Open AccessGua Lou Gui Zhi decoction suppresses LPS-induced activation of the TLR4/NF-κB pathway in BV-2 murine microglial cells
Author(s) -
Hongbo Hu,
Zuanfang Li,
Xiaodong Zhu,
Ren Lin,
Jiumao Lin,
Jun Peng,
Jing Tao,
Lidian Chen
Publication year - 2013
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2013.1331
Subject(s) - tlr4 , nf κb , microglia , neuroinflammation , pharmacology , iκbα , tumor necrosis factor alpha , inflammation , signal transduction , apoptosis , nfkb1 , nitric oxide , lipopolysaccharide , cancer research , neuroprotection , biology , immunology , microbiology and biotechnology , chemistry , endocrinology , transcription factor , biochemistry , gene
Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling-mediated neuroinflammation contributes to secondary brain damage in ischemic stroke; therefore, anti-inflammatory therapy via suppression of the TLR4/NF-κB pathway could be a promising strategy for the treatment of stroke and post-stroke disabilities. Gua Lou Gui Zhi decoction (GLGZD) has long been used in China to clinically treat dysfunction after stroke such as muscular spasticity, but the precise mechanisms are largely unknown. In the present study, we evaluated the anti-inflammatory effect of GLGZD and investigated the underlying molecular mechanisms using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells as an in vitro inflammatory model of neural cells. We found that GLGZD inhibited the inflammatory response in microglial cells as it significantly reduced LPS-induced expression of pro-inflammatory nitric oxide, tumour necrosis factor-α, interleukin (IL)-6 and IL-1β in BV-2 cells, in a dose-dependent manner. In addition, GLGZD treatment significantly decreased the protein expression of TLR4 and myeloid differentiation factor 88, inhibited the phosphorylation of IκB and blocked the nuclear translocation of NF-κB in BV-2 cells, demonstrating its inhibitory effect on the activation of TLR4/NF-κB signaling. Collectively, our findings suggest that inhibition of the inflammatory response via suppression of the TLR4/NF-κB pathway may be one of the mechanisms through which GLGZD ameliorates the damage in ischemic cerebral tissues.