title: Neuroprotection of Scutellarin is mediated by inhibition of microglial inflammatory activation.
abstract: Inhibition of microglial over-reaction and the inflammatory processes may represent a therapeutic target to alleviate the progression of neurological diseases, such as neurodegenerative diseases and stroke. Scutellarin is the major active component of Erigeron breviscapus (Vant.) Hand-Mazz, a herbal medicine in treatment of cerebrovascular diseases for a long time in the Orient. In this study, we explored the mechanisms of neuroprotection by Scutellarin, particularly its anti-inflammatory effects in microglia. We observed that Scutellarin inhibited lipopolysaccharide (LPS)-induced production of proinflammatory mediators such as nitric oxide (NO), tumor necrosis factor α (TNFα), interleukin-1β (IL-1β) and reactive oxygen species (ROS), suppressed LPS-stimulated inducible nitric oxide synthase (iNOS), TNFα, and IL-1β mRNA expression in rat primary microglia or BV-2 mouse microglial cell line. Scutellarin inhibited LPS-induced nuclear translocation and DNA binding activity of nuclear factor κB (NF-κB). It repressed the LPS-induced c-Jun N-terminal kinase (JNK) and p38 phosphorylation without affecting the activity of extracellular signal regulated kinase (ERK) mitogen-activated protein kinase. Moreover, Scutellarin also inhibited interferon-γ (IFN-γ)-induced NO production, iNOS mRNA expression and transcription factor signal transducer and activator of transcription 1α (STAT1α) activation. Concomitantly, conditioned media from Scutellarin pretreated BV-2 cells significantly reduced neurotoxicity compared with conditioned media from LPS treated alone. Together, the present study reported the anti-inflammatory activity of Scutellarin in microglial cells along with their underlying molecular mechanisms, and suggested Scutellarin might have therapeutic potential for various microglia mediated neuroinflammation.
authors.affiliation: Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Guo
authors.forename: L
authors.initials: L
authors.lastname: Kang
authors.forename: X
authors.initials: X
authors.lastname: Gao
authors.forename: L
authors.initials: L
authors.lastname: Hu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D047310:Apigenin / Q000494:pharmacology*; D001921:Brain / Q000166:cytology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005965:Glucuronates / Q000494:pharmacology*; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000737:chemistry / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D005965:Glucuronates; D050832:Interferon-Stimulated Gene Factor 3; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C079868:gamma interferon activation factor; C484876:scutellarin; D009569:Nitric Oxide; D047310:Apigenin; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases