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Honokiol Attenuates Amyloid‐beta Induced Neuroinflammatory Microglial Polarization in BV2 Microglial Cells
Author(s) -
Jones Ellery,
Govindarajulu Manoj,
Ramesh Sindhu,
Dhanasekaran Murali
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.501.5
Subject(s) - honokiol , microglia , neuroinflammation , ampk , proinflammatory cytokine , tumor necrosis factor alpha , chemistry , protein kinase a , microbiology and biotechnology , inflammation , kinase , pharmacology , immunology , biology
Neuroinflammation plays a crucial role in the pathogenesis of Alzheimer's Disease (AD). Microglia are the macrophages of the central nervous system (CNS), which play a crucial role in immune surveillance and maintaining homeostasis. Chronic microglial activation is detrimental because they produce several pro‐inflammatory cytokines, which result in neuronal cell death (M1 phenotype). Additionally, several studies indicate that anti‐inflammatory mechanisms are down‐regulated in AD (M2 phenotype). Honokiol is a lipophilic polyphenol known to possess potent anti‐inflammatory properties. The goal of this study was to determine the effect of honokiol on activated microglia. The microglial cell line BV2 was pretreated with Honokiol, followed by treatment with amyloid beta, for 24 hours. Pro‐inflammatory activation was assessed by measuring nitric oxide, TNF‐α and IL‐6 levels. Biochemical assays, including western blot, immunocytochemistry and PCR, were performed to mechanistically determine the effect of honokiol on microglial activation. Honokiol significantly reduced NO, ROS, TNF‐α and IL‐6 levels. Honokiol also significantly reduced iNOS expresssion, down‐regulated markers of M1 phenotype and increased M2 markers. The promotional effects of Honokiol on M2 polarization were attenuated by an AMP‐activated protein kinase (AMPK) inhibitor, indicating that AMPK activation participates in Honokiol's effects. Furthermore, Honokiol‐mediated M2 gene expression was prevented by an inhibitor of calmodulin‐dependent protein kinase kinase β (CaMKKβ), an upstream kinase of AMPK. Our in vitro studies indicate that Honokiol could be acting as an AMPK activator, thereby enhancing M2 polarization and suppressing microglial activation. Further studies in animal models need to be conducted to validate Honokiol as a novel and safe therapeutic compound for the treatment of neuroinflammation associated with AD. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .