Mulberroside a protects against ischemic impairment in primary culture of rat cortical neurons after oxygen-glucose deprivation followed by reperfusion
Mulberroside a protects against ischemic impairment in primary culture of rat cortical neurons after oxygen-glucose deprivation followed by reperfusion
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DOI：
10.1002/jnr.23374
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发表时间：
2014-07-01
影响因子：
4.2
通讯作者：
Liang, Xin-Miao
中科院分区：
文献类型：
--
作者：
Wang, Cai-Ping;Zhang, Lu-Zhong;Liang, Xin-Miao
桑皮苷A是一种天然的多羟基二苯乙烯类化合物，在桑树的根和枝条中含量较高。它以其肾保护、降血糖和抗糖尿病作用而闻名。由于其代谢产物氧化白藜芦醇具有抗炎和神经保护作用，我们认为桑苷A可能具有神经保护作用，可用于治疗脑缺血损伤。因此，我们决定在原代培养的大鼠皮层神经元缺氧缺糖再灌注（OGD/R）后，研究桑苷A的药理学特性，评估其对抗缺氧缺血损伤的能力。结果表明，桑苷A引起的神经保护作用与尼莫地平相当。机制研究表明，桑皮苷A降低肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1 β和IL-6的表达，抑制NALP 3、caspase-1和核因子-κ B的活化以及细胞外信号调节蛋白激酶、c-Jun N-末端激酶和p38的磷酸化，表现出抗炎抗凋亡作用。我们的研究结果还进一步表明，促炎细胞因子IL-1 β，IL-6和TNF-α是治疗脑缺血性损伤的有希望的目标。尽管其开发还需要进一步的研究，但所有这些发现使我们推测桑皮苷A是治疗缺血性中风的候选药物，其将作为多因子神经保护剂。(c)2014 Wiley Periodicals，Inc.
Mulberroside A is a natural polyhydroxylated stilbene compound present at relatively high abundance in the roots and twigs of Morus alba L. It is known for its nephroprotective, hypoglycemic, and antidiabetic effects. Because its metabolite, oxyresveratrol, possessed purported anti-inflammatory and neuroprotective effects, we proposed that mulberroside A may elicit neuroprotective effects that can be used in the treatment of brain ischemic injury. Therefore, we decided to investigate the pharmacological properties of mulberroside A in primary culture of rat cortical neurons after oxygen-glucose deprivation followed by reperfusion (OGD/R), evaluating its ability to counteract the hypoxia-ischemia impairment. The results showed that mulberroside A elicited neuroprotective effects comparable to nimodipine. The mechanistic studies showed that mulberroside A decreased the expressions of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6 and inhibited the activation of NALP3, caspase-1, and nuclear factor-kappa B and the phosphorylation of extracellular signal-regulated protein kinases, the c-Jun N-terminal kinase, and p38, exhibiting anti-inflammatory antiapoptotic effects. Our results also further demonstrate that the proinflammatory cytokines of IL-1 beta, IL-6, and TNF-alpha are promising targets for treatment of cerebral ischemic injury. Although further investigation is required for its development, all of these findings led us to speculate that mulberroside A is a candidate for the treatment of ischemic stroke, which would act as a multifactorial neuroprotectant. (c) 2014 Wiley Periodicals, Inc.