title: Pycnogenol Attenuates the Release of Proinflammatory Cytokines and Expression of Perilipin 2 in Lipopolysaccharide-Stimulated Microglia in Part via Inhibition of NF-κB and AP-1 Activation.
abstract: Over activation of microglia results in the production of proinflammatory agents that have been implicated in various brain diseases. Pycnogenol is a patented extract from French maritime pine bark (Pinus pinaster Aiton) with strong antioxidant and anti-inflammatory potency. The present study investigated whether pycnogenol may be associated with the production of proinflammatory mediators in lipopolysaccharide-stimulated BV2 (mouse-derived) microglia. It was found that pycnogenol treatment was dose-dependently associated with significantly less release of nitricoxide (NO), TNF-α, IL-6 and IL-1β, and lower levels of intercellular adhesion molecule1 (ICAM-1) and perilipin 2 (PLIN2). Furthermore, this effect was replicated in primary brain microglia. Levels of inducible NO synthase mRNA and protein were attenuated, whereas there was no change in the production of the anti-inflammatory cytokine IL-10. Further evidence indicated that pycnogenol treatment led to the suppression of NF-κB activation through inhibition of p65 translocation into the nucleus and inhibited DNA binding of AP-1, suggesting that these proinflammatory factors are associated with NF-κB and AP-1. We conclude that pycnogenol exerts anti-inflammatory effects through inhibition of the NF-κB and AP-1pathway, and may be useful as a therapeutic agent in the prevention of diseases caused by over activation of microglia.
authors.affiliation: Department of Neurology, Shengjing Hospital, China Medical University, Shenyang, 110004, P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Fan
authors.affiliation: Department of Neurology, Shengjing Hospital, China Medical University, Shenyang, 110004, P. R. China.
authors.forename: Sai-Hong
authors.initials: SH
authors.lastname: Dun
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital, P. R. China Medical University, Shenyang, 110001, P. R. China.
authors.forename: Jian-Qiu
authors.initials: JQ
authors.lastname: Gu
authors.affiliation: Department of Neurology, Shengjing Hospital, China Medical University, Shenyang, 110004, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Clinical Investigation & Department of Endocrine, Metabolic and Rheumatic Diseases, Oita San-ai Medical center, Oita, 870-1151, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Ikuyama
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D000070780:Perilipin-2; D010936:Plant Extracts; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D005419:Flavonoids; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D000070780:Perilipin-2; D010936:Plant Extracts; C000602983:Plin2 protein, mouse; D018808:Transcription Factor AP-1; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; C024070:pycnogenols; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse