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At least 19 recordsLinked to original sources

PubMed2003

In vitro metabolism of the glycosidic sweeteners, stevia mixture and enzymatically modified stevia in human intestinal microflora.

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.

Adult↗

PubMed2005

[Method of component assay of alpha-glucosyltransferase-treated stevia (enzymatically modified stevia) products using enzymatic hydrolysis].

We have developed an analytical method for components of alpha-glucosyltransferase-treated stevia, a food additive product. Suitable conditions to separate additional sugar from alpha-glucosyltransferase-treated stevia by using glucoamylase were found (55 degrees C for 3 hr with 250 U of glucoamylase in 10 mL of reaction solution). By solid-phase extraction using a C18 cartridge column, polysaccharides were excluded from the sample, and the glycosides and sugar obtained after hydrolysis with glucoamylase were separated on another C18 cartridge column. The glycosides and sugar contents were determined by HPLC. By this method, additional sugar was detected in all of three product samples tested and the sugar was glucose. The contents of glucose and total glycosides (minus unreacted glycoside) were 25-42% and 35.7-52.5%, respectively. In alpha-glucosyltransferase-treated stevia, the sum of total glycosides and glucose amounted to 77.5-80.4% of the total and their recoveries from samples from which polysaccharide had been excluded by C18 cartridge column processing were over 85%. The contents of alpha-glucosyltransferase-treated stevia obtained by multiplying the sugar content by the coefficient (0.9) for hydrolysis and converting on dry weight basis were all over 80.0% and met the standard set by the Japan Food Additives Association.

Carbohydrates↗

PubMed2005

Interaction effect between phosphorus and zinc on their availability in soil in relation to their contents in stevia (Stevia rebaudiana).

A greenhouse experiment was conducted at the Indian Institute of Horticultural Research (IIHR), Bangalore to study the interaction effect between phosphorus and zinc on their availability in soil in relation to their contents in stevia (Stevia rebaudiana). The results show that the amount of available P and Zn content in soil has been found to increase initially and, thereafter, the amount of the same decreased with the progress of plant growth up to 60 days irrespective of treatments. The amount of P and Zn in soils showed an increase with their separate applications either as soil or foliar spray while that of the same value significantly decreased both in soils and plants due to their combined applications, suggesting a mutual antagonistic effect between Zn and P affecting each other's availability in soil and content in the stevia plant.

Drug Interactions↗

PubMed2005

Interaction between phosphorus and zinc on the biomass yield and yield attributes of the medicinal plant stevia (Stevia rebaudiana).

A greenhouse experiment was conducted at the Indian Institute of Horticultural Research (IIHR), Bangalore to study the interaction effect between phosphorus (P) and zinc (Zn) on the yield and yield attributes of the medicinal plant stevia. The results show that the yield and yield attributes have been found to be significantly affected by different treatments. The total yield in terms of biomass production has been increased significantly with the application of Zn and P in different combinations and methods, being highest (23.34 g fresh biomass) in the treatment where Zn was applied as both soil (10 kg ZnSO4/ha) and foliar spray (0.2% ZnSO4). The results also envisaged that the different yield attributes viz. height, total number of branches, and number of leaves per plant have been found to be varied with treatments, being highest in the treatment where Zn was applied as both soil and foliar spray without the application of P. The results further indicated that the yield and yield attributes of stevia have been found to be decreased in the treatment where Zn was applied as both soil and foliar spray along with P suggesting an antagonistic effect between Zn and P.

Biomass↗

PubMed1996

A crude extract of Stevia rebaudiana increases the renal plasma flow of normal and hypertensive rats.

The effect of S. rebaudiana extract on renal function was evaluated in normotensive and in experimental renal hypertensive rats (GII) using clearance techniques. Experiments were performed on male Wistar rats weighing 300-330 g (10 animals per group). Goldblatt GII experimental hypertension was induced by placing a silver clip with an internal gap of 0.25 mm around the left renal artery under ether anesthesia. The contralateral kidney was left untouched. Stevia was administered 10-12 weeks after clipping. Oral-administration of Stevia extract, corresponding to 2.67 g dry leaves/day for 30 days, resulted in a significant decrease in mean arterial pressure in both the normo-(N) and hypertensive rats (H) (N rats: 113 +/- 3.0 mmHg in the control (C) group vs 69.5 +/- 4.0 mmHg in the Stevia (S) group; H rats: 155 +/- 3.0 mmHg in C vs 108 +/- 4.0 mmHg in S; P < 0.05). Glomerular filtration rate was constant in the N rats and increased significantly in the H rats after Stevia treatment 16.47 +/- 1.29 vs 14.2 +/- 1.33 ml min-1 kg-1 in the C and S groups, respectively, P < 0.05). Normo- and hypertensive rats presented an increase in renal plasma flow following oral Stevia administration (N rats: 16.4 +/- 3.10 ml min-1 kg-1 in the C group vs 33.3 +/- 3.20 ml min-1 kg-1 in the S group. P < 0.05; H rats: 19.30 +/- 2.45 ml min-1 kg-1 in the C group vs 37.0 +/- 3.93 ml min-1 kg-1 in the S group, P < 0.05). Stevia administration provoked an increase in urinary flow in both N and H animals (1.37 +/- 0.08% vs 2.32 +/- 0.11%, P < 0.05 and 1.47 +/- 0.07% vs 2.96 +/- 0.13%, P < 0.05 in N and H rats, respectively). Sodium excretion increased in N and H animals after Stevia treatment (N rats: 0.61 +/- 0.07% in the C group vs 1.55 +/- 0.20% in the S group, P < 0.05; H rats: 0.70 +/- 0.10% in the C group vs 2.22 +/- 0.45% in the S group, P < 0.05). These results are consistent with impairment of a renal autoregulation mechanism in this hypertensive model after Stevia administration. In conclusion, it was shown that Stevia extract, at doses higher than used for sweetening purposes, is a vasodilator agent in normo- and hypertensive animals.

Animals↗

PubMed2026

Acute Stevia Consumption does not Alter Endocrine Responses in Individuals with Normal Weight, Overweight, and Type 2 Diabetes Mellitus.

BACKGROUND: Stevia is a plant-based non-nutritive sweetener. Acute effects of stevia ingestion on glycemia and hormonal responses have not been fully investigated. OBJECTIVE: This objective of this study was to evaluate the acute effects of beverages containing stevia alone and in combination with glucose on glycemic, hormonal, and appetite responses. METHODS: This study evaluated three cohorts of n=23 individuals with either normal weight (NW), overweight (OW), or type 2 diabetes mellitus (T2DM) for which each individual completed four test conditions in a randomized sequence crossover study design. The four test conditions were beverages containing stevia (75.6 mg steviol equivalents), water, glucose (30 g), and stevia+glucose (30 g glucose+75.6 mg steviol equivalents). Blood samples were collected before and for 180 min after beverage consumption. Assessments included net area under the curve (niAUC) and incremental maximal concentration values for plasma glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1, glucagon, and PYY. Appetite was assessed with visual-analog scale questions and energy consumption during an ad libitum meal. RESULTS: Responses to the stevia beverage did not differ significantly from those for water alone, and stevia + glucose did not differ significantly from glucose alone for any of the three groups. CONCLUSION: Acute stevia consumption did not materially alter responses for glycemia or hormones involved in glucose and appetite regulation, appetite ratings, or energy intake at a subsequent meal. Clinical Trial Registry number and website where it was obtained: Clinical Trials.gov Identifier: NCT05287906. Study Details | NCT05287906 | A Trial to Assess Steviol Glycosides on Acute Appetite Hormone Release | ClinicalTrials.gov.

Appetite↗

PubMed2003

Absorption and metabolism of glycosidic sweeteners of stevia mixture and their aglycone, steviol, in rats and humans.

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.

Administration, Oral↗

PubMedDate not supplied

Joint effect of commercial preparations of Stevia rebaudiana Bertoni and sodium monoketocholate on glycemia in mice.

A study was made of the combined effect of two commercial products of Stevia rebaudiana Bertoni and sodium monoketocholate (mkc) on blood glucose concentration in mice. One group of animals was treated four days with mkc, 4 mg/kg, s.c., second with 200 mg/kg, i.p., of Stevita (Stevita Co, INC, Arlington, Texas) (stevia), third with 20 mg/kg, i.p., of Clear Steviosides Liquid (Stevita Co, INC, Herbal supplement, Brazil) (stevioside), fourth with the combination of stevia and mkc, and the fifth with stevisode and mkc. Blood glucose concentration was measured before treatment, after the first and fourth dose, as well as after subjecting animals to glucose-tolerance test (500 mg/kg, p.o.) or provoking glycemia by injecting adrenaline (0.2 mg/kg, s.c.). It was found that one dose of stevioside combined with mkc caused a significant increase of glycemia with respect of mkc alone and control (10.80:7.90:8.01). However, when repeated four days, the same pretreatment resulted in a significant decrease of glycemia compared with single-dose pretreatment (10.80:7.20). The increase in glycemia with the mice that received four doses of stevioside and mkc and then were subjected to glucose-tolerance test was significantly lower compared to that in mice that were pretreated four days only with mkc before receiving glucose (6.33:7.80). Analogous difference was observed between the animals given mkc alone and mkc plus stevioside after injecting adrenaline (13.33:10.54). As for the interaction of mkc and stevia it was found that the combined pretreatment yielded lower values of glycemia compared with that measured after treatment with stevia alone (6.40:7.82).

Adrenergic alpha-Agonists↗

PubMedDate not supplied

Glucose concentration in the blood of intact and alloxan-treated mice after pretreatment with commercial preparations of Stevia rebaudiana (Bertoni).

The study was concerned with the effect of mice pretreatment with two commercial products of Stevia rebaudiana Bertoni on the blood glucose concentration. One group of mice was pretreated four days with 200 mg/kg of Stevita (Stevita Co, INC, Arlington Texas) (stevia) and the other with 20 mg/kg of Clear Steviosides liquid (Stevita Co, INC, Herbal supplement, Brazil) (stevioside), whereas the animals of control group received at the same time physiological solution. Blood glucose concentration was measured before pretreatment and four days after that. The changes in glucose level were provoked by glucose-tolerance test (500 mg/kg, p.o.) and subcutaneous injection of adrenaline (0.2 mg/kg). The same procedure of measuring blood glucose was applied on the mice with alloxan-induced diabetes mellitus (two doses of 100 mg/kg with a 24-hour interval). Blood glucose levels in mice pretreated with stevia and stevioside were lower compared with control (7.82:6.82:8.01). Also, a smaller increase in this parameter compared to control was registered with pretreated mice in the glucose-tolerance test, pretreatment with stevioside being again more effective (8.68:6.36:5.82). Pretreatment with stevioside caused no significant increase in blood glucose concentration after administering adrenaline, which was not the case with the animals pretreated with stevia and control. Pretreatment with stevia, and to a greater extent with stevioside, protected test animals from the toxic action of alloxan compared with controls.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

A phytochemical screening procedure for sweet ent-kaurene glycosides in the genus Stevia.

Altogether, 110 species of the genus Stevia, comprising both herbarium and fresh leaf samples, were screened for the presence of sweet ent-kaurene glycosides, using a combination of tlc and hplc, followed by gc/ms. Stevioside and rebaudiosides A and C were detected in a Stevia rebaudiana herbarium specimen collected in Paraguay in 1919, and stevioside was observed as a constituent of a Stevia phlebophylla herbarium specimen collected in Mexico in 1889. Steviol glycosides were not detected in any of the other 108 Stevia species studied. The phytochemical results obtained in this study are correlated with those of preliminary organoleptic tests on the sweetness of these Stevia samples, and the chemotaxonomic implications of the present findings are discussed.

Chemical Phenomena↗

PubMed2002

[Genotoxicity studies of stevia extract and steviol by the comet assay].

The genotoxicity of steviol, a metabolite of stevia extract, was evaluated for its genotoxic potential using the comet assay. In an in vitro study, steviol at 62.5, 125, 250, and 500 micrograms/ml did not damage the nuclear DNA of TK6 and WTK1 cells in the presence and absence of S9 mix. In vivo studies of steviol were conducted by two independent organizations. Mice were sacrificed 3 and 24 hr after one oral administration of steviol at 250, 500, 1000, and 2000 mg/kg. DNA damage in multiple mouse organs was measured by the comet assay as modified by us. After oral treatment, stomach, colon, liver, kidney and testis DNA were not damaged. The in vivo genotoxicity of stevia extract was also evaluated for its genotoxic potential using the comet assay. Mice were sacrificed 3 and 24 hr after oral administration of stevia extract at 250, 500, 1000, and 2000 mg/kg. Stomach, colon and liver DNA were not damaged. As all studies showed negative responses, stevia extract and steviol are concluded to not have DNA-damaging activity in cultured cells and mouse organs.

Animals↗

PubMed1995

Chronic administration of aqueous extract of Stevia rebaudiana in rats: renal effects.

The effects of administration of Stevia rebaudiana extracts for 20, 40 and 60 days on renal function and mean arterial pressure in normal Wistar rats were evaluated. Results showed that the Stevia rebaudiana treated rats group for 20 days did not significantly differ from the control group. Chronic administration of a crude extract for 40 and 60 days induced hypotension, diuresis and natriuresis with glomerular filtration rate (GFR) constant. An increase of the renal plasma flow (RPF) was exclusively observed for the group treated for 60 days. The results suggests that oral administration to rats of an aqueous extract of Stevia dried leaves induce systemic and renal vasodilation, causing hypotension, diuresis and natriuresis.

Administration, Oral↗

PubMed1999

Effects of chronic administration of Stevia rebaudiana on fertility in rats.

A study conducted on prepubertal male rats showed that chronic administration (60 days) of a Stevia rebaudiana aqueous extract produced a decrease in final weight of testis, seminal vesicle and cauda epididymidis. In addition, the fructose content of the accessory sex glands and the epididymal sperm concentration are decreased. Stevia treatment tended to decrease the plasma testosterone level, probably by a putative affinity of glycosides of extract for a certain androgen receptor, and no alteration occurred in luteinizing hormone level. These data are consistent with the possibility that Stevia extracts may decrease the fertility of male rats.

Animals↗

PubMed2006

Spatial organisation of four enzymes from Stevia rebaudiana that are involved in steviol glycoside synthesis.

The sweet steviol glycosides found in the leaves of Stevia rebaudiana Bert. are derived from the diterpene steviol which is produced from a branch of the gibberellic acid (GA) biosynthetic pathway. An understanding of the spatial organisation of the two pathways including subcellular compartmentation provides important insight for the metabolic engineering of steviol glycosides as well as other secondary metabolites in plants. The final step of GA biosynthesis, before the branch point for steviol production, is the formation of (-)-kaurenoic acid from (-)-kaurene, catalysed by kaurene oxidase (KO). Downstream of this, the first committed step in steviol glycoside synthesis is the hydroxylation of kaurenoic acid to form steviol which is then sequentially glucosylated by a series of UDP-glucosyltransferases (UGTs) to produce the variety of steviol glycosides. The subcellular location of KO and three of the UGTs involved in steviol glycoside biosynthesis was investigated by expression of GFP fusions and cell fractionation which revealed KO to be associated with the endoplasmic reticulum and the UGTs in the cytoplasm. It has also been shown by expressing the Stevia UGTs in Arabidopsis that the pathway can be partially reconstituted by recruitment of a native Arabidopsis glucosyltransferase.

Arabidopsis↗

PubMed2006

Characterisation of Stevia rebaudiana by comprehensive two-dimensional liquid chromatography time-of-flight mass spectrometry.

Comprehensive two-dimensional liquid chromatography (LC x LC) connected on-line to electrospray ionisation time-of-flight mass spectrometry (ESI-TOF-MS) was employed for analysis of aqueous extract of Stevia rebaudiana. Different combinations of strong cation-exchange (SCX), amino (NH2), and octadecyl siloxane (C18) stationary phases were tested in the separation of all nine known sweet Stevia glycosides. A combination of C18 as the first-dimension column and NH2 as the second-dimension column fully separated all the glycosides from the matrix. The method proved to be quantitative and repeatable. The limit of detection (S/N=3) for stevioside, a widely used natural sweetener, was 43.4 ng/g in dry leaves. The RSD for retention times was <0.1% and that of peak areas 4.5%.

Chromatography, Liquid↗

PubMed2003

Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora.

Stevia rebaudiana standardized extracts (SSEs) are used as natural sweeteners or dietary supplements in different countries for their content of stevioside or rebaudioside A. These compounds possess up to 250 times the sweetness intensity of sucrose, and they are noncaloric and noncariogenic sweeteners. The aim of this study was to investigate the in vitro transformation of stevioside and rebaudioside A after incubation with human microflora, the influence of these sweeteners on human microbial fecal community and which specific groups metabolize preferentially stevioside and rebaudioside A. The experiments were carried out under strict anaerobic conditions in batch cultures inoculated with mixed fecal bacteria from volunteers. The hydrolysis was monitored by HPLC coupled to photodiode array and mass spectrometric detectors. Isolated bacterial strains from fecal materials incubated in selective broths were added to stevioside and rebaudioside A. These sweeteners were completely hydrolyzed to their aglycon steviol in 10 and 24 h, respectively. Interestingly, the human intestinal microflora was not able to degrade steviol. Furthermore, stevioside and rebaudioside A did not significantly influence the composition of fecal cultures; among the selected intestinal groups, bacteroides were the most efficient in hydrolyzing Stevia sweeteners to steviol.

Adult↗

PubMed2006

Inhibitory effects of hot water extract of the Stevia stem on the contractile response of the smooth muscle of the guinea pig ileum.

The effects of a hot water extract of the stem of Stevia rebaudiana on the smooth muscle of isolated guinea pig ileum were investigated. The butyl alcohol layer of the extract antagonized the contractions of the isolated guinea pig ileum induced by histamine (1 x 10(-5) M) and acetylcholine (1 x 10(-5) M) in a concentration-dependent manner. The butyl alcohol layer of the extract also showed inhibition of CaCl(2) (1 x 10(-3)-3.8 x 10(-1) M)-induced contractions. The antagonism of the extract was considered to be non-specific, but this action might be related to an influx of extracellular Ca(2+). With column chromatography preparation, the active component was assumed to be as stevioside. The antagonistic effects exerted by the stem extract of Stevia rebaudiana contributed to the gastroprotective activity of the extract in animals fed dietary histamine.

Acetylcholine↗

PubMed1992

Stevisalioside A, a novel bitter-tasting ent-atisene glycoside from the roots of Stevia salicifolia.

A new acetylated ent-atisene glycoside, stevisalioside A [1], has been isolated as a bitter-tasting principle from Stevia salicifolia roots. The structure was established by the interpretation of spectral data, with the nmr assignments of this compound being based on 1H-1H COSY, 1H-13C HETCOR, and selective INEPT experiments. A rearrangement product 4 of the aglycone moiety obtained by alkaline hydrolysis supported the structure of 1. This is the first report of the occurrence of an atisane-type diterpene from the genus Stevia.

Carbohydrate Sequence↗