Alzheimer's disease(AD)shows cognitive impairments in clinic,which is multifactorial with different etiopathogenic mechanisms such as A|3 deposition,neuroinflammation and neuronal dystrophy involved.Therefore,mult...Alzheimer's disease(AD)shows cognitive impairments in clinic,which is multifactorial with different etiopathogenic mechanisms such as A|3 deposition,neuroinflammation and neuronal dystrophy involved.Therefore,multi-targets drugs with neuroprotective,anti-amyloidogenic and anti-inflammatory properties will be effective in AD treatment.Epigallocatechin-3-gallate(EGCG)possesses a broad spectrum of pharmacological activities in the prevention and treatment of multiple neurodegenerative diseases.In the present study,we showed that oral administration of EGCG(50 mg/kg)for 4 months significantly attenuated the cognitive deficits in APP/PS1 transgenic mice,which served as AD model.Moreover,EGCG induced an improvement in dendritic integrity and expression levels of synaptic proteins in the brain of APP/PS 1 mice.And EGCG exerted obvious anti-inflammatory effects,which was manifested by alleviating microglia activation,decreasing pro-inflammatory cytokine(IL-β)and increasing anti-inflammatory cytokines(IL-10,IL-β).Furthermore,p-amyloid(AP)plaques were markedly reduced in the hippocampus of 6-month old APP/PS 1 mice after EGCG treatment.In conclusion,these findings indicate that EGCG improves AD-like cognitive impairments through neuroprotective,anti-amyloidogenic and anti-inflammatory effects,thus is a promising therapeutic can didate for AD.展开更多
以市售1,6,7,12-四氯-3,4,9,10-苝四甲酸二酐（TCPBA）为原料,合成了中间体N,N＇-二（2,6-二异丙基）苯基-1,6,7,12-四氯-3,4,9,10-苝四甲酸二酰亚胺（BDIP-TCPBI）和产品N,N＇-二（2,6-二异丙基）苯基-1,6,7,12-四苯氧基-3,4,9,10-苝...以市售1,6,7,12-四氯-3,4,9,10-苝四甲酸二酐（TCPBA）为原料,合成了中间体N,N＇-二（2,6-二异丙基）苯基-1,6,7,12-四氯-3,4,9,10-苝四甲酸二酰亚胺（BDIP-TCPBI）和产品N,N＇-二（2,6-二异丙基）苯基-1,6,7,12-四苯氧基-3,4,9,10-苝四甲酸二酰亚胺（苝红620）,其结构经IR、MS和NMR进行了确证。结果显示：反应中引入催化剂二水乙酸锌,使BDIP-TCPBI的合成时间缩短了一半,纯度（HPLC,下同）较文献纯度（68%）高出16%,其最佳工艺条件为：n（TCPBA）∶n（2,6-二异丙基苯胺）∶n（二水乙酸锌）∶n（丙酸）=1∶4∶0.2∶107,120℃反应12 h,产率为88%,纯度为84%;使用简便的洗涤代替柱色谱法使苝红620的纯度较文献纯度（82%）高出9%。苝红620的斯托克斯位移值为35 nm,循环伏安法获得苝红620的LUMO和HOMO轨道能级分别为–4.144和–4.470 e V,且具有较小的荧光自吸效应,是一种潜在的电子受体材料。展开更多
基金the National Natural Science Foundation of China(No.31800851).
文摘Alzheimer's disease(AD)shows cognitive impairments in clinic,which is multifactorial with different etiopathogenic mechanisms such as A|3 deposition,neuroinflammation and neuronal dystrophy involved.Therefore,multi-targets drugs with neuroprotective,anti-amyloidogenic and anti-inflammatory properties will be effective in AD treatment.Epigallocatechin-3-gallate(EGCG)possesses a broad spectrum of pharmacological activities in the prevention and treatment of multiple neurodegenerative diseases.In the present study,we showed that oral administration of EGCG(50 mg/kg)for 4 months significantly attenuated the cognitive deficits in APP/PS1 transgenic mice,which served as AD model.Moreover,EGCG induced an improvement in dendritic integrity and expression levels of synaptic proteins in the brain of APP/PS 1 mice.And EGCG exerted obvious anti-inflammatory effects,which was manifested by alleviating microglia activation,decreasing pro-inflammatory cytokine(IL-β)and increasing anti-inflammatory cytokines(IL-10,IL-β).Furthermore,p-amyloid(AP)plaques were markedly reduced in the hippocampus of 6-month old APP/PS 1 mice after EGCG treatment.In conclusion,these findings indicate that EGCG improves AD-like cognitive impairments through neuroprotective,anti-amyloidogenic and anti-inflammatory effects,thus is a promising therapeutic can didate for AD.
文摘以市售1,6,7,12-四氯-3,4,9,10-苝四甲酸二酐（TCPBA）为原料,合成了中间体N,N＇-二（2,6-二异丙基）苯基-1,6,7,12-四氯-3,4,9,10-苝四甲酸二酰亚胺（BDIP-TCPBI）和产品N,N＇-二（2,6-二异丙基）苯基-1,6,7,12-四苯氧基-3,4,9,10-苝四甲酸二酰亚胺（苝红620）,其结构经IR、MS和NMR进行了确证。结果显示：反应中引入催化剂二水乙酸锌,使BDIP-TCPBI的合成时间缩短了一半,纯度（HPLC,下同）较文献纯度（68%）高出16%,其最佳工艺条件为：n（TCPBA）∶n（2,6-二异丙基苯胺）∶n（二水乙酸锌）∶n（丙酸）=1∶4∶0.2∶107,120℃反应12 h,产率为88%,纯度为84%;使用简便的洗涤代替柱色谱法使苝红620的纯度较文献纯度（82%）高出9%。苝红620的斯托克斯位移值为35 nm,循环伏安法获得苝红620的LUMO和HOMO轨道能级分别为–4.144和–4.470 e V,且具有较小的荧光自吸效应,是一种潜在的电子受体材料。
