Schisandrin B exerts anti-neuroinflammatory activity by inhibiting the Toll-like receptor 4-dependent MyD88/IKK/NF-κB signaling pathway in lipopolysaccharide-induced microglia.
Microglial-mediated neuroinflammation is now considered to be central to the pathogenesis of various neurodegenerative processes, including Alzheimer's disease and Parkinson's disease. Therefore, rational modulation of microglia function to obtain neuroprotective effects is important for the development of safe and effective anti-inflammatory and neuroprotective agents. Here, we investigated the anti-inflammatory and neuroprotective effects, and potential molecular mechanism of action of Schisandrin B (Sch B); which is isolated from the Schizandra fruit (Schisandra chinesnesis). Sch B exerted significant neuroprotective effects against microglial-mediated inflammatory injury in microglia-neuron co-cultures. In addition, Sch B significantly downregulated pro-inflammatory cytokines, including nitrite oxide (NO), tumor necrosis factor (TNF)-α, prostaglandin E(2) (PGE(2)), interleukin (IL)-1β and IL-6. Additionally, Sch B inhibited the interaction of Toll-like receptor 4 with the Toll adapter proteins MyD88, IRAK-1 and TRAF-6 resulting in an inhibition of the IKK/nuclear transcription factor (NF)-κB inflammatory signaling pathway. Furthermore, Sch B inhibited the production of reactive oxygen species (ROS) and NADPH oxidase activity in microglia. In summary, Sch B may exert neuroprotective activity by attenuating the microglial-mediated neuroinflammatory response by inhibiting the TLR4-dependent MyD88/IKK/NF-κB signaling pathway.
Research Studio of Integration of Traditional and Western Medicine, First Hospital, Peking University, Beijing 100034, China.
Ke-Wu
KW
Zeng
Tai
T
Zhang
Hong
H
Fu
Geng-Xin
GX
Liu
Xue-Mei
XM
Wang
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001921:Brain / Q000166:cytology; D016923:Cell Death; D018920:Coculture Techniques; D034242:Cyclooctanes / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D051550:I-kappa B Kinase / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D017705:Lignans / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000893:Anti-Inflammatory Agents; D034242:Cyclooctanes; D053583:Interleukin-1beta; D015850:Interleukin-6; D017705:Lignans; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D018696:Neuroprotective Agents; D011083:Polycyclic Compounds; D017382:Reactive Oxygen Species; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C015499:schizandrin B; D009569:Nitric Oxide; D019255:NADPH Oxidases; D051550:I-kappa B Kinase; D015232:Dinoprostone