PMID- 28264488 OWN - NLM STAT- MEDLINE DCOM- 20170817 LR - 20181113 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 9 IP - 3 DP - 2017 Feb 28 TI - Enantioselective Modulatory Effects of Naringenin Enantiomers on the Expression Levels of miR-17-3p Involved in Endogenous Antioxidant Defenses. LID - 10.3390/nu9030215 [doi] LID - 215 AB - 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-alpha) 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. FAU - Curti, Valeria AU - Curti V AD - Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, Pavia University, Viale Taramelli 12, 27100 Pavia, Italy. valeriacurti@kolinpharma.com. AD - KOLINPHARMA S.p.A., Lainate, Corso Europa 5, 20020 Lainate, Italy. valeriacurti@kolinpharma.com. FAU - Di Lorenzo, Arianna AU - Di Lorenzo A AD - Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, Pavia University, Viale Taramelli 12, 27100 Pavia, Italy. arianna.dilorenzo01@universitadipavia.it. AD - KOLINPHARMA S.p.A., Lainate, Corso Europa 5, 20020 Lainate, Italy. arianna.dilorenzo01@universitadipavia.it. FAU - Rossi, Daniela AU - Rossi D AD - Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, Pavia University, Viale Taramelli 12, 27100 Pavia, Italy. daniela.rossi@unipv.it. FAU - Martino, Emanuela AU - Martino E AD - Department of Earth and Environmental Sciences, University of Pavia, Via S. Epifanio 14, 27100 Pavia, Italy. emanuela.martino@unipv.it. FAU - Capelli, Enrica AU - Capelli E AD - Department of Earth and Environmental Sciences, University of Pavia, Via S. Epifanio 14, 27100 Pavia, Italy. enrica.capelli@unipv.it. FAU - Collina, Simona AU - Collina S AD - Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, Pavia University, Viale Taramelli 12, 27100 Pavia, Italy. simona.collina@unipv.it. FAU - Daglia, Maria AU - Daglia M AD - Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, Pavia University, Viale Taramelli 12, 27100 Pavia, Italy. maria.daglia@unipv.it. LA - eng PT - Journal Article DEP - 20170228 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Antioxidants) RN - 0 (Flavanones) RN - 0 (Interleukin-6) RN - 0 (MIRN17 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.11.1.- (GPX2 protein, human) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - HN5425SBF2 (naringenin) SB - IM MH - Antioxidants/*metabolism MH - Caco-2 Cells MH - Down-Regulation MH - Epigenesis, Genetic MH - Flavanones/*pharmacology MH - Glutathione Peroxidase/genetics/metabolism MH - Humans MH - Interleukin-6/genetics/metabolism MH - MicroRNAs/genetics/*metabolism MH - RNA, Messenger/genetics/metabolism MH - Superoxide Dismutase/genetics/metabolism MH - Tumor Necrosis Factor-alpha/genetics/metabolism MH - Up-Regulation PMC - PMC5372878 OTO - NOTNLM OT - naringenin racemate OT - antioxidant enzymes OT - caco-2 cells OT - epigenetics OT - microRNA OT - naringenin enantiomers OT - pro-inflammatory cytokines COIS- The authors have declared no conflict of interest. EDAT- 2017/03/08 06:00 MHDA- 2017/08/18 06:00 PMCR- 2017/03/01 CRDT- 2017/03/08 06:00 PHST- 2016/11/28 00:00 [received] PHST- 2017/02/24 00:00 [accepted] PHST- 2017/03/08 06:00 [entrez] PHST- 2017/03/08 06:00 [pubmed] PHST- 2017/08/18 06:00 [medline] PHST- 2017/03/01 00:00 [pmc-release] AID - nu9030215 [pii] AID - nutrients-09-00215 [pii] AID - 10.3390/nu9030215 [doi] PST - epublish SO - Nutrients. 2017 Feb 28;9(3):215. doi: 10.3390/nu9030215.