OBJECTIVE The aim of the present study was to investigate the effect of cornel iridoid glycoside(CIG)on tau hyperphosphorylation induced by wortmannin(WT)and GF-109203X(GFX)and the underlying mechanisms.METHODS Human ...OBJECTIVE The aim of the present study was to investigate the effect of cornel iridoid glycoside(CIG)on tau hyperphosphorylation induced by wortmannin(WT)and GF-109203X(GFX)and the underlying mechanisms.METHODS Human neuroblastoma SK-N-SH cells were pre-incubated with CIG(50,100,and 200μg·mL-1,respectively)for 24 h,and then exposed to WT 10μmol·L-1 and GFX 10μmol·L-1for 3hafter washing out CIG.Immuno-fluorescence was used to observe the microtubular cytoskeleton of the cultured cells.Western blotting was used to measure the phosphorylation level of tau protein,glycogen synthase kinase 3β(GSK-3β)and protein phosphatase 2A(PP2A).The activity of PP2 Awas detected by a biochemical assay.RESULTS Pre-incubation of CIG significantly attenuated the WT/GFX-induced tau hyperphosphorylation at the sites of Thr205,Thr212,Ser214,Thr217Ser396 and PHF-1,and improved the damage of morphology and microtubular cytoskeleton of the cells.CIG did not prevent the decrease in p-AKT-ser473 and pGSK3β-ser9 induced by WT/GFX.However,CIG significantly elevated the activity of PP2 Aby reducing the demethylation of PP2AC at Leu309 and the ratio of PME-1/LCMT in the WT/GFX-treated cells.CONCLUSION CIG obviously attenuated WT/GFX-induced tau hyper-phosphorylation at multiple AD-related sites by increasing the activity of PP2A.The mechanism may be involved in the reduced demethylation of PP2 Avia down regulating the ratio of PME/LCMT.展开更多
OBJECTIVE In order to investigate whether cornel iridoid glycoside(CIG),the main component extracted from Cornus officinalis,can treat demyelinating diseases of the central nervous system(CNS)such as multiple sclerosi...OBJECTIVE In order to investigate whether cornel iridoid glycoside(CIG),the main component extracted from Cornus officinalis,can treat demyelinating diseases of the central nervous system(CNS)such as multiple sclerosis(MS).METHODS CIG(30,60 and 120mg·kg-1)or vehicle was intragastrically administered once daily to rats,starting immediately after purified myelin basic protein(MBP)68-86 peptides immunization until day 20 post immunization(p.i.).Histopathological staining,enzyme-linked immunosorbent assay,biochemical methods and Western blotting approaches were used to evaluate the disease incidence and severity,neuroinflammatory and neurotrophic response in the CNS.RESULTS Neurological deficit and proportion of incidence seen in EAE rats were significantly reduced by CIG treatment in a dose-dependent manner.Histopathological staining showed that CIG treatment alleviated demyelination and inflammatory infiltration,increased the number of oligodendrocytes,enhanced the expression of brain-derived neurotrophic factor(BDNF).Production of proinflammatory molecules such as interleukin-1β(IL-1β),tumour necrosis factor-αand interferon-γwere also inhibited by CIG administration.CIG could ameliorate phosphorylation of STAT1,STAT3 and JAK1 as well as IL-6/IL-6 Rexpression,which involved in immune response and inflammation.CONCLUSION Our results demonstrated that CIG may ameliorate EAE rats through down-regulation of JAK/STAT signaling pathway.This study gave new insight into the novel regulatory mechanism of CIG and highlight novel therapeutic targets and a potential therapeutic agent for the treatment of MS.展开更多
基金The project supported by National Natural Science Foundation of China(81274120,81273498)the Beijing Natural Science Foundation(7132110)+1 种基金the Beijing Science and Technology Program(Z131102002813066)the Capital Health Development Scientific Grant(2011-1001-05)
文摘OBJECTIVE The aim of the present study was to investigate the effect of cornel iridoid glycoside(CIG)on tau hyperphosphorylation induced by wortmannin(WT)and GF-109203X(GFX)and the underlying mechanisms.METHODS Human neuroblastoma SK-N-SH cells were pre-incubated with CIG(50,100,and 200μg·mL-1,respectively)for 24 h,and then exposed to WT 10μmol·L-1 and GFX 10μmol·L-1for 3hafter washing out CIG.Immuno-fluorescence was used to observe the microtubular cytoskeleton of the cultured cells.Western blotting was used to measure the phosphorylation level of tau protein,glycogen synthase kinase 3β(GSK-3β)and protein phosphatase 2A(PP2A).The activity of PP2 Awas detected by a biochemical assay.RESULTS Pre-incubation of CIG significantly attenuated the WT/GFX-induced tau hyperphosphorylation at the sites of Thr205,Thr212,Ser214,Thr217Ser396 and PHF-1,and improved the damage of morphology and microtubular cytoskeleton of the cells.CIG did not prevent the decrease in p-AKT-ser473 and pGSK3β-ser9 induced by WT/GFX.However,CIG significantly elevated the activity of PP2 Aby reducing the demethylation of PP2AC at Leu309 and the ratio of PME-1/LCMT in the WT/GFX-treated cells.CONCLUSION CIG obviously attenuated WT/GFX-induced tau hyper-phosphorylation at multiple AD-related sites by increasing the activity of PP2A.The mechanism may be involved in the reduced demethylation of PP2 Avia down regulating the ratio of PME/LCMT.
基金The project supported by National Natural Science Foundation of China(81341088,81001656)Beijing Nova Star Program in Science and Technology(Z12111000250000)
文摘OBJECTIVE In order to investigate whether cornel iridoid glycoside(CIG),the main component extracted from Cornus officinalis,can treat demyelinating diseases of the central nervous system(CNS)such as multiple sclerosis(MS).METHODS CIG(30,60 and 120mg·kg-1)or vehicle was intragastrically administered once daily to rats,starting immediately after purified myelin basic protein(MBP)68-86 peptides immunization until day 20 post immunization(p.i.).Histopathological staining,enzyme-linked immunosorbent assay,biochemical methods and Western blotting approaches were used to evaluate the disease incidence and severity,neuroinflammatory and neurotrophic response in the CNS.RESULTS Neurological deficit and proportion of incidence seen in EAE rats were significantly reduced by CIG treatment in a dose-dependent manner.Histopathological staining showed that CIG treatment alleviated demyelination and inflammatory infiltration,increased the number of oligodendrocytes,enhanced the expression of brain-derived neurotrophic factor(BDNF).Production of proinflammatory molecules such as interleukin-1β(IL-1β),tumour necrosis factor-αand interferon-γwere also inhibited by CIG administration.CIG could ameliorate phosphorylation of STAT1,STAT3 and JAK1 as well as IL-6/IL-6 Rexpression,which involved in immune response and inflammation.CONCLUSION Our results demonstrated that CIG may ameliorate EAE rats through down-regulation of JAK/STAT signaling pathway.This study gave new insight into the novel regulatory mechanism of CIG and highlight novel therapeutic targets and a potential therapeutic agent for the treatment of MS.
