title: Modulation of BV-2 microglia functions by novel quercetin pivaloyl ester.
abstract: Chronic inflammation in brain plays a critical role in major neurodegenerative diseases such as Alzheimer's, Parkinson's disease, stroke or multiple sclerosis. Microglia, resident macrophages and intristinc components of CNS, appear to be main effectors in this pathological process. Quercetin, a naturally occurring flavonoid, was proven to downregulate inflammatory genes in microglia. Synthetically modified quercetin, 3'-O-(3-chloropivaloyl) quercetin (CPQ), is assumed to possess better biological availability and enhanced antioxidant properties. In the present study, antineuroinflammatory capability of the novel compound CPQ was assessed in BV-2 microglial cells. Our data show that treatment with CPQ attenuated the production of the inflammatory mediators, nitric oxide (NO) and tumour necrosis factor-α (TNF-α), in LPS-stimulated microglia somewhat more efficiently than did quercetin (p > 0.05 for CPQ vs. quercetin-treated group). Also, protein level of inducible NO synthase (iNOS) in LPS-activated BV-2 microglia was to some extent more effectively supressed by CPQ than by unmodified flavonoid. In consistence with the extent of their effects on pro-inflammatory markers, CPQ and quercetin showed down-regulation of NFκB activation. This quercetin analogue caused also a decline in BV-2 microglia proliferation with interfering with cell cycle progression (p < 0.001 for CPQ vs. quercetin-treated group). However, CPQ did not remarkably affect cell viability. In addition, CPQ showed a minor better suppression of PMA-induced generation of superoxide than did quercetin. Neither CPQ nor quercetin influenced phagocytosis of BV-2 cells. These results point to the therapeutic potential of 3'-O-(3-chloropivaloyl)quercetin (CPQ) as a novel antiinflammatory drug in neurodegenerative diseases, mediating favourable modulation of pro-inflammatory functions of microglia.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dubravska cesta 9, 841 04 Bratislava, Slovak Republic.
authors.forename: Nataša
authors.initials: N
authors.lastname: Mrvová
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dubravska cesta 9, 841 04 Bratislava, Slovak Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Škandík
authors.affiliation: Faculty of Medicine Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovak Republic.
authors.forename: Marcela
authors.initials: M
authors.lastname: Kuniaková
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dubravska cesta 9, 841 04 Bratislava, Slovak Republic. Electronic address: rackova.luci@gmail.com.
authors.forename: Lucia
authors.initials: L
authors.lastname: Račková
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009103:Multiple Sclerosis / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D011794:Quercetin
keywords: 3′-O-(3-chloropivaloyl)quercetin; Anti-neuroinflammatory efficacy; BV-2 microglia; Quercetin