Honokiol inhibits the inflammatory reaction during cerebral ischemia reperfusion by suppressing NF-κB activation and cytokine production of glial cells

This study was designed to investigate the effects of honokiol, a neuroprotective agent, on cerebral edema in cerebral ischemia reperfusion (IR) mice and its mechanism of anti-inflammation. Honokiol (0.7-70 mu g/kg) significantly reduced brain water contents and decreased the exudation of Evans blue dye from brain capillaries in cerebral IR mice. Honokiol (0.1-10 mu M) significantly reduced the p65 subunit level of NF-kappa B in the nucleus of primary culture-microglia. It (0.01-10 mu M) evidently reduced nitric oxide (NO) level in the microglia culture medium and in the microglia and astrocytes coculture medium. Honokiol (0.01-10 mu M) significantly decreased the level of TNF-alpha in the microglia medium or coculture cell medium. Honokiol (10 mu M) decreased the level of Regulated upon Activation Normal T-cell Expressed and Secreted (RANTES/CCL5) protein in medium of microglia or astrocytes. In conclusion, Honokiol has a potent anti-inflammatory effect in cerebral ischemia-reperfusion mice and this effect might be attributed to its inhibition ability on the NF-kappa B activation, consequently blocking the production of inflammatory factors including: NO, tumor necrosis factor-alpha (TNF-alpha) and RANTES/CCL5 in glial cells. These results provide evidence for the anti-inflammatory effect of honokiol for the potential treatment of ischemic (C) 2012 Elsevier Ireland Ltd. All rights reserved.