%0 Journal Article
%T Gastrodin Inhibits Expression of Inducible NO Synthase, Cyclooxygenase-2 and Proinflammatory Cytokines in Cultured LPS-Stimulated Microglia via MAPK Pathways
%A Ji-Nan Dai
%A Yi Zong
%A Lian-Mei Zhong
%A Yue-Min Li
%A Wei Zhang
%A Li-Gong Bian
%A Qing-Long Ai
%A Yi-Dan Liu
%A Jun Sun
%A Di Lu
%J PLOS ONE
%D 2011
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0021891
%X Background Microglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory enzymes and proinflammatory cytokines. The phenolic glucoside gastrodin, a main constituent of a Chinese herbal medicine, has been known to display anti-inflammatory properties. The current study investigates the potential mechanisms whereby gastrodin affects the expression of potentially pro-inflammatory proteins by cultured murine microglial BV-2 cells stimulated with lipopolysaccharide (LPS). Methodology/Principal Findings BV-2 cells were pretreated with gastrodin (30, 40, and 60 米M) for 1 h and then stimulated with LPS (1 米g/ml) for another 4 h. The effects on proinflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and proinflammatory cytokines, tumor necrosis factor-汐 (TNF-汐), and interleukin-1汕 (IL-1汕), are analysed by double-immunofluorescence labeling and RT-PCR assay. To reveal the mechanisms of action of gastrodin we investigated the involvement of mitogen-activated protein kinases (MAPKs) cascades and their downstream transcription factors, nuclear factor-百B (NF-百B) and cyclic AMP-responsive element (CRE)-binding protein (CREB). Gastrodin significantly reduced the LPS-induced protein and mRNA expression levels of iNOS, COX-2, TNF-汐, IL-1汕 and NF-百B. LPS (1 米g/ml, 30 min)-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) and this was inhibited by pretreatment of BV-2 cells with different concentrations of gastrodin (30, 40, and 60 米M). In addition, gastrodin blocked LPS-induced phosphorylation of inhibitor 百B-汐 (I百B-汐) (and hence the activation of NF-百B) and of CREB, respectively. Conclusion and Implications This study indicates that gastrodin significantly attenuate levels of neurotoxic proinflammatory mediators and proinflammatory cytokines by inhibition of the NF-百B signaling pathway and phosphorylation of MAPKs in LPS-stimulated microglial cells. Arising from the above, we suggest that gastrodin has a potential as an anti-inflammatory drug candidate in neurodegenerative diseases.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0021891