Abstract
Microalgae are increasingly recognized as valuable dietary supplements due to their rich nutritional composition and the presence of bioactive metabolites with antioxidant, antitumor, and metabolism-modulating activities. This study evaluated the nutraceutical potential of a methanolic extract of Scenedesmus sp. using an integrated in vitro, in vivo, and metabolomic approach. The extract exhibited selective cytotoxicity against L5178Y-R murine lymphoma cells while showing low toxicity toward human peripheral blood mononuclear cells, indicating a favorable safety and selectivity profile. Additionally, it demonstrated moderate antioxidant activity, a significant antihemolytic effect, and no hemolytic activity even at high concentrations, supporting its hematological safety. In vivo assays showed that oral administration of doses up to 1000 mg/kg was well tolerated, with no adverse effects on body weight or hepatic biochemical markers. Treated animals displayed improved systemic antioxidant responses and enhanced glucose tolerance. Metabolomic analysis revealed a profile enriched in essential amino acids, osmolytes, organic acids, and bioactive metabolites such as β-hydroxybutyrate and betaine, compounds associated with metabolic regulation, redox balance, and epigenetic modulation. Overall, these findings highlight Scenedesmus sp. as a promising nutraceutical source with potential application as a complementary strategy for cancer prevention or treatment.