title: Anti-inflammatory role of the isoflavone diadzein in lipopolysaccharide-stimulated microglia: implications for Parkinson's disease.
abstract: Microglial activation and subsequent release of toxic pro-inflammatory factors are believed to play an important role in neuronal cell death associated with Parkinson's disease (PD). Compounds that inhibit microglia activation and suppress pro-inflammatory factor release have been reported to have neuroprotective effects in animal models of PD. In this study, we tested whether diadzein, a natural isoflavone found in soybean, attenuated lipopolysaccharide (LPS)-induced release of inflammatory mediators in BV-2, a murine microglial cell line. Diadzein pretreatment was found to significantly suppress the production of the pro-inflammatory factors nitric oxide and IL-6 as well as their mRNA expression in conjunction with reductions in ROS production, p38 MAPK phosphorylation, and NF-κB activation. Furthermore, transfer of conditioned media (CM) from BV-2 cells pretreated with diadzein resulted in a significantly reduction in dopaminergic neurotoxicity compared with CM from microglia stimulated with LPS alone. Together, our results suggest that diadzein's neuroprotective properties may be due to its ability to dampen induction of microglial activation and the subsequent release of soluble pro-inflammatory factors. This appears to be via inhibition of oxidative induction of the p38 MAP kinase-NFκB pathway, resulting in reduced expression of pro-inflammatory genes and release of their corresponding gene products.
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA.
authors.forename: Shankar J
authors.initials: SJ
authors.lastname: Chinta
authors.forename: Abirami
authors.initials: A
authors.lastname: Ganesan
authors.forename: Pedro
authors.initials: P
authors.lastname: Reis-Rodrigues
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Lithgow
authors.forename: Julie K
authors.initials: JK
authors.lastname: Andersen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002452:Cell Count; D002461:Cell Line, Transformed; D017077:Culture Media, Conditioned / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007529:Isoflavones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000469:parasitology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection / Q000379:methods; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D000893:Anti-Inflammatory Agents; D017077:Culture Media, Conditioned; D051546:Cyclooxygenase 2; D016207:Cytokines; D004298:Dopamine; D007529:Isoflavones; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases; D000097782:NF-kappaB-Inducing Kinase; C004742:daidzein; C489691:Ptgs2 protein, rat