Schisandrin B exerts anti-neuroinflammatory activity by inhibiting the Toll-like receptor 4-dependent MyD88/IKK/NF-κB signaling pathway in lipopolysaccharide-induced microglia

• Published in: European journal of pharmacology 2012-10, Vol.692 (1-3), p.29-37
• Main Authors: Zeng, Ke-Wu, Zhang, Tai, Fu, Hong, Liu, Geng-Xin, Wang, Xue-Mei
• Format: Article
• Language: English
• Subjects: Alzheimer disease; Animals; Anti-Inflammatory Agents - pharmacology; Brain - cytology; Cell Death; Coculture Techniques; Cyclooctanes - pharmacology; Dinoprostone - biosynthesis; Down-Regulation - drug effects; Enzyme Activation - drug effects; I-kappa B Kinase - metabolism; Interleukin-1beta - genetics; interleukin-6; Interleukin-6 - genetics; Lignans - pharmacology; Lipopolysaccharides - pharmacology; Male; mechanism of action; Mice; Microglia; Microglia - cytology; Microglia - drug effects; Microglia - metabolism; Myeloid Differentiation Factor 88 - metabolism; NADP (coenzyme); NADPH Oxidases - metabolism; neuroglia; Neuroinflammation; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Neuroprotection; Neuroprotective Agents - pharmacology; neuroprotective effect; NF-kappa B - metabolism; nitric oxide; Nitric Oxide - biosynthesis; Parkinson disease; pathogenesis; Polycyclic Compounds - pharmacology; prostaglandins; proteins; Rats; Rats, Sprague-Dawley; reactive oxygen species; Reactive Oxygen Species - metabolism; Schisandra; Schisandrin B; signal transduction; Signal Transduction - drug effects; Toll-Like Receptor 4 - metabolism; transcription factors; Tumor Necrosis Factor-alpha - biosynthesis; tumor necrosis factors
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2012.05.030

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 E2 (PGE2), 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.