title: The Plant-Derived Chalcone 2,2',5'-Trihydroxychalcone Provides Neuroprotection against Toll-Like Receptor 4 Triggered Inflammation in Microglia.
abstract: Chalcones are plant metabolites with potential for therapeutic exploitation as antioxidant, anti-inflammatory, and antiproliferative agents. Here we explored the neuroprotective effects of 2,2',5'-trihydroxychalcone (225THC), a potent antioxidant with radical-scavenging properties. 225THC was found to be a potent inhibitor of apoptosis in stimulated primary rat neuronal cultures. This was likely mediated by an anti-inflammatory effect on microglial cells since 225THC inhibited LPS-stimulated TNF-α and IL-6 secretion from primary rat microglia and modulated the cytokine/chemokine profile of BV2 microglial cells. Additionally, 225THC inhibited LPS-evoked inducible nitric oxide synthase expression but did not influence endogenous superoxide generation. Microglial flow cytometric analyses indicated the 225THC treatment induced a shift from an M1-like phenotype to a more downregulated microglial profile. Taken together these data suggest that the chalcone 2,2',5'-trihydroxychalcone can modulate neuroinflammatory activation in brain-derived microglia and holds promise as a therapeutic in neuroinflammatory conditions.
authors.affiliation: Mayne Medical School, 288 Herston Road, Brisbane, QLD 4006, Australia.
authors.forename: Manasi
authors.initials: M
authors.lastname: Jiwrajka
authors.affiliation: Department of Neuroinflammation, University College London Institute of Neurology, 1 Wakefield Street, London WC1N 1PK, UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Phillips
authors.affiliation: Department of Neuroinflammation, University College London Institute of Neurology, 1 Wakefield Street, London WC1N 1PK, UK.
authors.forename: Matt
authors.initials: M
authors.lastname: Butler
authors.affiliation: Department of Chemistry, Vassar College, 124 Raymond Avenue, Poughkeepsie, NY 12604-0484, USA.
authors.forename: Miriam
authors.identifier: 0000-0001-9609-474X
authors.initials: M
authors.lastname: Rossi
authors.affiliation: Department of Neuroinflammation, University College London Institute of Neurology, 1 Wakefield Street, London WC1N 1PK, UK.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Pocock
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D047188:Chalcones / Q000494:pharmacology*; D018925:Chemokines / Q000378:metabolism; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D000066829:Neuroprotection / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D047188:Chalcones; D018925:Chemokines; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D051197:Toll-Like Receptor 4