Dual anti-ischemic effects of rosmarinic acid n-butyl ester via alleviation of DAPK-p53-mediated neuronal damage and microglial inflammation
Dual anti-ischemic effects of rosmarinic acid n-butyl ester via alleviation of DAPK-p53-mediated neuronal damage and microglial inflammation
复制标题
迷迭香酸正丁酯通过减轻 DAPK-p53 介导的神经元损伤和小胶质细胞炎症的双重抗缺血作用
DOI：
10.1038/aps.2016.156
复制
发表时间：
2017-02
影响因子：
8.2
通讯作者：
Zhang Hai-yan
中科院分区：
文献类型：
--
作者：
Wu Lei;Wang Hong-min;Li Jin-long;Feng Hong-xuan;Zhao Wei-min;Zhang Hai-yan
发现有效的抗缺血药物仍然是一个挑战。最近我们发现迷迭香酸的衍生物迷迭香酸正丁酯(RABE)对缺氧缺糖(OGD)诱导的SH-SY5Y细胞死亡有明显的保护作用。在本研究中，我们同时研究了Rabe对脑缺血、缺血性神经元损伤和小胶质细胞炎症这两个关键因素的影响。RABE(1，10Mol/L)可剂量依赖性地拮抗缺氧或过氧化氢诱导的SH-SY5Y神经母细胞瘤细胞活力的降低。同时，RABE可降低细胞凋亡率，下调促凋亡蛋白Bax和P53的表达，上调抗凋亡蛋白磷酸化死亡相关蛋白激酶(DAPK)的表达。此外，3μ摩尔/L的RABE可明显抑制脂多糖诱导的大鼠小胶质细胞释放α、IL-1β、NO和PGE2，以及诱导型一氧化氮合酶和环氧合酶-2的表达水平。综上所述，这些结果首次揭示了Rabe对神经细胞和神经胶质细胞的潜在抗缺血作用，并阐明了其体外双重益处的分子机制。RABE可能是治疗缺血性中风的一种有前途的药物先导/候选药物。
The discovery of efficacious anti-ischemic drugs remains a challenge. Recently we have found that rosmarinic acid n-butyl ester (RABE), a derivative of rosmarinic acid, significantly protects SH-SY5Y cells against oxygen glucose deprivation (OGD)-induced cell death. In the present study we simultaneously investigated the effects of RABE on the two key players in the pathophysiology of cerebral ischemia, ischemic neuronal damage and microglial inflammation. Pretreatment with RABE (1, 10 μmol/L) dose-dependently attenuated OGD-or H 2 O 2-induced reduction of the viability of SH-SY5Y neuroblastoma cells. RABE pretreatment concurrently reduced the apoptotic cell rate, down-regulated the expression of the pro-apoptotic proteins Bax and p53, and up-regulated the expression of the anti-apoptotic protein phosphorylated death-associated protein kinase (DAPK). Furthermore, pretreatment with RABE (3 μmol/L) markedly inhibited lipopolysaccharide (LPS)-induced increases in the release of TNF-α, IL-1β, NO and PGE 2, and the expression levels of iNOS, and COX-2 in cultured rat microglial cells. In conclusion, these results reveal for the first time the potential anti-ischemic effects of RABE on neuronal and glial cells and elucidate the molecular mechanisms involved in its dual beneficial profiles in vitro. RABE may be a promising drug lead/candidate for the treatment of ischemic stroke.
登录
查看更多内容
DOI：
10.1016/s0749-4041(08)79111-5
发表时间：
2009
期刊：
Yearbook of Vascular Surgery
影响因子：
--
作者：
G. Moneta
通讯作者：
G. Moneta
影响因子：
3.9
作者：
S. Murphy;C. Gibson
通讯作者：
S. Murphy;C. Gibson
DOI：
10.1016/s0513-5117(09)79035-0
发表时间：
2009
期刊：
Yearbook of Neurology and Neurosurgery
影响因子：
--
作者：
A. Rabinstein
通讯作者：
A. Rabinstein
影响因子：
2.1
作者：
Zhang, Lihong;Yu, Wan-hua Amy;Yew, D. T.
通讯作者：
Yew, D. T.
影响因子：
37.8
作者：
Go, Alan S.;Mozaffarian, Dariush;Turner, Melanie B.
通讯作者：
Turner, Melanie B.