Cycloastragenol upregulates SIRT1 expression, attenuates apoptosis and suppresses neuroinflammation after brain ischemia

doi:10.1038/s41401-020-0386-6

	Cycloastragenol upregulates SIRT1 expression, attenuates apoptosis and suppresses neuroinflammation after brain ischemia
	Li, Man 1,2; Li, Shi-chun 1,2; Dou, Bao-kai 1,2; Zou, Ying-xiang 1,2; Han, Hao-zhen 3,4; Liu, Dong-xiang 3,4; Ke, Zun-ji 2; Wang, Zhi-fei 1,2
刊名	ACTA PHARMACOLOGICA SINICA
	2020-03-16
页码	8
关键词	cycloastragenol SIRT1 apoptosis neuroinflammation cerebral ischemia
ISSN号	1671-4083
DOI	10.1038/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.
资助项目	National Natural Science Foundation of China[81873029]
WOS关键词	ASTRAGALOSIDE IV ; RAT MODEL ; INHIBITION ; TRANSCRIPTION ; METABOLISM ; PROTECTS ; SIRTUINS ; DAMAGE ; P53
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000519839800001
内容类型	期刊论文
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.Shanghai Univ Tradit Chinese Med, Sch Basic Med Sci, Shanghai 201203, Peoples R China 2.Shanghai Univ Tradit Chinese Med, Acad Integrat Med, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol 3, 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.