Protective effects of Stevia rebaudiana extracts on beta cells in lipotoxic conditions.

Marco Bugliani, Silvia Tavarini, Francesca Grano, Silvia Tondi, Serena Lacerenza, Laura Giusti, Maurizio Ronci, Anna Maidecchi, Piero Marchetti, Marta Tesi, Luciana G Angelini

Journal: Acta diabetologica 2022;59(1):113-126

PMID: 34499239

Abstract

AIMS

Stevia rebaudiana Bertoni leaf extracts have gained increasing attention for their potential protection against type 2 diabetes. In this study, we have evaluated the possible beneficial effects of Stevia rebaudiana leaf extracts on beta-cells exposed to lipotoxicity and explored some of the possible mechanisms involved.

METHODS

Extracts, deriving from six different chemotypes (ST1 to ST6), were characterized in terms of steviol glycosides, total phenols, flavonoids, and antioxidant activity. INS-1E beta cells and human pancreatic islets were incubated 24 h with 0.5 mM palmitate with or without varying concentrations of extracts. Beta-cell/islet cell features were analyzed by MTT assay, activated caspase 3/7 measurement, and/or nucleosome quantification. In addition, the proteome of INS-1E cells was assessed by bi-dimensional electrophoresis (2-DE).

RESULTS

The extracts differed in terms of antioxidant activity and stevioside content. As expected, 24 h exposure to palmitate resulted in a significant decrease of INS-1E cell metabolic activity, which was counteracted by all the Stevia extracts at 200 μg/ml. However, varying stevioside only concentrations were not able to protect palmitate-exposed cells. ST3 extract was also tested with human islets, showing an anti-apoptotic effect. Proteome analysis showed several changes in INS-1E beta-cells exposed to ST3, mainly at the endoplasmic reticulum and mitochondrial levels.

CONCLUSIONS

Stevia rebaudiana leaf extracts have beneficial effects on beta cells exposed to lipotoxicity; this effect does not seem to be mediated by stevioside alone (suggesting a major role of the leaf phytocomplex as a whole) and might be due to actions on the endoplasmic reticulum and the mitochondrion.

© 2021. The Author(s).

Address: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.; Department of Agriculture, Food and Environment, University of Pisa, Pisa, Italy.; Aboca SpA Società Agricola, Sansepolcro, Tuscany, Italy.; Department of Pharmacy, University of Pisa, Pisa, Italy.; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.; School of Pharmacy, University of Camerino, Camerino, Italy.; Department of Pharmacy and Centre for Advanced Studies and Technologies (CAST), University "G. D'Annunzio" of Chieti-Pescara, Chieti, Italy.; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. [email protected].; Department of Pharmacy and Centre for Advanced Studies and Technologies (CAST), University "G. D'Annunzio" of Chieti-Pescara, Chieti, Italy. [email protected].; Department of Agriculture, Food and Environment, University of Pisa, Pisa, Italy.; Centro Interdipartimentale NUTRAFOOD, University of Pisa, Pisa, Italy.
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