title: Honokiol inhibits the inflammatory reaction during cerebral ischemia reperfusion by suppressing NF-κB activation and cytokine production of glial cells.
abstract: 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 (0.7-70μg/kg) significantly reduced brain water contents and decreased the exudation of Evans blue dye from brain capillaries in cerebral IR mice. Honokiol (0.1-10μM) significantly reduced the p65 subunit level of NF-κB in the nucleus of primary culture-microglia. It (0.01-10μM) evidently reduced nitric oxide (NO) level in the microglia culture medium and in the microglia and astrocytes coculture medium. Honokiol (0.01-10μM) significantly decreased the level of TNF-α in the microglia medium or coculture cell medium. Honokiol (10μM) 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-κB activation, consequently blocking the production of inflammatory factors including: NO, tumor necrosis factor-α (TNF-α) and RANTES/CCL5 in glial cells. These results provide evidence for the anti-inflammatory effect of honokiol for the potential treatment of ischemic stroke.
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Shizhong
authors.initials: S
authors.lastname: Chen
authors.forename: Demin
authors.initials: D
authors.lastname: Zhou
authors.forename: Yinye
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D018946:Chemokine CCL5 / Q000096:biosynthesis; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D018946:Chemokine CCL5; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D017705:Lignans; D016328:NF-kappa B; D009569:Nitric Oxide; D014409:Tumor Necrosis Factor-alpha; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols