2)(•-)) production in neutrophils of pre-, early, and late hypertensive stroke-prone spontaneously hypertensive rats (SHRSP) with those of age-matched Wistar Kyoto rats (WKY), or two other normotensive strains of rats. Plasma and lymphocyte AA levels were about two-fold higher in SHRSP as early as 4 weeks old compared to WKY, and also higher than those of Wistar and Sprague-Dawley (SD) rats. Levels of AA were high in the liver and adrenal glands of SHRSP, indicating congenitally high AA levels. The production of O(2)(•-) in neutrophils was about two-fold higher in SHRSP than in WKY even at 4 weeks of age, and increased with age in both strains. Among SHRSP, AA levels in lymphocytes decreased at the late hypertensive stages with a decrease in hepatic l-gulono-γ-lactone oxidase (GLO) activities. These data suggest that bi-phasic AA levels in the blood of SHRSP comprise congenitally high levels and a decrease after persistent hypertension due to enhanced O(2)(•-) production and a decrease in de novo AA synthesis through GLO.
No preview · Article · Jun 2011 · Clinical and Experimental Hypertension