Glycosides from Stevia rebaudiana Bertoni Possess Insulin-Mimetic and Antioxidant Activities in Rat Cardiac Fibroblasts.

Cecilia Prata,Cristina Angeloni,Benedetta Rizzo,Tullia Maraldi,Francesco Vieceli Dalla Sega,Silvana Hrelia,Laura Zambonin,Diana Fiorentini

doi:10.1155/2017/3724545

Abstract

Stevia rebaudiana Bertoni is a shrub having a high content of sweet diterpenoid glycosides in its leaves, mainly stevioside and rebaudioside A, which are used as noncaloric, natural sweeteners. The aim of this study was to deepen the knowledge about the insulin-mimetic effect exerted by four different mixtures of steviol glycosides, rich in stevioside and rebaudioside A, in neonatal rat cardiac fibroblasts. The potential antioxidant activity of these steviol glycosides was also assessed, as oxidative stress is associated with diabetes. Likewise the insulin effect, steviol glycosides caused an increase in glucose uptake into rat fibroblasts by activating the PI3K/Akt pathway, thus inducing Glut4 translocation to the plasma membrane. The presence of S961, an insulin antagonist, completely abolished these effects, allowing to hypothesize that steviol glycosides could act as ligands of the same receptor engaged by insulin. Moreover, steviol glycosides counteracted oxidative stress by increasing reduced glutathione intracellular levels and upregulating expression and activity of the two antioxidant enzymes superoxide dismutase and catalase. The present work unravels the insulin-mimetic effect and the antioxidant property exerted by steviol glycosides, suggesting their potential beneficial role in the cotreatment of diabetes and in health maintenance.

Highlights

Stevia rebaudiana Bertoni is a shrub belonging to the Asteraceae family, native to Paraguay and Brazil, and has been cultivated in many parts of the world [1,2,3]
Rat cardiac fibroblasts were treated with increasing concentrations of REB A 97 (R97), R60, SG, or TRU (0.5–5 mg/mL) for 24 hours to investigate their direct effect on cell integrity/damage
Neonatal rat cardiac fibroblasts were incubated for 1 hour with R97, R60, SG, or TRU (1 mg/mL) or with 100 nM insulin and assayed for glucose transport activity

Summary

Introduction

Stevia rebaudiana Bertoni is a shrub belonging to the Asteraceae family, native to Paraguay and Brazil, and has been cultivated in many parts of the world [1,2,3]. Several studies suggest that Stevia has antihyperglycaemic, antihypertensive, antitumour, antidiarrheal, diuretic, anti-inflammatory, and immune-modulatory effects [12]. Owing to these characteristics, leaf extracts rich in steviol glycosides, such as stevioside and rebaudioside A, have been authorized as commercial sweeteners and food additives [13], as the safety of high-purity steviol glycosides has been extensively reviewed in the published literature and by national and international food safety agencies [14].

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