The Protective Effects of Panax notoginseng Saponin on the Blood-Brain Barrier via the Nrf2/ARE Pathway in bEnd3 Cells
The Protective Effects of Panax notoginseng Saponin on the Blood-Brain Barrier via the Nrf2/ARE Pathway in bEnd3 Cells
复制标题
三七皂苷通过 Nrf2/ARE 通路对 bEnd3 细胞血脑屏障的保护作用
DOI：
10.59720/15-074
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Ningna Zhou
中科院分区：
文献类型：
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作者：
Jinting Yang;Ningna Zhou
脑微血管内皮细胞(CMECs)是血脑屏障(BBB)的主要组成部分，血脑屏障是物质选择性扩散到脑内的关键决定因素。氧化应激对中脑微血管内皮细胞的损伤可导致血脑屏障的破坏，与神经系统疾病有关。Nrf2/ARE通路的激活是抵抗氧化应激所致细胞损伤的最重要的内源性防御机制之一。因此，激活Nrf2/ARE通路的物质是潜在的神经保护剂。我们研究了三七叶总皂苷(LPNS)对氧化应激诱导的小鼠脑微血管内皮细胞株bEnd3细胞损伤的保护作用。乳酸脱氢酶检测表明，LPN对H-₂-O-₂诱导的细胞死亡具有浓度和时间依赖性的保护作用。10μg/mLLPN作用于bEnd3细胞24 h，显著增加紧密连接蛋白claudin-1和claudin-5的表达，激活Nrf2(核转位)，上调Nrf2‘S下游抗氧化剂基因，包括血红素加氧酶1(HO-1，Hmox1基因)和NAD(P)H：苯醌氧化还原酶1(NQO-1)。本研究首次证实了LPN对CMECs的保护作用涉及Nrf2/ARE通路的激活，提示LPN可能成为治疗神经系统疾病的潜在候选药物。
Cerebral microvascular endothelial cells (CMECs) are the main component of the blood-brain barrier (BBB), a critical determinant in the selective diffusion of substances into the brain. The injury of CMECs by oxidative stress contributes to BBB disruption, which is related to neurological diseases. Activation of the Nrf2/ARE pathway is one of the most critical endogenous defense mechanisms against cellular damage caused by oxidative stress. Substances that activate the Nrf2/ARE pathway are therefore potential neuroprotectants. We investigated the potential protective effects of the total saponins in the leaves of Panax notoginseng (LPNS) on oxidative-stress-induced damage in bEnd3 cells (a mouse cerebral microvascular endothelial cell line). Lactate dehydrogenase (LDH) assays indicated that LPNS protects against H₂O₂-induced cell death in both a concentration- and time-dependent manner. Pretreatment of bEnd3 cells with 10 μg/mL LPNS for 24 h significantly increased expression of the tight junction proteins claudin-1 and claudin-5, activated Nrf2 (shown by nuclear translocation), and up-regulated Nrf2’s downstream antioxidant genes including heme oxygenase1 (HO-1, HMOX1 gene) and NAD(P)H:quinone oxidoreductase 1 (NQO-1). This study demonstrates for the first time that the protective effects of LPNS on CMECs involve the activation of the Nrf2/ARE pathway and indicate that LPNS may be a potential therapeutic candidate for treating neurological diseases.