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铝诱导的分子神经退行性变:染料木黄酮和鹰嘴豆提取物的保护作用。

Aluminum-induced molecular neurodegeneration: The protective role of genistein and chickpea extract.

作者信息

Wahby M M, Mohammed D S, Newairy A A, Abdou H M, Zaky A

机构信息

Department of Biochemistry, Faculty of Science, Alexandria University, Egypt.

Department of Biochemistry, Faculty of Science, Alexandria University, Egypt.

出版信息

Food Chem Toxicol. 2017 Sep;107(Pt A):57-67. doi: 10.1016/j.fct.2017.05.044. Epub 2017 May 24.

Abstract

Neurotoxicity of Al is well established and linked to oxidative damage and neurodegeneration. This study investigated the protective role of genistein (Gen) and chickpea extract (CPE) against AlCl-induced neurodegeneration. HPLC analysis revealed that biochanin A-7-O-β-D-glucoside and biochanin A are the major components of the CPE. Gene expression of TNF-α, APP, BACE1, PSEN-2 and ER-β were assessed in brain extract using RT-PCR. Also, NF-кB subunit P65 and COX-2 expression were evaluated by western blotting. The cholinergic function, histological examination and oxidative status were also estimated. The AlCl significantly up regulated the expression of the NF-кB subunit P65, COX-2, TNF- α, BACE1and APP while it significantly down regulated PSEN-2 and ER-β expression. The activity of acetyl cholinesterase (AChE) and the oxidative stress parameters as well as the histological examination confirmed the deleterious effect of AlCl. The administration of either CPE or Gen attenuated the expression of inflammatory cytokines, inhibited the amyloidogenesis and restored both the AChE activity and ER-β expression. Gen and CPE also inhibited the oxidative stress and ameliorated the histological alterations. Accordingly, the present study provides an insight on the molecular role of Gen and CPE as protective agents against neuronal injury.

摘要

铝的神经毒性已得到充分证实,且与氧化损伤和神经退行性变有关。本研究调查了染料木黄酮(Gen)和鹰嘴豆提取物(CPE)对氯化铝诱导的神经退行性变的保护作用。高效液相色谱分析显示,鹰嘴豆提取物的主要成分是鹰嘴豆芽素A - 7 - O-β - D - 葡萄糖苷和鹰嘴豆芽素A。使用逆转录 - 聚合酶链反应(RT - PCR)评估脑提取物中肿瘤坏死因子 - α(TNF - α)、淀粉样前体蛋白(APP)、β - 分泌酶1(BACE1)、早老素2(PSEN - 2)和雌激素受体β(ER - β)的基因表达。此外,通过蛋白质印迹法评估核因子κB亚基P65(NF - κB subunit P65)和环氧合酶 - 2(COX - 2)的表达。还评估了胆碱能功能、组织学检查和氧化状态。氯化铝显著上调了NF - κB亚基P65、COX - 2、TNF - α、BACE1和APP的表达,同时显著下调了PSEN - 2和ER - β的表达。乙酰胆碱酯酶(AChE)活性、氧化应激参数以及组织学检查证实了氯化铝的有害作用。给予CPE或Gen均可减弱炎性细胞因子的表达,抑制淀粉样蛋白生成,并恢复AChE活性和ER - β表达。Gen和CPE还可抑制氧化应激并改善组织学改变。因此,本研究深入探讨了Gen和CPE作为神经元损伤保护剂的分子作用。

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