title: Paeoniflorin attenuates Aβ1-42-induced inflammation and chemotaxis of microglia in vitro and inhibits NF-κB- and VEGF/Flt-1 signaling pathways.
abstract: Alzheimer׳s disease (AD) is a neurodegenerative disease with elusive pathogenesis, which accounts for most cases of dementia in the aged population. It has been reported that persistent inflammatory responses and excessive chemotaxis of microglia stimulated by beta-amyloid (Aβ) oligomers in the brain may accelerate the progression of AD. The present study was conducted to explore whether paeoniflorin (PF), a water-soluble monoterpene glycoside isolated from the root of Paeonia lactiflora Pallas, could attenuate Aβ1-42-induced toxic effects on primary and BV-2 microglial cells in vitro. Our data showed that PF pretreatment inhibited Aβ1-42-induced production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in rodent microglia. Also, the nuclear translocation of nuclear factor kappa B (NF-κB) subunit p65 and the phosphorylation of NF-κB inhibitor alpha (IκBα) in Aβ1-42-stimulated microglial cells were suppressed by PF administration. Moreover, PF treatment reduced the release of chemokine (C-X-C motif) ligand 1 (CXCL1) and chemokine (C-C motif) ligand 2 (CCL-2) from Aβ1-42-stimulated microglia. Additionally, application of PF inhibited the increases in vascular endothelial growth factor (VEGF) and VEGF receptor 1 (Flt-1) triggered by Aβ1-42, and resulted in a concomitant reduction in microglial chemotaxis. Restoration of VEGF was noted to counteract the inhibitory effect of PF, suggesting that PF mitigated Aβ1-42-elicited microglial migration at least partly by suppressing the VEGF/Flt-1 axis. In summary, in presence of Aβ1-42, PF pretreatment inhibited the excessive microglial activation and chemotaxis.
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110013, China; Department of Neurology, First Affiliated Hospital, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110013, China.
authors.forename: Huayan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110013, China; Department of Immunology, College of Basic Medicine, China Medical University, Shenyang 110013, China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110013, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110013, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110013, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110013, China. Electronic address: xueyixue1@126.com.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects*; D039821:Monoterpenes / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D006027:Glycosides
chemical_list: D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D005960:Glucosides; D039821:Monoterpenes; D016328:NF-kappa B; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; C075222:amyloid beta-protein (1-42); C015423:peoniflorin; D006027:Glycosides
keywords: Alzheimer׳s disease; Beta-amyloid; Chemotaxis; Inflammation; Microglia