title: Enantioselective Modulatory Effects of Naringenin  Enantiomers on the Expression Levels of miR-17-3p  Involved in Endogenous Antioxidant Defenses.
abstract: 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.
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, Pavia University, Viale Taramelli 12, 27100 Pavia, Italy. valeriacurti@kolinpharma.com.|KOLINPHARMA S.p.A., Lainate, Corso Europa 5, 20020 Lainate, Italy. valeriacurti@kolinpharma.com.
authors.forename: Valeria
authors.initials: V
authors.lastname: Curti
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, Pavia University, Viale Taramelli 12, 27100 Pavia, Italy. arianna.dilorenzo01@universitadipavia.it.|KOLINPHARMA S.p.A., Lainate, Corso Europa 5, 20020 Lainate, Italy. arianna.dilorenzo01@universitadipavia.it.
authors.forename: Arianna
authors.initials: A
authors.lastname: Di Lorenzo
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, Pavia University, Viale Taramelli 12, 27100 Pavia, Italy. daniela.rossi@unipv.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rossi
authors.affiliation: Department of Earth and Environmental Sciences, University of Pavia, Via S. Epifanio 14, 27100 Pavia, Italy. emanuela.martino@unipv.it.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Martino
authors.affiliation: Department of Earth and Environmental Sciences, University of Pavia, Via S. Epifanio 14, 27100 Pavia, Italy. enrica.capelli@unipv.it.
authors.forename: Enrica
authors.initials: E
authors.lastname: Capelli
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, Pavia University, Viale Taramelli 12, 27100 Pavia, Italy. simona.collina@unipv.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Collina
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, Pavia University, Viale Taramelli 12, 27100 Pavia, Italy. maria.daglia@unipv.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Daglia
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D018938:Caco-2 Cells; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D044950:Flavanones / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D044950:Flavanones; D015850:Interleukin-6; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C117436:GPX2 protein, human; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C005273:naringenin
keywords: naringenin racemate;  antioxidant enzymes;  caco‐2 cells;  epigenetics;  microRNA;  naringenin enantiomers;  pro‐inflammatory  cytokines