一种新型香豆素衍生物P492B的抗神经炎症效应分析  

Effect analysis of the anti-neuroinflammatory properties of P492B,a new coumarin derivative

作　　者：蒋艳林 向文静 牙东姗 陈鑫 邓俊刚[1] 廖儒佳 JIANG Yanlin;XIANG Wenjing;YA Dongshan;CHEN Xin;DENG Jungang;LIAO Rujia(Department of Pharmacy,Affiliated Hospital of Guilin Medical University,Guilin 541001,China;Laboratory of Neuroscience,Affiliated Hospital of Guilin Medical University,Guilin 541001,China;Department of Neurology,Guilin People's Hospital,Guilin 541002,China)

机构地区：[1]桂林医学院附属医院药学部,桂林541001 [2]桂林医学院附属医院神经科学实验室,桂林541002 [3]桂林市人民医院神经内科,桂林541001

出　　处：《华夏医学》2024年第4期34-40,共7页Acta Medicinae Sinica

基　　金：广西壮族自治区药品监督管理局药品安全科研项目(桂药监科直属[2023]008号)。

摘　　要：目的研究新型香豆素衍生物P492B对小胶质细胞介导的神经炎症的作用。方法以香豆素为母核,合成新型香豆素衍生物P95B、P613B和P492B。通过MTT法评估P95B、P613B和P492B对SH-SY5Y神经元细胞系细胞活力的影响,筛选最优化合物P492B。构建脂多糖(LPS)诱导的BV-2小胶质细胞神经炎症模型,给予P492B处理后,形态学观察P492B对小胶质细胞活化的影响。Western blot法检测P492B对小胶质细胞释放一氧化氮合成酶(iNOS)蛋白水平的影响。ELISA法检测P492B对小胶质细胞释放的炎症因子TNF-α和IL-6水平的影响,DCFH-DA荧光探针检测P492B对小胶质细胞ROS水平的影响。结果香豆素、P95B和P613B均可剂量依赖性降低神经细胞活力,而P492B对神经细胞活力无显著影响。P492B可显著改善小胶质细胞的活化,并剂量依赖性的显著降低活化的小胶质细胞iNOS蛋白水平、剂量依赖性的显著减少炎症因子TNF-α和IL-6的表达水平、剂量依赖性的显著降低活化的小胶质细胞活性氧水平。结论新型香豆素衍生物P492B可显著抑制小胶质细胞介导的神经炎症,为神经炎症相关疾病的治疗提供新的潜在治疗药物。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-αand 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.

关 键 词：香豆素衍生物 神经炎症 小胶质细胞 神经保护 

分 类 号：R285[医药卫生—中药学]