中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Cycloastragenol upregulates SIRT1 expression, attenuates apoptosis and suppresses neuroinflammation after brain ischemia

文献类型:期刊论文

作者Li, Man2,3; Li, Shi-chun2,3; Dou, Bao-kai2,3; Zou, Ying-xiang2,3; Han, Hao-zhen1,4; Liu, Dong-xiang1,4; Ke, Zun-ji3; Wang, Zhi-fei2,3
刊名ACTA PHARMACOLOGICA SINICA
出版日期2020-03-16
页码8
关键词cycloastragenol SIRT1 apoptosis neuroinflammation cerebral ischemia
ISSN号1671-4083
DOI10.1038/s41401-020-0386-6
通讯作者Wang, Zhi-fei(zfwang@shutcm.edu.cn)
英文摘要Cycloastragenol (CAG) is the active form of astragaloside IV isolated from Astragalus Radix, which displays multiple pharmacological effects. Silent information regulator 1 (SIRT1), a class III histone deacetylase, has been shown to play an important role in neuroprotection against cerebral ischemia. In this study, we investigated whether CAG protected against ischemic brain injury and, if so, whether the beneficial effects were associated with the regulation of SIRT1 in the ischemic brain. Mice were subjected to 45 min of middle cerebral artery occlusion (MCAO) followed by reperfusion. CAG (5, 10, 20 mg/kg) was injected intraperitoneally at the onset of reperfusion, 12 h later and then twice daily for up to three days. CAG dose-dependently reduced brain infarct volume, significantly ameliorated functional deficits, and prevented neuronal cell loss in MCAO mice. Meanwhile, CAG significantly reduced matrix metalloproteinase-9 activity, prevented tight junction degradation and subsequently ameliorated blood-brain barrier disruption. Moreover, CAG significantly upregulated SIRT1 expression in the ischemic brain but did not directly activate its enzymatic activity. Concomitant with SIRT1 upregulation, CAG reduced p53 acetylation and the ratio of Bax to Bcl-2 in the ischemic brain. CAG also inhibited NF-kappa B p65 nuclear translocation. As a result, CAG suppressed the mRNA expression of pro-inflammatory cytokines, including TNF-alpha and IL-1 beta, and inhibited the activation of microglia and astrocytes in the ischemic brain. Our findings suggest that CAG is neuroprotective against ischemic brain injury in mice and that its beneficial effect may involve SIRT1 upregulation and the inhibition of apoptosis and neuroinflammation in the ischemic brain.
WOS关键词ASTRAGALOSIDE IV ; RAT MODEL ; INHIBITION ; TRANSCRIPTION ; METABOLISM ; PROTECTS ; SIRTUINS ; DAMAGE ; P53
资助项目National Natural Science Foundation of China[81873029]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000519839800001
出版者NATURE PUBLISHING GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/281142]  
专题中国科学院上海药物研究所
通讯作者Wang, Zhi-fei
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol 3, Shanghai 201203, Peoples R China
2.Shanghai Univ Tradit Chinese Med, Sch Basic Med Sci, Shanghai 201203, Peoples R China
3.Shanghai Univ Tradit Chinese Med, Acad Integrat Med, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714
Li, Man,Li, Shi-chun,Dou, Bao-kai,et al. Cycloastragenol upregulates SIRT1 expression, attenuates apoptosis and suppresses neuroinflammation after brain ischemia[J]. ACTA PHARMACOLOGICA SINICA,2020:8.
APA Li, Man.,Li, Shi-chun.,Dou, Bao-kai.,Zou, Ying-xiang.,Han, Hao-zhen.,...&Wang, Zhi-fei.(2020).Cycloastragenol upregulates SIRT1 expression, attenuates apoptosis and suppresses neuroinflammation after brain ischemia.ACTA PHARMACOLOGICA SINICA,8.
MLA Li, Man,et al."Cycloastragenol upregulates SIRT1 expression, attenuates apoptosis and suppresses neuroinflammation after brain ischemia".ACTA PHARMACOLOGICA SINICA (2020):8.

入库方式: OAI收割

来源:上海药物研究所

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