title: Loading into nanoparticles improves quercetin's efficacy in preventing neuroinflammation induced by oxysterols.
abstract: Chronic inflammatory events appear to play a fundamental role in Alzheimer's disease (AD)-related neuropathological changes, and to result in neuronal dysfunction and death. The inflammatory responses observed in the AD brain include activation and proliferation of glial cells, together with up-regulation of inflammatory mediators and of free radicals. Along with glial cells, neurons themselves can also react and contribute to neuroinflammatory changes in the AD brain, by serving as sources of inflammatory mediators. Because excess cholesterol cannot be degraded in the brain, it must be excreted from that organ as cholesterol oxidation products (oxysterols), in order to prevent its accumulation. Among risk factors for this neurodegenerative disease, a mechanistic link between altered cholesterol metabolism and AD has been suggested; oxysterols appear to be the missing linkers between the two, because of their neurotoxic effects. This study shows that 24-hydroxycholesterol, 27-hydroxycholesterol, and 7β-hydroxycholesterol, the three oxysterols potentially implicated in AD pathogenesis, induce some pro-inflammatory mediator expression in human neuroblastoma SH-SY5Y cells, via Toll-like receptor-4/cyclooxygenase-2/membrane bound prostaglandin E synthase (TLR4/COX-2/mPGES-1); this clearly indicates that oxysterols may promote neuroinflammatory changes in AD. To confirm this evidence, cells were incubated with the anti-inflammatory flavonoid quercetin; remarkably, its anti-inflammatory effects in SH-SY5Y cells were enhanced when it was loaded into β-cyclodextrin-dodecylcarbonate nanoparticles, versus cells pretreated with free quercetin. The goal of loading quercetin into nanoparticles was to improve its permeation across the blood-brain barrier into the brain, and its bioavailability to reach target cells. The findings show that this drug delivery system might be a new therapeutic strategy for preventing or reducing AD progression.
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Testa
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Gamba
authors.affiliation: Department of Pharmaceutical Technology, University of Ankara, Ankara, Turkey.
authors.forename: Ulya
authors.initials: U
authors.lastname: Badilli
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Gargiulo
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Maina
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy.
authors.forename: Tina
authors.initials: T
authors.lastname: Guina
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Calfapietra
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Biasi
authors.affiliation: Department of Drug Science and Technology, University of Torino, Torino, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cavalli
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Poli
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Leonarduzzi
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000975:Antioxidants; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D006888:Hydroxycholesterols; D018836:Inflammation Mediators; D019012:Integrin beta1; D016209:Interleukin-8; D047392:beta-Cyclodextrins; C044563:24-hydroxycholesterol; C011724:cholest-5-en-3 beta,7 alpha-diol; C076996:27-hydroxycholesterol; D011794:Quercetin; D020780:Matrix Metalloproteinase 9; C031215:betadex