| Summary: | <i>Spirulina</i> is rich in various antioxidants and nutraceuticals and it has proven to be effective in the treatment of various pathological conditions. This study explores the antioxidant effect of fermented and non-fermented <i>Spirulina</i> extracts on the proteome level using the yeast <i>Saccharomyces cerevisiae</i> as a model organism. Yeast cells were treated with fermented <i>Spirulina</i> water extract (SV), non-fermented <i>Spirulina</i> water extract (NFV), fermented <i>Spirulina</i> ethanol extract (SE), and non-fermented <i>Spirulina</i> ethanol extract (NFE). Cell lysates were prepared, and label-free quantitative proteome analysis was performed. In SV, when compared to NFV samples, the levels of most differentially expressed proteins were upregulated. Alternatively, SE compared to NFE samples showed a significant downregulation for the majority of the analyzed proteins involved in different cellular processes. Additionally, a higher downregulation of stress response related proteins was observed in SE compared to NFE samples, while their abundance in SV samples increased compared to NFV. This study provided a global view, on a proteome level, of how cells cope with exogenous antioxidants and remodel their cellular processes to maintain metabolic and redox balance. Furthermore, it combined for the first time the analysis of different extract effect, including the contribution of lactic acid fermentation to the cell activity.
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