title: Structure-dependent inhibition of gelatinases by dietary antioxidants in rat astrocytes and sera of multiple sclerosis patients.
abstract: We investigated whether polyphenols modulate the expression and activity of the enzymes gelatinases A (MMP-2) and B (MMP-9), involved in the pathogenesis of multiple sclerosis (MS). LPS-activated primary rat astrocytes were treated with the flavonoids quercetin (QRC) and cathechins [green tea extract (GTE)] and the non-flavonoids resveratrol (RSV) and tyrosol/hydroxytyrosol (Oliplus). As assessed by zymography and RT-PCR, RSV and Oliplus, but not QRC and GTE, dose-dependently inhibited the LPS-induced levels and mRNA expression of MMP-2 and MMP-9. By contrast, in cell-free systems direct inhibition of gelatinase activity in MS sera was determined by QRC and GTE, but not by RSV. Oliplus was only partially effective. Our results indicate that the flavonoids and non-flavonoids tested exert their inhibitory effect on MMPs, displaying different mechanisms of action, possibly related to their structure. Therefore, their combined use may represent a powerful tool for the down-regulation of MMPs in the course of MS.
authors.affiliation: Department of Biochemistry and Molecular Biology, Ernesto Quagliariello, University of Bari, Via Orabona 4, 70126, Bari, Italy. m.g.liuzzi@biologia.uniba.it
authors.forename: Grazia Maria
authors.initials: GM
authors.lastname: Liuzzi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Latronico
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Branà
authors.forename: Pasqua
authors.initials: P
authors.lastname: Gramegna
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Coniglio
authors.forename: Rocco
authors.initials: R
authors.lastname: Rossano
authors.forename: Marilena
authors.initials: M
authors.lastname: Larocca
authors.forename: Paolo
authors.initials: P
authors.lastname: Riccio
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D002478:Cells, Cultured; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D015394:Molecular Structure; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D059808:Polyphenols; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D010636:Phenols; D059808:Polyphenols; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9