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Neuroprotective Effects of Triterpenoids from Camellia japonica against Amyloid β-Induced Neuronal Damage.
Journal of Natural Products ( IF 5.1 ) Pub Date : 2020-06-22 , DOI: 10.1021/acs.jnatprod.9b00964
Hyo-Moon Cho 1 , Thi-Kim-Quy Ha 1, 2 , Thi-Phuong Doan 1 , Basanta Dhodary 1 , Jin-Pyo An 1 , Ba-Wool Lee 1 , Jun-Li Yang 3 , Won-Keun Oh 1
Affiliation  

Alzheimer’s disease (AD), a neurocognitive impairment affecting human mental capacity, is related to the accumulation of amyloid-β peptide (Aβ) and the hyperphosphorylation of tau protein. In addition to modern therapies approved for AD treatment, natural products with antioxidant and anti-inflammatory properties have been studied for their potential to prevent AD pathogenesis. Six new noroleanane triterpenoids from the fruit peels of Camellia japonica were isolated, and their structures were determined by diverse spectroscopic methods. The neuroprotective effects of the six new compounds were tested against Aβ-induced neurotoxicity and neuroinflammation in mouse hippocampal and microglial cells. In the model of HT22-transfected cells, compounds 14 showed strongly neuroprotective effects via antioxidant response element gene activation and decreased the level of glutamate uptake. Compounds 14 also appeared to have strong inhibitory effects on NO production in Aβ1–42-transfected BV2 microglial cells. A docking simulation study was used to explain the inhibitory effects of compounds 14 on β-secretase 1 (BACE1). Noroleanane triterpenoids 14 had potential neuroprotective and anti-inflammatory effects against Aβ-induced neuronal damage. The structure–activity relationships of the 30 oleanane triterpenoids from C. japonica were assessed in a model of Aβ1–42-transfected HT22 cells.

中文翻译:

来自山茶花的三萜类化合物对淀粉样蛋白 β 诱导的神经元损伤的神经保护作用。

阿尔茨海默病 (AD) 是一种影响人类智力的神经认知障碍,与淀粉样蛋白 β 肽 (Aβ) 的积累和 tau 蛋白的过度磷酸化有关。除了被批准用于 AD 治疗的现代疗法外,还研究了具有抗氧化和抗炎特性的天然产物预防 AD 发病机制的潜力。从山茶果皮中分离出六种新的降油菜烷三萜,并通过多种光谱方法确定了它们的结构。在小鼠海马和小胶质细胞中测试了六种新化合物对 Aβ 诱导的神经毒性和神经炎症的神经保护作用。在 HT22 转染细胞模型中,化合物14通过抗氧化反应元件基因激活并降低谷氨酸摄取水平显示出强烈的神经保护作用。化合物1 - 4也似乎对NO的产生在Aβ强烈的抑制作用1-42转染的BV2小胶质细胞。一种对接模拟研究中使用来解释化合物的抑制效果1 - 4对β分泌酶1(BACE1)。Noroleanane三萜类化合物1 - 4具有针对Aβ诱导的神经元损害潜在的神经保护和抗炎作用。在 Aβ 1-42模型中评估了来自C. japonica的 30 种齐墩果三萜类化合物的构效关系-转染的HT22细胞。
更新日期:2020-07-24
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