Enantioselective Modulatory Effects of Naringenin Enantiomers on the Expression Levels of miR‐17‐3p Involved in Endogenous Antioxidant Defenses

Naringenin is a flavanone present in citrus fruit as a mixture of chiral isomers. The numerous biological properties attributed to this compound include antioxidant and anti‐inflammatory activities, even though the molecular mechanisms of these remain unknown. This study aims to evaluate the effects of racemic and enantiomeric naringenin on the expression levels of miR‐17‐3p, miR‐25‐5p and relative mRNA targets, to elucidate the mechanisms underlying these antioxidant and anti‐inflammatory properties. Caco‐2 cells, a well characterized in vitro model which mimics the intestinal barrier, were treated with subtoxic concentrations of racemate and enantiomers. The expression levels of miR‐17‐3p and miR‐25‐5p were determined by Real‐Time PCR and were found to be decreased for both miRNAs. miR‐17‐3p behavior was in agreement with the increased levels of target mRNAs coding for two antioxidant enzymes, manganese‐dependent superoxide dismutase (MnSOD) and glutathione peroxidase 2 (GPx2), while expression levels of miR‐25‐5p were not in agreement with its target mRNAs, coding for two pro‐inflammatory cytokines, Tumor necrosis factor‐alpha (TNF‐α) and Interleukin‐6 (IL‐6). These results lead to the conclusion that naringenin could exert its antioxidant activity through epigenetic regulation operated by miRNAs, while anti‐inflammatory activity is regulated by other miRNAs and/or mechanisms.