Neuroprotective effect of Citrus unshiu immature peel and nobiletin inhibiting hydrogen peroxide-induced oxidative stress in HT22 murine hippocampal neuronal cells.
Neuroprotective effect of Citrus unshiu immature peel and nobiletin inhibiting hydrogen peroxide-induced oxidative stress in HT22 murine hippocampal neuronal cells.
复制标题
DOI：
10.4103/0973-1296.166047
复制
发表时间：
2015-10
影响因子：
0.7
通讯作者：
Choi IY
中科院分区：
文献类型：
--
作者：
Cho HW;Jung SY;Lee GH;Cho JH;Choi IY
氧化应激诱导的细胞损伤在多种神经生物学疾病的病因中很常见，包括阿尔茨海默病和帕金森病。在一项案例研究中，富含川陈皮素的柑橘皮可阻止预先使用多奈哌齐的阿尔茨海默病患者认知障碍的进展。
在本研究中，我们研究了川陈皮素以及温州蜜柑未成熟果皮（CUIP）水提取物（其中川陈皮素为主要成分）对过氧化氢诱导的小鼠海马神经元模型HT22细胞氧化应激的影响及其潜在机制。
在有或无不同浓度的CUIP和川陈皮素存在的情况下，用过氧化氢处理HT22细胞。通过3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基四氮唑溴盐测定法和蛋白质印迹法测量细胞毒性和凋亡蛋白水平。
用CUIP和川陈皮素预处理抑制了过氧化氢导致的细胞死亡。过氧化氢诱导了HT22细胞中磷酸化 - c - Jun氨基末端激酶（p - JNK）和p - p38蛋白的表达；然而，CUIP和川陈皮素在不改变JNK或p38的情况下抑制了p - JNK和p - p38。关于细胞凋亡，测定了半胱天冬酶3、B细胞淋巴瘤2（Bcl - 2）和Bax蛋白的表达。CUIP和川陈皮素抑制了半胱天冬酶3和Bax的表达，但它们诱导了HT22细胞中Bcl - 2的表达。
这些结果表明，CUIP和川陈皮素可通过丝裂原活化蛋白激酶和凋亡途径保护HT22神经元免受过氧化氢诱导的细胞死亡。
Oxidative stress-induced cell damage is common in the etiology of several neurobiological disorders, including Alzheimer's disease and Parkinson's disease. In a case study, nobiletin-rich Citrus reticulata peels could prevent the progression of cognitive impairment in donepezil-preadministered Alzheimer's disease patients. In this study, we investigated the effects and underlying mechanism of nobiletin and Citrus unshiu immature peel (CUIP) water extract, which contains nobiletin as a major compound, on hydrogen peroxide-induced oxidative stress in HT22 cells, a murine hippocampal neuronal model. HT22 cells were treated with hydrogen peroxide in the presence or absence of various concentrations of CUIP and nobiletin. Cytotoxicity and apoptotic protein levels were measured by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and Western blotting. Pretreatment with CUIP and nobiletin inhibited cell death due to hydrogen peroxide. Hydrogen peroxide-induced the expression of phospho-Jun N-terminal kinases (p-JNK) and p-p38 proteins in HT22 cells; however CUIP and nobiletin suppressed p-JNK and p-p38 without changing JNK or p38. Regarding apoptosis, caspase 3, B-cell lymphoma 2 (Bcl-2), and Bax protein expression was determined. CUIP and nobiletin suppressed caspase 3 and Bax expression, but they induced Bcl-2 expression in HT22 cells. These results show that CUIP and nobiletin can protect against hydrogen peroxide-induced cell death in HT22 neurons via mitogen-activated protein kinases and apoptotic pathways.