Analysis of anti-rotavirus activity of extract from Stevia rebaudiana.
Takahashi K, Matsuda M, Ohashi K, Taniguchi K, Nakagomi O, Abe Y, Mori S, Sato N, Okutani K, Shigeta S Department of Microbiology, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, 960-1295, Fukushima-shi, Japan
Antiviral Res 2001 Jan;49(1):15-24
Anti-human rotavirus (HRV) activity of hot water extracts from Stevia rebaudiana (SE) was examined. SE inhibited the replication of all four serotypes of HRV in vitro. This inhibitory effect of SE was not reduced on the prior exposure of SE to HCl for 30 min at pH 2. Binding assay with radiolabeled purified viruses indicated that the inhibitory mechanism of SE is the blockade of virus binding. The SE inhibited the binding of anti-VP7 monoclonal antibody to HRV-infected MA104 cells. The inhibitory components of SE were found to be heterogeneous anionic polysaccharides with different ion charges. The component analyses suggested that the purified fraction named as Stevian with the highest inhibitory activity consists of the anionic polysaccharide with molecular weight of 9800, and contains Ser and Ala as amino acids. Analyses of sugar residues suggest uronic acid(s) as sugar components. It did not contain amino and neutral sugars and sulfate residues. These findings suggest that SE may bind to 37 kD VP7 and interfere with the binding of VP7 to the cellular receptors by steric hindrance, which results in the blockade of the virus attachment to cells.
A double-blind placebo-controlled study of the effectiveness and tolerability of oral stevioside in human hypertension.
Chan P, Tomlinson B, Chen YJ, Liu JC, Hsieh MH, Cheng JT Division of Cardiovascular Medicine, Taipei Medical College and affiliated Taipei Wan Fang Hospital, Taiwan.
Br J Clin Pharmacol 2000 Sep;50(3):215-20
AIMS: Stevioside is a natural plant glycoside isolated from the plant Stevia rebaudiana which has been commercialized as a sweetener in Japan for more than 20 years. Previous animal studies have shown that stevioside has an antihypertensive effect. This study was to designed to evaluate the effect of stevioside in human hypertension. METHODS: A multicentre, randomized, double-blind, placebo-controlled study was undertaken. This study group consisted of 106 Chinese hypertensive subjects with diastolic blood pressure between 95 and 110 mmHg and ages ranging from 28 to 75 years with 60 subjects (men 34, women 26; mean +/- s.d., 54.1+/-3.8 years) allocated to active treatment and 46 (men 19, women 27; mean +/- s.d., 53.7+/-4.1 years) to placebo treatment. Each subject was given capsules containing stevioside (250 mg) or placebo thrice daily and followed-up at monthly intervals for 1 year. RESULTS: After 3 months, the systolic and diastolic blood pressure of the stevioside group decreased significantly (systolic: 166.0+/-9.4-152.6+/-6.8 mmHg; diastolic: 104.7 +/- 5.2-90.3+/-3.6 mmHg, P<0.05), and the effect persisted during the whole year. Blood biochemistry parameters including lipid and glucose showed no significant changes. No significant adverse effect was observed and quality of life assessment showed no deterioration. CONCLUSIONS: This study shows that oral stevioside is a well tolerated and effective modality that may be considered as an alternative or supplementary therapy for patients with hypertension.
Stevioside acts directly on pancreatic beta cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity.
Jeppesen PB, Gregersen S, Poulsen CR, Hermansen K Department of Endocrinology and Metabolism, Aarhus University Hospital, Denmark.
Metabolism 2000 Feb;49(2):208-14
The natural sweetener stevioside, which is found in the plant Stevia rebaudiana Bertoni, has been used for many years in the treatment of diabetes among Indians in Paraguay and Brazil. However, the mechanism for the blood glucose-lowering effect remains unknown. To elucidate the impact of stevioside and its aglucon steviol on insulin release from normal mouse islets and the beta-cell line INS-1 were used. Both stevioside and steviol (1 nmol/L to 1 mmol/L) dose-dependently enhanced insulin secretion from incubated mouse islets in the presence of 16.7 mmol/L glucose (P < .05). The insulinotropic effects of stevioside and steviol were critically dependent on the prevailing glucose concentration, ie, stevioside (1 mmol/L) and steviol (1 micromol/L) only potentiated insulin secretion at or above 8.3 mmol/L glucose (P < .05). Interestingly, the insulinotropic effects of both stevioside and steviol were preserved in the absence of extracellular Ca2+. During perifusion of islets, stevioside (1 mmol/L) and steviol (1 micromol/L) had a long-lasting and apparently reversible insulinotropic effect in the presence of 16.7 mmol/L glucose (P < .05). To determine if stevioside and steviol act directly on beta cells, the effects on INS-1 cells were also investigated. Stevioside and steviol both potentiated insulin secretion from INS-1 cells (P < .05). Neither stevioside (1 to 100 micromol/L) nor steviol (10 nmol/L to 10 micromol/L) influenced the plasma membrane K+ adenosine triphosphate ((K+)ATP)-sensitive channel activity, nor did they alter cyclic adenosine monophosphate (cAMP) levels in islets. In conclusion, stevioside and steviol stimulate insulin secretion via a direct action on beta cells. The results indicate that the compounds may have a potential role as antihyperglycemic agents in the treatment of type 2 diabetes mellitus.
Measurement of the relative sweetness of stevia extract, aspartame and cyclamate/saccharin blend as compared to sucrose at different concentrations.
Cardello HM, Da Silva MA, Damasio MH Department of Food and Nutrition, FCF-UNESP, Araraquara, SP, Brazil. firstname.lastname@example.org
Plant Foods Hum Nutr 1999;54(2):119-30
Special diets are used to mitigate many human diseases. When these diets require changes in carbohydrate content, then sweetness becomes an important characteristic. The range of low-calorie sweeteners available to the food industry is expanding. It is essential to have an exact knowledge of the relative sweetness of various sweeteners in relation to different sucrose concentrations. The objective of this study was to determine the variation on the relative sweetness of aspartame (APM), stevia [Stevia rebaudiana (Bert.) Bertoni] leaf extract (SrB) and the mixture cyclamate/saccharin--two parts of cyclamate and one part of saccharin--(C/S) with the increase in their concentrations, and in neutral and acid pH in equisweet concentration to 10% sucrose, using magnitude estimation. Sweetness equivalence of SrB in relation to sucrose concentrations of 20% or higher and of APM and C/S to sucrose concentrations of 40% or higher could not be determined, because a bitter taste predominated. The potency of all sweeteners decreased as the level of sweetner increased. In equi-sweet concentration of sucrose at 10%, with pH 7.0 and pH 3.0, the potency was practically the same for all sweeteners evaluated.
The effect of stevioside on blood pressure and plasma catecholamines in spontaneously hypertensive rats.
Chan P, Xu DY, Liu JC, Chen YJ, Tomlinson B, Huang WP, Cheng JT Division of Cardiovascular Medicine, Taipei Medical College Hospital and affiliated Taipei Wan Fang Hospital, Taiwan, ROC.
Life Sci 1998;63(19):1679-84
Stevioside is a sweet-tasting glycoside, composed of stevia, a diterpenic carboxylic alcohol with three glucose molecules, mainly used as a substitute for non-alcoholic sweetener. It has previously been shown to reduce blood pressure in studies in animals and human. The effect of intravenous stevioside on the blood pressure was studied in spontaneously hypertensive rats (SHR). The hypotensive effect on both systolic and diastolic blood pressure was dose-dependent for intravenous doses of 50, 100 and 200 mg/kg in conscious SHR. The maximum reductions in systolic and diastolic blood pressure were 31.4 +/- 4.2% and 40.8 +/- 5.6% (mean +/- SEM) respectively and the hypotensive effect lasted for more than 60 min with a dose of 200 mg/kg. Serum dopamine, norepinephrine and epinephrine levels were not changed significantly 60 min after intravenous injection of stevioside 100 mg/kg in anesthetized SHR. The present data show that stevioside given intravenously to conscious SHR was effective in blood pressure reduction and there was no change in serum catecholamines in anaesthetized animals with this natural compound.
Steviol and steviol-glycoside: glucosyltransferase activities in Stevia rebaudiana Bertoni--purification and partial characterization.
Shibata H, Sawa Y, Oka T, Sonoke S, Kim KK, Yoshioka M Faculty of Agriculture, Shimane University, Japan.
Arch Biochem Biophys 1995 Aug 20;321(2):390-6
The leaves of Stevia rebaudiana Bertoni contain sweet compounds which are glycosides of diterpene derivative steviol (ent-13-hydroxykaur-16-en-19-oic acid). Its main constituents are stevioside (triglucosylated steviol; 13-O-beta-sophorosyl-19-O-beta-glucosyl-steviol) and rebaudioside-A (tetraglucosylated steviol; 2'-O-beta-glucosyl-13-O-beta-sophorosyl-19-O-beta-glucosyl-stev iol). From the extracts of S. rebaudiana Bertoni, two glucosyltransferases (GTases I and IIB) acting on steviol and steviol-glycosides were isolated, and another distinct activity (GTase IIA) acting on steviol was detected. Purified GTase I (subunit M(r) 24,600) catalyzed glucose transfer from UDP-glucose to steviol and steviolmonoside (steviol-13-O-glucopyranoside), but not to other steviol-glycosides. Apparent Km values were 71.4 microM for steviol and 360 microM for UDP-glucose. GTase IIB (subunit M(r) 30,700) showed a broad substrate specificity, acting on steviol, steviolmonoside, steviolbioside (13-O-beta-sophorosyl-steviol), and stevioside. Apparent Km values were 182 microM for steviol, 44 microM for steviolbioside, 95 microM for stevioside, and 385 microM for UDP-glucose. The two enzymes had a similar optimum pH at 6.5. They also acted effectively on ubiquitous flavonol aglycones, quercetin, and kaempferol and utilized kaempferol at a higher rate than steviol and steviol-glycosides. The apparent Km values of GTase I and IIB for kaempferol were 12 and 31 microM, respectively.
Chronic administration of aqueous extract of Stevia rebaudiana in rats: renal effects.
Melis MS Departamento de Biologia, Faculdade de Filosofia, Ciencias e Letras Universidade de Sao Paulo, Ribeirao Preto, Brazil.
J Ethnopharmacol 1995 Jul 28;47(3):129-34
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.
Influence of stevioside on hepatic glycogen levels in fasted rats.
Hubler MO, Bracht A, Kelmer-Bracht AM Laboratory of Liver Metabolism, University of Maringa, Brazil.
Res Commun Chem Pathol Pharmacol 1994 Apr;84(1):111-8
The influence of stevioside, the sweet glycoside of Stevia rebaudiana leaves, on the glycogen levels of fasted rats was investigated. In one set of experiments, single doses of stevioside (200 mumol) or steviol (200 mumol) were given orally to 24-hours fasted rats, either alone or simultaneously with fructose. Under these conditions both stevioside and steviol increased the initial glycogen deposition in the liver. In another set of experiments, stevioside was given to the rats in the drinking water at the beginning of the fasting periods (5:00 p.m.) of 24 and 48 hours. Two different concentrations were given, 1.0 and 2.0 mM. Increased hepatic glycogen levels were found at 48 hours with stevioside (1.0 mM) and at 24 hours with stevioside (2.0 mM). Steviol had no effect on hepatic glycogen levels when given in the drinking water. It can be concluded that stevioside exerts a stimulatory action on hepatic glycogen synthesis under gluconeogenic conditions.
Evaluation of the cariogenic potential of the intense natural sweeteners stevioside and rebaudioside A.
Das S, Das AK, Murphy RA, Punwani IC, Nasution MP, Kinghorn AD Department of Pediatric Dentistry, College of Dentistry, University of Illinois, Chicago 60612.
Caries Res 1992;26(5):363-6
Stevioside and rebaudioside A, two intense natural sweeteners, that are constituents of the South American plant Stevia rebaudiana, were tested for cariogenicity in albino Sprague-Dawley rats. Sixty rat pups colonized with Streptococcus sobrinus were divided into four groups and fed stevioside, rebaudioside A or sucrose added to basal diet 2000 as follows: group 1, 30% sucrose; group 2, 0.5% stevioside; group 3, 0.5% rebaudioside A, and group 4, no addition. All four groups were sacrificed after 5 weeks. S. sobrinus counts were made and caries was evaluated according to Keyes' technique. There were no differences in food and water intake and weight gains between the four groups. There were significant differences in sulcal caries scores (p < 0.02) and S. sobrinus counts (p < 0.05) between group 1 and the other three groups. There were no significant differences between the stevioside, rebaudioside A and no-addition groups. It was concluded that neither stevioside nor rebaudioside A is cariogenic under the conditions of this study.