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(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.
