Steviol, the active principle of the Stevia sweetener, causes a reduction of the cells of the immunological system even consumed in low concentrations

Steviol is a natural diterpenoid glycoside isolated from Stevia rebaudiana Bertoni leaves and widely used as a non-caloric sweetener. In addition to their sweet taste, Steviol glycosides may also have some therapeutic benefits. There are few reports on the cytotoxicity of Steviol in human cells. Our objective was to test this sweetener under and at average concentrations of consumption, evaluating parameters of cytotoxicity, genotoxicity, and immunotoxicity. For this purpose, we made use of lymphocyte cultures and the analysis of their CD3⁺, CD4⁺, and CD8⁺ subpopulations. In a complementary way, the mechanism of action is proposed here by computational methods. Our results showed that Steviol reduces the number of lymphocytes due to falls of CD4⁺, CD8⁺, and CD4⁺CD8⁺ subpopulations. Besides, we observed an increase in the level of DNA damage and a gradual incidence of structural changes in the lymphocyte chromosomal sets. It was possible to propose that Steviol modulates gene expression, mainly interfering with the SESN1, NAP1L1, SOX4, and TREX1 genes. Although Steviol is used globally as a sweetener, its use should be cautious, as our study points out that Steviol has cytotoxic, genotoxic and mutagenic effects in the concentrations and conditions tested in the culture of human lymphocyte cells.

Keywords: In silico; In vitro; Stevia; Steviol; lymphocytes.