Antioxidant Activity of Leaf Extracts from Stevia rebaudiana Bertoni Exerts Attenuating Effect on Diseased Experimental Rats: A Systematic Review and Meta-Analysis

Stevia (Stevia rebaudiana Bertoni) is an aromatic plant known for its high sweetening power ascribed to its glycosides. Stevia also contains several bioactive compounds showing antioxidant, antiproliferative, antimicrobial, and anti-inflammatory activities. Since inflammation and oxidative stress play critical roles in the pathogenesis of many diseases, stevia emerges as a promising natural product that could support human health. In this study we set out to investigate the way stevia affects oxidative stress markers (e.g., SOD, CAT, GPx, GSH, MDA) in diseased rats administered stevia leaf extracts or glycosides. To this end, we performed an inclusive literature search, following PRISMA guidelines, and recruited multivariate meta-analysis and meta-regression to synthesize all available data on experimental animal models encountering (a) healthy, (b) diseased, and (c) stevia-treated diseased rats. From the 184 articles initially retrieved, 24 satisfied the eligibility criteria, containing 104 studies. Our results demonstrate that regardless of the assay employed, stevia leaf extracts restored all oxidative stress markers to a higher extent compared to pure glycosides. Meta-regression analysis revealed that results from SOD, CAT, GSH, and TAC assays are not statistically significantly different (p = 0.184) and can be combined in meta-analysis. Organic extracts from stevia leaves showed more robust antioxidant properties compared to aqueous or hydroalcoholic ones. The restoration of oxidative markers ranged from 65% to 85% and was exhibited in all tested tissues. Rats with diabetes mellitus were found to have the highest restorative response to stevia leaf extract administration. Our results suggest that stevia leaf extract can act protectively against various diseases through its antioxidant properties. However, which of each of the multitude of stevia compounds contribute to this effect, and to what extent, awaits further investigation.