title: Anti-inflammatory effect of acetylpuerarin on eicosanoid signaling pathway in primary rat astrocytes.
abstract: Astrocytes activation has been implicated in the inflammatory responses underlying brain injury and neurodegenerative diseases including bacterial infections, cerebral ischemia, and Parkinson's diseases. Acetylpuerarin is a newly modified isoflavone based on puerarin that has neuroprotective and antioxidant effects. In this study, we investigated the anti-inflammatory action of acetylpuerarin in regulating the eicosanoids generation and its underlying molecular mechanisms in lipopolysaccharide (LPS)-induced production of arachidonic acid (AA) metabolites in primary rat astrocytes. The results showed that acetylpuerarin concentration dependently inhibited the LPS-induced production of AA metabolites such as prostaglandin E2 (PGE2) and leukotriene C4 (LTC4), and acetylpuerarin significantly attenuated the expression and immunoreactivity of group V secretory phospholipase A2 (sPLA2) protein induced by LPS in astrocytes. Furthermore, in astrocytes pretreated with acetylpuerarin, the time course of phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and of cytosolic PLA2 alpha (cPLA2α) and expression of transcription factors, nuclear factor kappa B (NF-κB), was markedly truncated. Acetylpuerarin concentration dependently abolished the LPS-induced expressions of AA-metabolizing enzymes including cyclooxygenase-2 (COX-2) and lipooxygenase-5 (LOX-5). This study indicates that acetylpuerarin inhibited LPS-induced AA-metabolizing enzymes and AA metabolites in astrocytes via downregulation expression of group V sPLA2 and phosphorylation of ERK1/2, cPLA2α, and NF-κB. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of acetylpuerarin.
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, No. 44, Wenhua Xi Road, Jinan, Shandong, 250012, People's Republic of China.
authors.forename: Yanxiao
authors.initials: Y
authors.lastname: Xiang
authors.forename: Xinbing
authors.initials: X
authors.lastname: Wei
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Huiqing
authors.initials: H
authors.lastname: Liu
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Liu
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D017997:Leukotriene C4 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology*; D054497:Phospholipases A2, Secretory / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D015777:Eicosanoids; D007529:Isoflavones; D008070:Lipopolysaccharides; C521069:acetylpuerarin; D017997:Leukotriene C4; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D054497:Phospholipases A2, Secretory; D015232:Dinoprostone
references.citation: Cell Signal. 2010 Oct;22(10):1427-36
references.pmid: 20546888
references.citation: J Biol Chem. 2000 Dec 22;275(51):39823-6
references.pmid: 11031251
references.citation: J Biol Chem. 2005 Nov 25;280(47):38969-75
references.pmid: 16176925
references.citation: Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:95-114
references.pmid: 12432912
references.citation: Nature. 1997 Dec 11;390(6660):618-22
references.pmid: 9403692
references.citation: J Lipid Res. 2008 Apr;49(4):724-37
references.pmid: 18187403
references.citation: J Cell Biol. 1980 Jun;85(3):890-902
references.pmid: 6248568
references.citation: Atherosclerosis. 2010 Oct;212(2):406-13
references.pmid: 20580365
references.citation: J Biol Chem. 1996 Mar 22;271(12):6758-65
references.pmid: 8636097
references.citation: J Immunol. 2000 Sep 1;165(5):2773-82
references.pmid: 10946309
references.citation: J Biol Chem. 2006 Mar 10;281(10):6691-8
references.pmid: 16407308
references.citation: Mol Cell Biochem. 2009 Oct;330(1-2):171-9
references.pmid: 19404720
references.citation: Pharmacol Rev. 2006 Sep;58(3):375-88
references.pmid: 16968946
references.citation: Brain Res. 2007 May 25;1147:95-104
references.pmid: 17397811
references.citation: J Immunol. 2009 Mar 15;182(6):3877-83
references.pmid: 19265167
references.citation: Cytokine. 2010 Apr;50(1):50-7
references.pmid: 20138782
references.citation: Mol Neurobiol. 2014 Feb;49(1):28-38
references.pmid: 23783559
references.citation: Immunol Lett. 2011 Mar 30;135(1-2):136-43
references.pmid: 21040745
references.citation: J Biol Chem. 1993 Jan 15;268(2):839-44
references.pmid: 8419361
references.citation: Nature. 1997 Dec 11;390(6660):622-5
references.pmid: 9403693
references.citation: Ann Rheum Dis. 2003 Jun;62(6):501-9
references.pmid: 12759283
references.citation: Glia. 2007 Apr 1;55(5):453-62
references.pmid: 17203472
references.citation: J Mol Neurosci. 2007 Sep;33(1):94-9
references.pmid: 17901552
references.citation: J Asian Nat Prod Res. 2010 Oct;12(10):843-50
references.pmid: 20924897
references.citation: J Biol Chem. 1998 Jan 2;273(1):606-12
references.pmid: 9417122
references.citation: J Neurol Sci. 2002 Oct 15;202(1-2):13-23
references.pmid: 12220687
references.citation: Neurotoxicology. 2001 Oct;22(5):607-18
references.pmid: 11770882
references.citation: Stroke. 2007 Jun;38(6):1973-9
references.pmid: 17463317
references.citation: J Lipid Res. 2009 Apr;50 Suppl:S40-5
references.pmid: 18987389
references.citation: Immunol Rev. 2004 Oct;201:191-205
references.pmid: 15361242
references.citation: J Lipid Res. 2004 Feb;45(2):205-13
references.pmid: 14657205
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2011 Jul;85(1):29-35
references.pmid: 21530210
references.citation: Glia. 2001 Nov;36(2):180-90
references.pmid: 11596126
references.citation: J Biol Chem. 1997 Jul 4;272(27):16709-12
references.pmid: 9201969
references.citation: BMC Biochem. 2002 Oct 8;3:30
references.pmid: 12370087
references.citation: J Biol Chem. 2004 Apr 16;279(16):16488-94
references.pmid: 14761945
references.citation: J Pharmacol Exp Ther. 2000 Sep;294(3):793-9
references.pmid: 10945826