stevioside and Body-Weight

Stevia rebaudiana Bertoni possesses various medicinal and food industrial applications. This study is the first to explore the effect of the cytokinins meta-Topolin (mT; 6-(3-hydroxybenzylamino) purine), zeatin, kinetin, and BAP (6-benzylaminopurine) at concentrations of 0 (control), 5, 10, and 15 µM on shoot multiplication, as well as stevioside, rebaudioside A, phenolic acid, and flavonoid content in bioreactor cultures. The highest number of shoots (23.4 per explant) was obtained in the medium containing 5 μM of mT. However, 15 μM of mT was superior for fresh biomass production and dry biomass accumulation. Reversed-phase (RP)-HPLC analysis showed a beneficial effect of 5 μM mT on stevioside (11.43 mg/g dry weight [DW]) and rebaudioside A (10.74 mg/g DW) biosynthesis. In all conditions, the ratio of rebaudioside A/stevioside ranged from 0.75 to 1.12. The phenolic acids chlorogenic, neochlorogenic, isochlorogenic A, and rosmarinic were confirmed in the stevia extracts, as were the flavonoids isoquercetin, and quercitrin. The highest accumulations of chlorogenic and neochlorogenic acids and flavonoids were observed in shoot tissues derived from 5 µM mT, whereas 5 µM of BAP stimulated biosynthesis of chlorogenic, isochlorogenic A, and rosmarinic acids. This is the first report on the use of mT-cytokinin showing high potential in stevia cultures.

Topics: Bioreactors; Body Weight; Flavonoids; Stevia

Topics: Animals; Body Weight; Cognition; Male; Non-Nutritive Sweeteners; Rats; Rats, Sprague-Dawley; Stevia; Sweetening Agents

Sixty male broiler chickens fed a diet supplemented with 130 mg/kg stevioside (S group) or an unsupplemented diet (C group) from day 1 of age onwards. On day 21 of age, ten birds from either the S (SH) or C (CH) group were injected subcutaneously with 100 μg human serum albumin (HSA) and ten others from either S (SP) or C (CP) group injected with 100 μl phosphate-buffered saline (PBS) in the same way. There were no significant effect of supplementation nor interaction with age on average body weights, T(3) and T(4) concentrations of non-injected chickens. After the primary immunization, α(1) -glycoprotein concentrations increased in all treatment groups except the CP group, and were significantly higher in the CH group in relation to the other groups. Fourteen and 18 days after the primary immunization, HSA injected chickens of both dietary treatments had significantly higher anti-HSA immunoglobulin G (IgG) levels than their PBS injected controls. No effect of stevioside supplementation was observed for IgG level. In conclusion, dietary stevioside inclusion can attenuate the pro-inflammatory response after stimulation of the innate immune response in broiler chickens.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Body Weight; Chickens; Diet; Dietary Supplements; Diterpenes, Kaurane; Enzyme-Linked Immunosorbent Assay; Glucosides; Humans; Immunoglobulin G; Male; Serum Albumin; Sweetening Agents; Thyroxine; Triiodothyronine

Several attempts to decrease sugar demand by introducing stevioside as a sugar substitute in children's food products have been made, but safety issues were concerned. This exploratory study investigated the effects of stevioside low dose (SL), high dose (SH) and low dose with inulin (SL + I) for 12 weeks on the body weight, organ relative weight, hematological and biochemical parameters and enzyme activities of young male rats. The SL dose used in this study was 15 mg kg(-1) per day and the SH dose was 100-fold the low dose. Enormous similarities in most parameters were observed with no significant differences between SL, SL + I and control except in the lipid profile. Total lipid reduction in SL and SL + I and significant high-density lipoprotein increase in SL + I were observed, which may be considered as clinically beneficial. Significant decreases in serum tartrate-resistant acid phosphatase activity were also observed in all treatments. Treatment with SH caused significant changes in all investigated toxicological parameters. The results indicated that, although the SL dose was higher than the stevioside temporary accepted daily intake (5.0 mg kg(-1) body weight), no toxicological effects were observed in SL or SL + I on body weight, organ relative weight, hematological and biochemical parameters or enzyme activities investigated in this study, whereas stevioside high dose (1500 mg kg(-1) per day) may be considered as a toxic dose for the same biological parameters in young male rats. However, the effects of SL, SH and SL + I on serum tartrate-resistant acid phosphatase activity need more investigation.

Topics: Acid Phosphatase; Animals; Biomarkers; Body Weight; Clinical Chemistry Tests; Diterpenes, Kaurane; Dose-Response Relationship, Drug; Glucosides; Hematologic Tests; Isoenzymes; Lipids; Male; Organ Size; Rats; Rats, Sprague-Dawley; Sweetening Agents; Tartrate-Resistant Acid Phosphatase; Toxicity Tests, Chronic

Stevioside is a non-caloric natural sweetener that does not induce a glycemic response, making it attractive as sweetener to diabetics and others on carbohydrate-controlled diets. Obesity is frequently associated with insulin resistance and increased inflammation and oxidative stress. Therefore, we investigated its effects on insulin resistance, inflammation and oxidative stress related to atherosclerosis in obese insulin-resistant mice.. Twelve-week-old mice were treated with stevioside (10 mg kg(-1), n=14) or placebo (n=20) for 12 weeks.. Stevioside had no effect on weight and triglycerides, but lowered glucose and insulin. Stevioside treatment improved adipose tissue maturation, and increased glucose transport, insulin signaling and antioxidant defense in white visceral adipose tissues. Together, these increases were associated with a twofold increase of adiponectin. In addition, stevioside reduced plaque volume in the aortic arch by decreasing the macrophage, lipid and oxidized low-density lipoprotein (ox-LDL) content of the plaque. The higher smooth muscle cell-to-macrophage ratio was indicative for a more stable plaque phenotype. The decrease in ox-LDL in the plaque was likely due to an increase in the antioxidant defense in the vascular wall, as evidenced by increased Sod1, Sod2 and Sod3. Circulating adiponectin was associated with improved insulin signaling and antioxidant defense in both the adipose tissue and the aorta of stevioside-treated mice.. Stevioside treatment was associated with improved insulin signaling and antioxidant defense in both the adipose tissue and the vascular wall, leading to inhibition of atherosclerotic plaque development and inducing plaque stabilization.

Topics: Adiponectin; Animals; Antioxidants; Atherosclerosis; Blood Glucose; Body Weight; Diterpenes, Kaurane; Glucosides; Insulin; Insulin Resistance; Mice; Mice, Obese; Obesity; Oxidative Stress; Signal Transduction; Sweetening Agents; Triglycerides

Stevioside, a glycoside present in the leaves of the plant, Stevia rebaudiana Bertoni (SrB), has acute insulinotropic effects in vitro. Its potential antihyperglycemic and blood pressure-lowering effects were examined in a long-term study in the type 2 diabetic Goto-Kakizaki (GK) rat. Rats were fed 0.025 g x kg(-1) x d(-1) of stevioside (purity > 99.6%) for 6 weeks. An intra-arterial catheter was inserted into the rats after 5 weeks, and conscious rats were subjected to arterial glucose tolerance test (2.0 g x kg(-1)) during week 6. Stevioside had an antihyperglycemic effect (incremental area under the glucose response curve [IAUC]): 985 +/- 20 (stevioside) versus 1,575 +/- 21 (control) mmol/L x 180 minutes, (P <.05), it enhanced the first-phase insulin response (IAUC: 343 +/- 33 [stevioside] v 136 +/- 24 [control] microU/mL insulin x 30 minutes, P <.05) and concomitantly suppressed the glucagon levels (total AUC: 2,026 +/- 234 [stevioside] v 3,535 +/- 282 [control] pg/mL x 180 minutes, P <.05). In addition, stevioside caused a pronounced suppression of both the systolic (135 +/- 2 v 153 +/- 5 mm Hg; P <.001) and the diastolic blood pressure (74 +/- 1 v 83 +/- 1 mm Hg; P <.001). Bolus injections of stevioside (0.025 g x kg(-1)) did not induce hypoglycemia. Stevioside augmented the insulin content in the beta-cell line, INS-1. Stevioside may increase the insulin secretion, in part, by induction of genes involved in glycolysis. It may also improve the nutrient-sensing mechanisms, increase cytosolic long-chain fatty acyl-coenzyme A (CoA), and downregulate phosphodiesterase 1 (PDE1) estimated by the microarray gene chip technology. In conclusion, stevioside enjoys a dual positive effect by acting as an antihyperglycemic and a blood pressure-lowering substance; effects that may have therapeutic potential in the treatment of type 2 diabetes and the metabolic syndrome.

Topics: Animals; Antihypertensive Agents; Blood Glucose; Blood Pressure; Body Weight; Cell Line; Diabetes Mellitus, Type 2; Diterpenes; Diterpenes, Kaurane; Fasting; Gene Expression Profiling; Glucagon; Glucose Tolerance Test; Glucosides; Hypoglycemic Agents; Insulin; Islets of Langerhans; Kinetics; Male; Rats; Rats, Wistar

The carcinogenic potential of stevioside, a compound that is used as a sweetener for food and drink, was examined in F344 rats of both sexes. Stevioside was added to powdered diet at concentrations of 0 (control), 2.5 and 5%. The doses were selected on the basis of results from a 13-wk subchronic toxicity study and administered to groups of 50 male and 50 female rats ad lib. for 104 wk. All surviving rats were killed at wk 108. Body weight gains were slightly depressed in line with the dose of stevioside, in both sexes, and a significant decrease in the final survival rate was observed for the 5% treated males. Histopathologically, however, there was no significantly altered development of neoplastic or non-neoplastic lesions attributable to the stevioside treatment in any organ or tissue, except for a decreased incidence of mammary adenomas in females and a reduced severity of chronic nephropathy in males. It is concluded that stevioside is not carcinogenic in F344 rats under the experimental conditions described.

Topics: Administration, Oral; Animals; Body Weight; Carcinogenicity Tests; Diterpenes; Diterpenes, Kaurane; Eating; Female; Glucosides; Kidney Diseases; Male; Neoplasms, Experimental; Organ Size; Rats; Rats, Inbred F344; Survival Rate; Sweetening Agents; Terpenes

Groups of 45 male and 45 female inbred Wistar rats were given diets containing stevioside (85% pure) at 0, 0.2, 0.6 or 1.2% for 2 yr. After 6, 12 and 24 months, five rats from each group were killed for haematological and clinical biochemical tests. Growth, food utilization and consumption, general appearance and mortality were similar in treated and control groups. The mean lifespan of rats given stevioside was not significantly different from that of the controls. No treatment-related changes were observed in haematological, urinary or clinical biochemical values at any stage of the study. The incidence and severity of non-neoplastic and neoplastic changes were unrelated to the level of stevioside in the diet. The maximum no-observed-effect level of stevioside was 1.2%, and an acceptable daily intake of stevioside for humans of 7.938 mg/kg body weight/day is suggested.

Topics: Animals; Body Weight; Carcinogens; Diterpenes; Diterpenes, Kaurane; Eating; Female; Glucosides; Lung; Male; Neoplasms, Experimental; Organ Size; Rats; Rats, Wistar; Sweetening Agents; Terpenes; Time Factors

A 13-week subchronic oral toxicity study of stevioside was carried out in F344 rats at dose levels of 0, 0.31, 0.62, 1.25, 2.5 and 5% in diet, to determine appropriate dose levels for a 2-year carcinogenicity study. The rats were randomly allocated to 6 groups, each consisting of 10 males and 10 females. No animals died during the administration period. Between the control and treated groups, there were no differences in body weight gain during the administration period and in food consumption in the later period of the study. LDH on biochemical investigation and single cell necrosis in the liver revealed by histopathological examination were increased in all male treated groups. These were not considered specific changes, because of the lack of any clear dose response, the relatively low severity and the limitation to males. Other parameters that were found to demonstrate significant differences on hematological and biochemical investigations were of minor toxicological significance. From these results, a concentration of 5% in diet was concluded to be a suitable maximum tolerable dose of stevioside for a 2-year carcinogenicity study in rats.

Topics: Administration, Oral; Animals; Body Weight; Diterpenes; Diterpenes, Kaurane; Female; Glucosides; Hematologic Tests; Male; Organ Size; Rats; Rats, Inbred F344; Terpenes; Time Factors