Stevioside

Int Immunopharmacol. 2014 Sep;22(1):192-9.

Stevioside inhibits inflammation and apoptosis by regulating TLR2 and TLR2-related proteins in S. aureus-infected mouse mammary epithelial cells.[Pubmed: 24975657]

METHODS AND RESULTS:
The object of this study was to investigate the anti-inflammatory and anti-apoptosis function of Stevioside and the possible molecular mechanisms for such activity in Staphylococcus aureus (S. aureus)-infected mouse mammary epithelial cells (MMECs). The cells were treated with varying doses of Stevioside before infection with S. aureus. The live/dead cells were detected by immunofluorescence microscopy. The pro-inflammatory cytokines were determined by ELISA. The mRNA of TLR2 and proteins related to NF-κB, MAPK and apoptosis were analyzed by q-PCR. The relative protein expression levels were determined by Western blot. The results indicated that Stevioside inhibited the mRNA and protein expression of TNF-α, IL-6 and IL-1β dose-dependently in S. aureus-stimulated MMECs. Stevioside suppressed the S. aureus-induced expression of TLR2 and proteins of the NF-κB and MAPK pathways as well as apoptosis. The mRNA levels of IκBα, p38, ERK, JNK, p65, caspase-3 and Bax were not influenced by the Stevioside treatment.
CONCLUSIONS:
Stevioside exerts anti-inflammatory and anti-apoptotic properties by inhibiting the release of cytokines and the activation of TLR2 and proteins of the NF-κB and MAPK signaling pathways, as well as caspase-3 and Bax.

Saudi J Biol Sci . 2019 Nov;26(7):1596-1601.

Stevioside mediated chemosensitization studies and cytotoxicity assay on breast cancer cell lines MDA-MB-231 and SKBR3[Pubmed: 31762632]

Abstract Cancer is one of the most impacting life-threatening disease for the human populace. Hence, over the years we have seen a consistent interest to study and investigate new treatments to cure and prevent this disease. Medicinal plants have played a progressive part in treatment since many years. In this research study, we have explored the cytotoxicity effect of purified bioactive compound isolated from Stevia rebaudiana leaves and the key mechanism responsible for apoptosis in human breast cancer cells. The anticancer properties of Stevia rebaudiana leaves has been suggested in earlier literature. Hence, the aim of this study was to investigate the cytotoxicity of purified Stevioside in human breast cancer cell lines MDA-MB-231 and SKBR3. Results showed that purified Stevioside inhibited the growth of cancerous cell lines. The IC50 obtained after treatment with Stevioside on cancer cells MDA-MB-231 and SKBR3 are 55 μM and 66 μM respectively. This shows purified Stevioside is capable of inducing apoptosis indicating its promising anticancer activity. However, so far chemosensitization effects of Stevioside on breast cancer have not been fully explained by other studies. Hence, additionally, this study also evaluates the chemosensitization potential of Stevioside in combination with 5-FU. This research study shows the importance of Stevia rebaudiana as a good source of bioactive compounds with high anti-cancer property. Keywords: Apoptosis; Cancer; Cytotoxicity effects; MDA-MB-231; SKBR3; Stevia rebaudiana.

Braz Oral Res. 2014 Jan-Feb;28(1).

Effects of lactose-containing stevioside sweeteners on dental biofilm acidogenicity.[Pubmed: 25098824]

The aim of this study was to evaluate the effect of a commercial lactose-containing Stevioside sweetener on biofilm acidogenicity in vivo.
METHODS AND RESULTS:
Nine volunteers refrained from brushing their teeth for 3 days in five phases. On the 4th day of each phase, the pH of the biofilm was measured by the "Strip method". Interproximal plaque pH was measured before and up to 60 minutes after a 10 mL mouthrinse for 1 minute with the test solutions: I - sweetener with 93% lactose and 7% Stevioside; II - sweetener with 6.8% saccharin, 13.6% cyclamate, and 0.82% Stevioside; III - 18% sucrose solution (positive control); IV - mineral water (negative control); and V- 93% lactose solution. The results revealed that the most pronounced pH fall was found with sucrose (positive control), followed by the 93% lactose solution, the sweetener with lactose + Stevioside, the sweetener with saccharin + cyclamate + Stevioside, and finally water (negative control). According to the area under the curve, the two sweeteners containing Stevioside were significantly different, and the sweetener with lactose + Stevioside was significantly different from water but not from sucrose. The critical pH for dentin demineralization (pH ≤ 6.5) was reached by all volunteers after rinsing with sucrose solution, lactose solution, and the Stevioside + lactose sweetener.
CONCLUSIONS:
Analysis of the data suggests that lactose-containing Stevioside sweeteners may be cariogenic, especially to dentin.

Metabolism. 2003 Mar;52(3):372-8.

Antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat.[Pubmed: 12647278 ]

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.
METHODS AND RESULTS:
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.
CONCLUSIONS:
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.

J Sci Food Agric. 2013 Dec;93(15):3820-5.

Anti-inflammatory and immunomodulatory activities of stevioside and steviol on colonic epithelial cells.[Pubmed: 23794454]

Stevioside is a natural non-caloric sweetener isolated from Stevia rebaudiana Bertoni leaves. We have proposed its effect on attenuation of tumour necrosis factor α (TNF-α) and interleukin 1β (IL-1β) release in lipopolysaccharide (LPS)-stimulated monocytes.
METHODS AND RESULTS:
In this study, the anti-inflammatory and immunomodulatory activities of Stevioside and its metabolite, steviol, on human colon carcinoma cell line (Caco-2) were evaluated. Stevioside and steviol, in the doses used in this study, had no cytotoxicity on Caco-2 cells. Anti-inflammatory activities of these two compounds were observed by potentially suppressed LPS-mediated TNF-α, IL-1β and IL-6 release. In addition, Stevioside and steviol showed immunomodulatory effects on IκBα activation and nuclear factor kappa B (NF-κB) suppression in western blotting.
CONCLUSIONS:
Stevioside and steviol attenuate LPS-induced pro-inflammatory cytokine productions by affecting cytokine gene expression via IκBα/NF-κB signalling pathway.

Vojnosanit Pregl. 2014 Jul;71(7):667-72.

Effect of aqueous solution of stevioside on pharmacological properties of some cardioactive drugs.[Pubmed: 25109114]

Animal Models: Rats
Formulation: 200 mg/mL in the physiological saline
Dosages: 200 mg/kg/day for 5 days
Administration: i.p.