Effect analysis of the anti-neuroinflammatory properties of P492B,a new coumarin derivative
Objective To investigate the effects of a novel coumarin derivative,P492B,on the microglia-mediated neuroinflammation.Methods Using coumarin as the core structure,new coumarin derivatives P95B,P613B,and P492B were synthesized.The effect of these derivatives on the viability of SH-SY5Y neuronal cells was evaluated using MTT assay,and the optimal compound,P492B,was selected.Next,the neuroinflammation model induced by LPS in BV-2 microglia was established,and the effect of P492B on microglial activation was analyzed through morphological observations.Moreover,the effect of P492B on the expression of iNOS protein in BV-2 microglia was assessed using Western blot analysis.The levels of inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)released by BV-2 microglia were measured using ELISA.The effect of P492B on the level of reactive oxygen species(ROS)in BV-2 microglia was determined using the DCFH-DA fluorescent probe.Results The cell viability of SH-SY5Y cells was significantly reduced in a dose-dependent manner by,P95B,and P613B,while P492B had no significant effect on the cell viability of SH-SY5Y cells.The microglia activation was significantly 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 provids new insights and potential therapeutic options for neuroinflammatory-related diseases.
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