The Experts below are selected from a list of 2994 Experts worldwide ranked by ideXlab platform
Varanuj Chatsudthipong - One of the best experts on this subject based on the ideXlab platform.
-
Steviol slows renal cyst growth by reducing AQP2 expression and promoting AQP2 degradation.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2018Co-Authors: Rattikarn Noitem, Chatchai Muanprasat, Chaowalit Yuajit, Sunhapas Soodvilai, Varanuj ChatsudthipongAbstract:Abstract Overexpression of aquaporin 2 (AQP2) was observed and suggested to be involved in fluid secretion leading to cyst enlargement in polycystic kidney disease (PKD). The cyst expansion deteriorates the renal function and, therefore, therapies targeting cyst enlargement are of clinical interest. Of note, inhibition of vasopressin function using vasopressin 2 receptor (V2R) antagonist which decreased cAMP production along with AQP2 production and function can slow cyst growth in ADPKD. This finding supports the role of AQP2 in cyst enlargement. Steviol, a major metabolite of the sweetening compound stevioside, was reported to retard MDCK cyst growth and enlargement by inhibiting CFTR activity. Interestingly, its efficacy was found to be higher than that of CFTRinh-172. Since Steviol was also found to produce diuresis in rodent, it is likely that Steviol might have an additional effect in retarding cyst progression, such as inhibition of AQP2 expression and function. Here, we investigated the effect of Steviol on AQP2 function and on cyst growth using an in vitro cyst model (MDCK and Pkd1−/− cells). We found that Steviol could markedly inhibit cyst growth by reducing AQP2 expression in both Pkd1−/− and MDCK cells. Real-time PCR also revealed that Steviol decreased AQP2 mRNA expression level as well. Moreover, a proteasome inhibitor, MG-132, and the lysosomotropic agent, hydroxychloroquine (HCQ) were found to abolish the inhibitory effect of Steviol in Pkd1−/− cells. Increased lysosomal enzyme marker (LAMP2) expression following Steviol treatment clearly confirmed the involvement of lysosomes in Steviol action. In conclusion, our finding showed for the first time that Steviol slowed cyst growth, in part, by reducing AQP2 transcription, promoted proteasome, and lysosome-mediated AQP2 degradation. Due to its multiple actions, Steviol is a promising compound for further development in the treatment of PKD.
-
Steviol retards renal cyst growth through reduction of cftr expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease
Biochemical Pharmacology, 2014Co-Authors: Chaowalit Yuajit, Chatchai Muanprasat, Sureeporn Homvisasevongsa, Annarachel Gallagher, Sorin V Fedeles, Suticha Kittayaruksakul, Stefan Somlo, Varanuj ChatsudthipongAbstract:Cyst enlargement in autosomal dominant polycystic kidney disease (ADPKD) is associated with cAMP-activated proliferation of cyst-lining epithelial cells and transepithelial fluid secretion into the cyst lumen via cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel leading to renal failure for which no effective treatment is currently available. We previously reported that Steviol retards Madin-Darby canine kidney (MDCK) cyst enlargement by inhibiting CFTR channel activity and promoting proteasomal-mediated CFTR degradation. It is imperative to examine the effect of Steviol in animal models of ADPKD. Therefore, we examined the effect of Steviol on renal cyst growth in an orthologous mouse model of human ADPKD (Pkd1(flox/flox):Pkhd1-Cre). The results showed that daily treatment with both 200mg/kg BW of Steviol and 1000mg/kg BW of stevioside for 14 days markedly decreased kidney weight and cystic index in these mice. However, only Steviol markedly reduced blood urea nitrogen and creatinine values. Steviol also reduced cell proliferation but had no effect on cell apoptosis. In addition, Steviol suppressed CFTR and mTOR/S6K expression in renal cyst-lining epithelial cells. Interestingly, Steviol was found to stimulate AMP-activated protein kinase (AMPK). Our findings indicate that Steviol slows cyst progression in ADPKD mouse model, in part, through the activation of AMPK which subsequently inhibits CFTR chloride channel expression and inhibits renal epithelial cell proliferation via mTOR/S6K pathway. Most importantly, Steviol could markedly improve kidney function in a mouse model of ADPKD. Steviol thus has potential application for further development as a therapeutic compound for the treatment of polycystic kidney disease.
-
Steviol Reduces MDCK Cyst Formation and Growth by Inhibiting CFTR Channel Activity and Promoting Proteasome-Mediated CFTR Degradation
PloS one, 2013Co-Authors: Chaowalit Yuajit, Chatchai Muanprasat, Sureeporn Homvisasevongsa, Lisa Chatsudthipong, Sunhapas Soodvilai, Varanuj ChatsudthipongAbstract:Cyst enlargement in polycystic kidney disease (PKD) involves cAMP-activated proliferation of cyst-lining epithelial cells and transepithelial fluid secretion into the cyst lumen via cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. This study aimed to investigate an inhibitory effect and detailed mechanisms of Steviol and its derivatives on cyst growth using a cyst model in Madin-Darby canine kidney (MDCK) cells. Among 4 Steviol-related compounds tested, Steviol was found to be the most potent at inhibiting MDCK cyst growth. Steviol inhibition of cyst growth was dose-dependent; Steviol (100 microM) reversibly inhibited cyst formation and cyst growth by 72.53.6% and 38.2±8.5%, respectively. Steviol at doses up to 200 microM had no effect on MDCK cell viability, proliferation and apoptosis. However, Steviol acutely inhibited forskolin-stimulated apical chloride current in MDCK epithelia, measured with the Ussing chamber technique, in a dose-dependent manner. Prolonged treatment (24 h) with Steviol (100 microM) also strongly inhibited forskolin-stimulated apical chloride current, in part by reducing CFTR protein expression in MDCK cells. Interestingly, proteasome inhibitor, MG-132, abolished the effect of Steviol on CFTR protein expression. Immunofluorescence studies demonstrated that prolonged treatment (24 h) with Steviol (100 microM) markedly reduced CFTR expression at the plasma membrane. Taken together, the data suggest that Steviol retards MDCK cyst progression in two ways: first by directly inhibiting CFTR chloride channel activity and second by reducing CFTR expression, in part, by promoting proteasomal degradation of CFTR. Steviol and related compounds therefore represent drug candidates for treatment of polycystic kidney disease.
-
Steviol an aglycone of natural sweetener stevioside slows mdck cyst progression by reducing activity and expression of cftr chloride channels
The FASEB Journal, 2012Co-Authors: Chaowalit Yuajit, Chatchai Muanprasat, Varanuj ChatsudthipongAbstract:Pathogenesis of polycystic kidney disease (PKD) involved cAMP-stimulated chloride secretion into cyst lumen. The present study was aimed to investigate an inhibitory effect and detailed mechanisms of Steviol and its derivatives on cyst growth and cyst formation using Madin Darby canine kidney (MDCK) cyst models. Among 4 Steviol-related compounds, Steviol was found to be the most potent compound that inhibited both MDCK cyst growth and formation. Steviol at 100 μM reversibly inhibited cyst growth and cyst formation by 38.3% and 72.4 %, respectively. Steviol at doses up to 200 μM had no cytotoxic effect on MDCK cells. Determined by Ussing chamber experiments, Steviol acutely inhibited forskolin-stimulated apical chloride current in MDCK monolayers by ~40%. Interestingly, prolonged treatment (2–24 hours) with Steviol produced 50–80% inhibition of forskolin-stimulated apical chloride current across MDCK monolayers in dose and time-dependent manners. In addition, treatment with Steviol significantly reduced cy...
-
Interactions of Stevioside and Steviol with Renal Organic Anion Transporters in S2 Cells and Mouse Renal Cortical Slices
Pharmaceutical research, 2005Co-Authors: Chutima Srimaroeng, John B Pritchard, Promsuk Jutabha, Hitoshi Endou, Varanuj ChatsudthipongAbstract:Purpose. Our previous studies have shown that both stevioside and Steviol inhibited transepithelial transport of para-aminohippurate (PAH) in isolated rabbit renal proximal tubules by interfering with organic anion transport system. The current study examined the direct interactions of stevioside and Steviol with specific organic anion transporters. Methods. S2 cells expressing human organic anion transporters (hOAT1, hOAT2, hOAT3, and hOAT4) and an intact renal epithelium were used to determine the inhibitory effect of stevioside and Steviol on organic anion transport. Results. Stevioside at 0.5Y1 mM showed no interaction with any OAT. In contrast, Steviol markedly inhibited substrate uptake in all S2hOAT cells. Steviol had low IC50 values for hOAT1 (11.4 mM) and hOAT3 (36.5 mM) similar to that of probenecid, whereas IC50 values for hOAT2 (1000 mM) and hOAT4 (285 mM) were much higher. Results obtained in mouse renal cortical slices were very similar; that is, stevioside was without inhibitory effect and Steviol was a potent inhibitor of PAH and estrone sulfate (ES) transport. Conclusions . Stevioside has no interaction with human or mouse OATs. In contrast, Steviol interacts directly with human OATs, in particular, hOAT1 and hOAT3, with a potency approximating probenecid, suggesting that the inhibition of OAT-mediated transport by Steviol could alter renal drug clearance.
Jan M C Geuns - One of the best experts on this subject based on the ideXlab platform.
-
Validation of an HPLC method for direct measurement of Steviol equivalents in foods.
Food chemistry, 2015Co-Authors: Uria Bartholomees, Tom Struyf, Olivier Lauwers, Stijn Ceunen, Jan M C GeunsAbstract:Steviol glycosides are intense natural sweeteners used in foods and beverages. Their acceptable daily intake, expressed as Steviol equivalents, is set at 0-4 mg/kg body weight. We report the development and validation of a RP-HPLC method with fluorometric detection of derivatized isoSteviol, formed by acid hydrolysis of Steviol glycosides. DihydroisoSteviol was used as an internal standard. Using this method, the amount of Steviol equivalents in commercial Steviol glycoside mixtures and different foods can be directly quantified. The method was successfully tested on strawberry jam, low-fat milk, soft drink, yogurt and a commercial mixture of Steviol glycosides. Calibration curves were linear between 0.01 and 1.61 mM Steviol equivalents, with a quantification limit of 0.2 nmol. The % RSD of intra-day precision varied between 0.4% and 4%, whereas inter-day precision varied between 0.4% and 5%, for high and medium concentrations, and between 3% and 8% for low concentrations. Accuracy of the analysis varied between 99% and 115%.
-
Stability of Steviol Glycosides in Several Food Matrices
Journal of agricultural and food chemistry, 2012Co-Authors: Etienne Jooken, Jan M C Geuns, Ruis Amery, Tom Struyf, Barbara Duquenne, Boudewijn MeesschaertAbstract:As Steviol glycosides are now allowed as a food additive in the European market, it is important to assess the stability of these Steviol glycosides after they have been added to different food matrices. We analyzed and tested the stability of Steviol glycosides in semiskimmed milk, soy drink, fermented milk drink, ice cream, full-fat and skimmed set yogurt, dry biscuits, and jam. The fat was removed by centrifugation from the dairy and soy drink samples. Proteins were precipitated by the addition of acetonitrile and also removed by centrifugation. Samples of jam were extracted with water. Dry biscuits were extracted with ethanol. The resulting samples were concentrated with solid-phase extraction and analyzed by high-performance liquid chromatography on a C18 stationary phase and a gradient of acetonitrile/aqueous 25 mM phosphoric acid. The accuracy was checked using a standard addition on some samples. For assessing the stability of the Steviol glycosides, samples were stored in conditions relevant to e...
-
Stimulation of Steviol glycoside accumulation in Stevia rebaudiana by red LED light
Journal of plant physiology, 2012Co-Authors: Stijn Ceunen, Stefaan Werbrouck, Jan M C GeunsAbstract:The aim of this study was to determine whether Steviol glycoside accumulation is under phytochrome control. The results indicate that Stevia rebaudiana Bertoni plants grown under short-day conditions showed precocious flowering and stagnation of Steviol glycoside accumulation. Long night interruption by red LED light stimulated and sustained the vegetative growth as well as the accumulation of Steviol glycosides in the leaves. After 7 weeks of treatment, Steviol glycoside content was about two-fold higher in LED-treated plants than in the short-day control group. The effects of red LED light were measured both in a greenhouse and in a phytotron, irrespective of cultivar-specific differences. Therefore, it can be concluded that a mid-night interruption by red LED light during short photoperiods provides an easy and inexpensive method to increase vegetative leaf biomass production with an increased Steviol glycoside yield.
-
UDP-dependent glycosyltransferases involved in the biosynthesis of Steviol glycosides.
Journal of plant physiology, 2011Co-Authors: Amal A.a. Mohamed, Jan M C Geuns, Stijn Ceunen, Wim Van Den Ende, Marc De LeyAbstract:A short-term experiment was designed to measure the transcript levels of downstream genes contributing to the biosynthesis of Steviol glycosides. Stevia rebaudiana plants were subjected to long- and short-day conditions for different time intervals. Samples from both lower and upper leaves were collected. Using quantitative real-time polymerase chain reaction, the transcript levels of three UDP-dependent glycosyltransferases, UGT85C2, UGT74G1 and UGT76G1, were studied. The results were compared with the Steviol glycoside contents measured in the leaves, which were quantified by reversed phase HPLC. In the same daylength condition, Steviol glycoside concentration and the transcript levels of the three UGT genes were higher in upper leaves than in lower leaves. Steviol glycosides accumulated more in plants under short-day conditions. Under these conditions, a highly significant correlation was found between UGT85C2 transcription and total Steviol glycoside accumulation in the upper leaves. This suggests that the glycosylation of Steviol to form Steviolmonoside is the rate-limiting step in the glycosylation pathway of Steviol glycosides. In these upper leaves, a relatively high accumulation of rebaudioside A compared to stevioside was also observed, however, without correlation with the transcription of UGT76G1.
-
Steviol Glucuronide as Excretion Product of Stevioside in Human Volunteers : Lack of Carcinogenic Properties of Steviol Glycosides and Steviol
2008Co-Authors: Jan M C GeunsAbstract:Absorption studies with Caco-2 cell monolayers revealed that Steviol glycosides are barely absorbed by the intestines. Metabolism studies in healthy volunteers have shown that stevioside is completely degraded by bacteria of the colon into Steviol and that part of this Steviol is absorbed and glucuronated in the liver. The glucuronide is released in the blood and filtered by the kidneys into the urine. No accumulation of Steviol glycosides or derivatives has been observed. As mutagenic effects of Steviol were described, a thorough literature study has been made to evaluate possible risks when using Steviol glycosides as a sweetener. The conclusion is that there are no indications that Steviol glycosides used as a sweetener are not safe.
Akiharu Fujino - One of the best experts on this subject based on the ideXlab platform.
-
absorption and metabolism of glycosidic sweeteners of stevia mixture and their aglycone Steviol in rats and humans
Food and Chemical Toxicology, 2003Co-Authors: E Koyama, Yuji Ohori, Osamu Izawa, Kazuyuki Kakegawa, Ke Kitazawa, Norifumi Sakai, Akiharu FujinoAbstract:Stevia mixture, sweeteners extracted from the leaves of Stevia rebaudiana Bertoni, consists mainly of the glycosides of the diterpene derivative Steviol. The aims of this study were to investigate the absorption (in rats) and the hepatic metabolism (in rats and humans) of both stevia mixture and Steviol. Absorption was investigated both in vivo and ex vivo. In ex vivo experiments using the rat everted sac method, no absorption of stevia mixture was observed, but significant absorption of Steviol was noted (equivalent to approximately 70% of the absorption reference- salicylic acid- value). In the in vivo experiment, rats received a single oral administration of either Steviol or stevia mixture; a peak Steviol concentration in plasma was observed 15 min after its oral administration, demonstrating rapid absorption. However, after oral administration of stevia mixture, the Steviol concentration in plasma increased steadily over 8 h, suggesting that stevia mixture components are first degraded and then absorbed as Steviol in the rat intestine. Steviol metabolism in humans and rats was examined by incubating Steviol with liver microsomes from the two species. Oxidative (monohydroxy and dihydroxy) metabolites of Steviol were observed by LC-ESI/MS after incubation with both human and rat liver microsomes. The intrinsic clearance of Steviol in human liver microsomes was 4-times lower than that found in rat liver microsomes. In conclusion, this study suggests that there are no major species differences in Steviol hepatic metabolism between rats and humans. Absorption from the human intestine can be predicted to occur in an analogous manner to that from the rat intestine.
-
in vitro metabolism of the glycosidic sweeteners stevia mixture and enzymatically modified stevia in human intestinal microflora
Food and Chemical Toxicology, 2003Co-Authors: E Koyama, Ken Kitazawa, Yuji Ohori, Osamu Izawa, Kazuyuki Kakegawa, Akiharu Fujino, Michio UiAbstract:Stevia mixture, sweeteners extracted from the leaves of Stevia rebaudiana Bertoni, consists mainly of stevioside and rebaudioside A (glycosides of the diterpene derivative Steviol). The aim of this study was to investigate human intestinal metabolism of stevia mixture and its a-glucose derivative (known in Japan as enzymatically modified stevia) by LC/MS/ESI analysis. Degradation was examined by incubating stevia mixture, enzymatically modified stevia, stevioside, rebaudioside A, a-monoglucosylstevioside, a-monoglucosylrebaudioside A and the aglycone, Steviol with pooled human faecal homogenates (obtained from five healthy volunteers) for 0, 8 and 24 h under anaerobic conditions. Stevia mixture, enzymatically modified stevia, stevioside and rebaudioside A (0.2 mg/ml) were completely eliminated within 24 h, whereas no degradation of Steviol (0.08 and 0.2 mg/ml) appeared to be found during the incubation period. Stevia mixture, stevioside and rebaudioside A appeared to be hydrolyzed to Steviol by human intestinal microflora: this observation is consistent with previous rat metabolism studies. Similarly, enzymatically modified stevia appeared to be metabolized via stevia components and, finally, to Steviol. This study suggests that there are apparently no species differences in intestinal metabolism of stevia mixture between rats and humans. # 2002 Elsevier Science Ltd. All rights reserved.
-
in vitro metabolism of the glycosidic sweeteners stevia mixture and enzymatically modified stevia in human intestinal microflora
Food and Chemical Toxicology, 2003Co-Authors: E Koyama, Yuji Ohori, Osamu Izawa, Kazuyuki Kakegawa, Ke Kitazawa, Akiharu FujinoAbstract:Stevia mixture, sweeteners extracted from the leaves of Stevia rebaudiana Bertoni, consists mainly of stevioside and rebaudioside A (glycosides of the diterpene derivative Steviol). The aim of this study was to investigate human intestinal metabolism of stevia mixture and its alpha-glucose derivative (known in Japan as enzymatically modified stevia) by LC/MS/ESI analysis. Degradation was examined by incubating stevia mixture, enzymatically modified stevia, stevioside, rebaudioside A, alpha-monoglucosylstevioside, alpha-monoglucosylrebaudioside A and the aglycone, Steviol with pooled human faecal homogenates (obtained from five healthy volunteers) for 0, 8 and 24 h under anaerobic conditions. Stevia mixture, enzymatically modified stevia, stevioside and rebaudioside A (0.2 mg/ml) were completely eliminated within 24 h, whereas no degradation of Steviol (0.08 and 0.2 mg/ml) appeared to be found during the incubation period. Stevia mixture, stevioside and rebaudioside A appeared to be hydrolyzed to Steviol by human intestinal microflora: this observation is consistent with previous rat metabolism studies. Similarly, enzymatically modified stevia appeared to be metabolized via stevia components and, finally, to Steviol. This study suggests that there are apparently no species differences in intestinal metabolism of stevia mixture between rats and humans.
Johan Buyse - One of the best experts on this subject based on the ideXlab platform.
-
Identification of Steviol glucuronide in human urine.
Journal of agricultural and food chemistry, 2006Co-Authors: Jan M C Geuns, Frans Compernolle, Johan Buyse, Annelies Vankeirsbilck, Elisabeth H. M. Temme, Suzanne ToppetAbstract:Stevioside (250 mg capsules) was given three times daily to 10 healthy subjects. Steviol glucuronide (Steviol 19-O-beta-D-glucopyranosiduronic acid; MM, 494.58; melting point, 198-199 degrees C) was characterized in the 24 h urine as the only excretion product of oral stevioside by MS, NMR, IR, and UV spectroscopy. This is the first report on the unambiguous identification of Steviol glucuronide in human urine.
-
metabolism of stevioside in pigs and intestinal absorption characteristics of stevioside rebaudioside a and Steviol
Food and Chemical Toxicology, 2003Co-Authors: Jan M C Geuns, Johan Buyse, Patrick Augustijns, Raf Mols, Bert DriessenAbstract:Abstract Stevioside orally administered to pigs was completely converted into Steviol by the bacteria of the colon. However, no stevioside or Steviol could be detected in the blood of the animals, even not after converting Steviol into the (7-methoxycoumarin-4-yl)methyl ester of Steviol, a very sensitive fluorescent derivative with a detection limit of about 50 pg. The intestinal transport characteristics of stevioside, rebaudioside A and Steviol were also studied in the Caco-2 system. Only a minor fraction of stevioside and rebaudioside A was transported through the Caco-2 cell layer giving a P app value of 0.16×10 −6 and 0.11×10 −6 cm/s, respectively. The P app value for the absorptive transport of Steviol was about 38.6×10 −6 cm/s while the P app value for the secretory transport of Steviol was only about 5.32×10 −6 cm/s suggesting carrier-mediated transport. The discrepancy between the relatively high absorptive transport of Steviol and the lack of Steviol in the blood may be explained by the fact that in the Caco-2 study, Steviol is applied as a solution facilitating the uptake, whereas in the colon Steviol probably is adsorbed to the compounds present in the colon of which the contents is being concentrated by withdrawal of water.
-
Effect of stevioside and Steviol on the developing broiler embryos.
Journal of Agricultural and Food Chemistry, 2003Co-Authors: Jan M C Geuns, Veerle Bruggeman, Johan BuyseAbstract:At day 7 of incubation, fertile broiler eggs were injected with different amounts of stevioside and Steviol of 0.08, 0.8, or 4 mg stevioside/egg and 0.025, 0.25, or 1.25 mg Steviol/egg. At hatch (day 21) and 1 week later, not any influence of the different treatments could be found on embryonic mortality, body weight of the hatchlings, deformations (e.g., bone, beak, and head malformations, abnormal feathering, open vent), or abnormal development of the gonads. No stevioside or Steviol could be detected in the blood of the hatchlings. The hatchlings developed normally. It is concluded that prenatal exposure to stevioside and Steviol is not toxic for the chicken embryo. Keywords: Stevia rebaudiana (Bertoni) Bertoni (Compositae); stevioside; Steviol; chicken embryo toxicology
-
Effect of stevioside and Steviol on the developing broiler embryos.
Journal of agricultural and food chemistry, 2003Co-Authors: Jan M C Geuns, Veerle Bruggeman, Johan BuyseAbstract:At day 7 of incubation, fertile broiler eggs were injected with different amounts of stevioside and Steviol of 0.08, 0.8, or 4 mg stevioside/egg and 0.025, 0.25, or 1.25 mg Steviol/egg. At hatch (day 21) and 1 week later, not any influence of the different treatments could be found on embryonic mortality, body weight of the hatchlings, deformations (e.g., bone, beak, and head malformations, abnormal feathering, open vent), or abnormal development of the gonads. No stevioside or Steviol could be detected in the blood of the hatchlings. The hatchlings developed normally. It is concluded that prenatal exposure to stevioside and Steviol is not toxic for the chicken embryo.
-
Metabolism of stevioside by chickens.
Journal of Agricultural and Food Chemistry, 2003Co-Authors: Jan M C Geuns, Vera Maria Barbosa De Moraes, Frans Compernolle, Ramon D. Malheiros, Eddy Decuypere, Johan BuyseAbstract:In intubation experiments (643−1168 mg per animal), most of the stevioside administered to chickens was recovered unchanged in the excreta, and only about 2% was converted into Steviol. Neither stevioside nor Steviol could be found in the blood. In chronic studies (667 mg of stevioside/kg of feed) with laying hens and meat-type chickens, no significant differences were found in feed uptake, weight gain, and feed conversion as the result of stevioside administration. The egg production and egg composition of laying hens were not influenced. Most of the stevioside taken up was found untransformed in the excreta, and about 21.5% or 7.3% was converted to Steviol by meat-type chickens or laying hens, respectively. No stevioside or Steviol could be detected in the blood or in the eggs of the different groups of animals. In anaerobic incubation experiments with chicken excreta, only a 20% conversion of stevioside into Steviol was found. No harmful effects were observed in the chronic stevioside supplementation e...
E Koyama - One of the best experts on this subject based on the ideXlab platform.
-
absorption and metabolism of glycosidic sweeteners of stevia mixture and their aglycone Steviol in rats and humans
Food and Chemical Toxicology, 2003Co-Authors: E Koyama, Yuji Ohori, Osamu Izawa, Kazuyuki Kakegawa, Ke Kitazawa, Norifumi Sakai, Akiharu FujinoAbstract:Stevia mixture, sweeteners extracted from the leaves of Stevia rebaudiana Bertoni, consists mainly of the glycosides of the diterpene derivative Steviol. The aims of this study were to investigate the absorption (in rats) and the hepatic metabolism (in rats and humans) of both stevia mixture and Steviol. Absorption was investigated both in vivo and ex vivo. In ex vivo experiments using the rat everted sac method, no absorption of stevia mixture was observed, but significant absorption of Steviol was noted (equivalent to approximately 70% of the absorption reference- salicylic acid- value). In the in vivo experiment, rats received a single oral administration of either Steviol or stevia mixture; a peak Steviol concentration in plasma was observed 15 min after its oral administration, demonstrating rapid absorption. However, after oral administration of stevia mixture, the Steviol concentration in plasma increased steadily over 8 h, suggesting that stevia mixture components are first degraded and then absorbed as Steviol in the rat intestine. Steviol metabolism in humans and rats was examined by incubating Steviol with liver microsomes from the two species. Oxidative (monohydroxy and dihydroxy) metabolites of Steviol were observed by LC-ESI/MS after incubation with both human and rat liver microsomes. The intrinsic clearance of Steviol in human liver microsomes was 4-times lower than that found in rat liver microsomes. In conclusion, this study suggests that there are no major species differences in Steviol hepatic metabolism between rats and humans. Absorption from the human intestine can be predicted to occur in an analogous manner to that from the rat intestine.
-
in vitro metabolism of the glycosidic sweeteners stevia mixture and enzymatically modified stevia in human intestinal microflora
Food and Chemical Toxicology, 2003Co-Authors: E Koyama, Ken Kitazawa, Yuji Ohori, Osamu Izawa, Kazuyuki Kakegawa, Akiharu Fujino, Michio UiAbstract:Stevia mixture, sweeteners extracted from the leaves of Stevia rebaudiana Bertoni, consists mainly of stevioside and rebaudioside A (glycosides of the diterpene derivative Steviol). The aim of this study was to investigate human intestinal metabolism of stevia mixture and its a-glucose derivative (known in Japan as enzymatically modified stevia) by LC/MS/ESI analysis. Degradation was examined by incubating stevia mixture, enzymatically modified stevia, stevioside, rebaudioside A, a-monoglucosylstevioside, a-monoglucosylrebaudioside A and the aglycone, Steviol with pooled human faecal homogenates (obtained from five healthy volunteers) for 0, 8 and 24 h under anaerobic conditions. Stevia mixture, enzymatically modified stevia, stevioside and rebaudioside A (0.2 mg/ml) were completely eliminated within 24 h, whereas no degradation of Steviol (0.08 and 0.2 mg/ml) appeared to be found during the incubation period. Stevia mixture, stevioside and rebaudioside A appeared to be hydrolyzed to Steviol by human intestinal microflora: this observation is consistent with previous rat metabolism studies. Similarly, enzymatically modified stevia appeared to be metabolized via stevia components and, finally, to Steviol. This study suggests that there are apparently no species differences in intestinal metabolism of stevia mixture between rats and humans. # 2002 Elsevier Science Ltd. All rights reserved.
-
in vitro metabolism of the glycosidic sweeteners stevia mixture and enzymatically modified stevia in human intestinal microflora
Food and Chemical Toxicology, 2003Co-Authors: E Koyama, Yuji Ohori, Osamu Izawa, Kazuyuki Kakegawa, Ke Kitazawa, Akiharu FujinoAbstract:Stevia mixture, sweeteners extracted from the leaves of Stevia rebaudiana Bertoni, consists mainly of stevioside and rebaudioside A (glycosides of the diterpene derivative Steviol). The aim of this study was to investigate human intestinal metabolism of stevia mixture and its alpha-glucose derivative (known in Japan as enzymatically modified stevia) by LC/MS/ESI analysis. Degradation was examined by incubating stevia mixture, enzymatically modified stevia, stevioside, rebaudioside A, alpha-monoglucosylstevioside, alpha-monoglucosylrebaudioside A and the aglycone, Steviol with pooled human faecal homogenates (obtained from five healthy volunteers) for 0, 8 and 24 h under anaerobic conditions. Stevia mixture, enzymatically modified stevia, stevioside and rebaudioside A (0.2 mg/ml) were completely eliminated within 24 h, whereas no degradation of Steviol (0.08 and 0.2 mg/ml) appeared to be found during the incubation period. Stevia mixture, stevioside and rebaudioside A appeared to be hydrolyzed to Steviol by human intestinal microflora: this observation is consistent with previous rat metabolism studies. Similarly, enzymatically modified stevia appeared to be metabolized via stevia components and, finally, to Steviol. This study suggests that there are apparently no species differences in intestinal metabolism of stevia mixture between rats and humans.
