NEUROPROTECTION OF SCUTELLARIN IS MEDIATED BY INHIBITION OF MICROGLIAL INFLAMMATORY ACTIVATION

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 alpha (TNF alpha), interleukin-1 beta (IL-1 beta) and reactive oxygen species (ROS), suppressed LPS-stimulated inducible nitric oxide synthase (iNOS), TNF alpha, and IL-1 beta 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 kappa B (NF-kappa B). 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-gamma (IFN-gamma)-induced NO production, iNOS mRNA expression and transcription factor signal transducer and activator of transcription la (STAT1 alpha) 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 neuro-inflammation. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.