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 |
| 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. |
| 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
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。