rebaudioside-a and Neoplasms

Stevia rebaudiana Bertoni is a sweet and nutrient-rich plant belonging to the Asteraceae family. Stevia leaves contain steviol glycosides including stevioside, rebaudioside (A to F), steviolbioside, and isosteviol, which are responsible for the plant's sweet taste, and have commercial value all over the world as a sugar substitute in foods, beverages and medicines. Among the various steviol glycosides, stevioside, rebaudioside A and rebaudioside C are the major metabolites and these compounds are on average 250-300 times sweeter than sucrose. Steviol is the final product of Stevia metabolism. The metabolized components essentially leave the body and there is no accumulation. Beyond their value as sweeteners, Stevia and its glycosdies possess therapeutic effects against several diseases such as cancer, diabetes mellitus, hypertension, inflammation, cystic fibrosis, obesity and tooth decay. Studies have shown that steviol glycosides found in Stevia are not teratogenic, mutagenic or carcinogenic and cause no acute and subacute toxicity. The present review provides a summary on the biological and pharmacological properties of steviol glycosides that might be relevant for the treatment of human diseases.

Topics: Cystic Fibrosis; Dental Caries; Diabetes Mellitus; Diterpenes, Kaurane; Glycosides; Humans; Hypertension; Inflammation; Neoplasms; Obesity; Plant Extracts; Stevia

Natural preservatives are causing a rethinking of current preservation means. As a sweetener resource, exploitation of Stevia rebaudiana leaves (SRLs) is still restricted due to human conventional cognition. Herein, Lactobacillus plantarum fermented SRLs containing diverse free secondary metabolites derived from microbial deglycosylation and bioenzymatic decomposition were investigated. The apparent resistance to typical foodborne bacteria (Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomoas aeruginosa, Bacillus amyloliquefaciens) by fermented SRLs and their extracts were validated. The metabolite diversity and in-depth organic solvent extraction gave the possibilities for better antimicrobial actions, anti-HepG2/SGC-7901 cells in vitro in contrast with aqueous extract of unfermented SRLs. Crucially, compound identification and attribution revealed that fermentation products may be maximally contributing to antimicrobial and antitumor mechanisms rather than intrinsic plant and/or microbial components. Additionally, pork sausage models with 15 g/kg ethyl acetate extract as a preservative candidate presented preferred storage characteristics (21 days and 37 °C) compared to those without ethyl acetate extract, e.g. the minimal total plate count (3.86 ± 0.27 log CFU/g), peroxsignide value (8.02 ± 0.92 meq/kg), and acid value (2.01 ± 0.04 (KOH)/(mg/g)).

Topics: Cell Line; Escherichia coli; Humans; Lactobacillus plantarum; Neoplasms; Preservatives, Pharmaceutical; Stevia

The use of steviol glycosides as non-caloric sweeteners has proven to be beneficial for patients with type 2 diabetes mellitus (T2D), obesity, and metabolic syndrome. However, recent data demonstrate that steviol and stevioside might act as glucocorticoid receptor (GR) agonists and thus correlate with adverse effects on metabolism. Herein, we evaluated the impact of steviol, steviol glycosides, and a Greek-derived stevia extract on a number of key steps of GR signaling cascade in peripheral blood mononuclear cells (PBMCs) and in Jurkat leukemia cells. Our results revealed that none of the tested compounds altered the expression of primary GR-target genes (GILZ, FKPB5), GR protein levels or GR subcellular localization in PBMCs; those compounds increased GILZ and FKPB5 mRNA levels as well as GRE-mediated luciferase activity, inducing in parallel GR nuclear translocation in Jurkat cells. The GR-modulatory activity demonstrated by stevia-compounds in Jurkat cells but not in PBMCs may be due to a cell-type specific effect.

Topics: Adrenocorticotropic Hormone; Cell Nucleus; Cell Survival; Dexamethasone; Diterpenes, Kaurane; Gene Expression Regulation; Glucosides; Humans; Hydrocortisone; Jurkat Cells; Leukocytes, Mononuclear; Luciferases; Neoplasms; Plant Extracts; Receptors, Glucocorticoid; Response Elements; RNA, Messenger; Signal Transduction; Stevia; Tacrolimus Binding Proteins; Transcription Factors

Steviol glycosides are currently being used as natural sweeteners by the food industry and Stevia rebaudiana has long been used as a sweet plant in South America for patients suffering from diabetes. In this study, a Stevia rebaudiana ethanolic extract (SREE) was prepared, analysed and tested for antioxidant activity in terms of free radical scavenging properties and antiproliferative effects in cervix (HeLa), pancreatic (MiaPaCa-2) and colonic (HCT116) cancer cells. The antiproliferative mechanism was confirmed by testing the effects on cyclin D1-CDK4. Bioassays were also performed for the diterpene glycoside stevioside. Our results demonstrate that the extract acts as an antioxidant being able to scavenge free radicals, but this activity was not due to stevioside. The extract also induced cell death in the three cell lines, being more active against cervix cancer cells (HeLa); however, the concentration of stevioside needed to produce antiproliferative effects was higher than the amount of steviol glycosides found in a lower dose of extract inducing cell death. In addition, the extract clearly inhibited CDK4 whereas stevioside did not, concluding that the antiproliferative activity of stevia may be due to inhibition of cyclin-dependent kinases performed by other compounds of the extract.

Topics: Antioxidants; Cell Line, Tumor; Cell Proliferation; Diterpenes, Kaurane; Glucosides; Humans; Neoplasms; Plant Extracts; Plant Leaves; Stevia

Seventeen steviol derivatives, i.e., 2-18, and 19 isosteviol derivatives, i.e., 19-37, were prepared from a diterpenoid glycoside, stevioside (1). Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines, nine steviol derivatives, i.e., 5-9 and 11-14, and five isosteviol derivatives, i.e., 28-32, exhibited activities with single-digit micromolar IC(50) values against one or more cell lines. All of these active compounds possess C(19)-O-acyl group, and among which, ent-kaur-16-ene-13,19-diol 19-O-4',4',4'-trifluorocrotonate (14) exhibited potent cytotoxicities against four cell lines with IC(50) values in the range of 1.2-4.1 μM. Compound 14 induced typical apoptotic cell death in HL60 cells upon evaluation of the apoptosis-inducing activity by flow-cytometric analysis. These results suggested that acylation of the 19-OH group of kaurane- and beyerane-type diterpenoids might be useful for enhancement of their cytotoxicities with apoptosis-inducing activity.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cell Survival; Diterpenes, Kaurane; Humans; Neoplasms; Stevia