JIANG Yanlin1a , XIANG Wenjing2, YA Dongshan1b , CHEN Xin1a, DENG
Jungang1a, LIAO Rujia1b
( 1. a.Department of Pharmacy, b. Laboratory of Neuroscience, Afiliated Hospital of Guilin Medical University.Guilin 541001, China; 2. Department of
Neurology, Guilin People's Hospital, Guilin 541002, China)
Abstract Objective To investigate the effects of a novel coumarin derivative, P492B, on the microglia-mediatedneuroinfammation, Methods Using coumarin as the core structure, new coumarin derivatives P95B, P613B. and P492B were synthesized. The elfect of these derivatives on the viability of SH-SY5Y neuronal cells was evaluatedusing MTT assay , and the optimal compound, P492B, was selected. Next, the neuroinflammation model induced byLPS in BV-2 microglia was established, and the elfect of P492B on microglial activation was analyzed througmorphological observations. Moreover, the effect of P492B on the expression of iNOS protein in BV-2 microglia wasassessed using Western blot analysis. The levels of inflammatory factors tumor necrosis factor⁃α( TNF⁃α )andinterleukin-6 ( IL-6) released by BV-2 microglia were measured using ELISA. The efect of P492B on the level ofreactive oxygen species ( ROS ) in BV-2 microglia was determined using the DCFH-DA fluorescent probe. ResultsThe cell viability of SH-SY5Y cells was significantly reduced in a dose-dependent manner by, P95B, and P613B while P492B had no significant effeet on the cell viability of SH-SY5Y cells. The microglia activation wassignificantly inhibited by P492B, and the protein level of iNOS of activated microglia was significantly reduced by P492B in dose-dependent manner, The levels of inflammatory factors TNF⁃α and IL-6 were significantly decreased by P492B in dose-dependent manner and the ROS levels in activated microglia was significantly reduced by P492B. Conclusion The novel coumarin derivative, P492B, inhibits microglia-mediated neuroinflammation, which providsnew insights and potential therapeutic options for neuroinflammatory-related diseases.
Keywords: coumarin derivative : neuroinflammation : microglia: neuroprotection
DOI:10.19296/i.cnki.1008-2409.2024-04-005
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