关键词: H2O2-induced oxidative stress in SH-SY5Y anti-Aβ fibrilization/oligomerization anti-acetylcholine esterase activity apiole carvone dill neuroprotection

Mesh : Humans Neuroprotective Agents / pharmacology chemistry Cell Line, Tumor Plant Extracts / pharmacology chemistry Neuroblastoma / metabolism drug therapy pathology Oxidative Stress / drug effects Anethum graveolens / chemistry Seeds / chemistry Membrane Potential, Mitochondrial / drug effects Amyloid beta-Peptides / metabolism Lipid Peroxidation / drug effects Reactive Oxygen Species / metabolism Hydrogen Peroxide Phytochemicals / pharmacology chemistry Cell Survival / drug effects Acetylcholinesterase / metabolism

来  源:   DOI:10.3390/ijms25137104   PDF(Pubmed)

Abstract:
Neurodegeneration diseases (NDs) are a group of complex diseases primarily characterized by progressive loss of neurons affecting mental function and movement. Oxidative stress is one of the factors contributing to the pathogenesis of NDs, including Alzheimer\'s disease (AD). These reactive species disturb mitochondrial function and accelerate other undesirable conditions including tau phosphorylation, inflammation, and cell death. Therefore, preventing oxidative stress is one of the imperative methods in the treatment of NDs. To accomplish this, we prepared hexane and ethyl acetate extracts of Anethum graveolens (dill) and identified the major phyto-components (apiol, carvone, and dihydrocarvone) by GC-MS. The extracts and major bioactives were assessed for neuroprotective potential and mechanism in hydrogen peroxide-induced oxidative stress in the SH-SY5Y neuroblastoma cell model and other biochemical assays. The dill (extracts and bioactives) provided statistically significant neuroprotection from 0.1 to 30 µg/mL by mitigating ROS levels, restoring mitochondrial membrane potential, reducing lipid peroxidation, and reviving the glutathione ratio. They moderately inhibited acetylcholine esterase (IC50 dill extracts 400-500 µg/mL; carvone 275.7 µg/mL; apiole 388.3 µg/mL), displayed mild anti-Aβ1-42 fibrilization (DHC 26.6%) and good anti-oligomerization activity (>40% by dill-EA, carvone, and apiole). Such multifactorial neuroprotective displayed by dill and bioactives would help develop a safe, low-cost, and small-molecule drug for NDs.
摘要:
神经变性疾病(ND)是一组复杂的疾病,其主要特征是影响精神功能和运动的神经元进行性丧失。氧化应激是导致NDs发病的因素之一,包括阿尔茨海默病(AD)。这些反应性物质干扰线粒体功能并加速其他不良条件,包括tau磷酸化,炎症,细胞死亡。因此,预防氧化应激是治疗NDs的必要方法之一。要做到这一点,我们制备了Anethumgraveolens(dill)的己烷和乙酸乙酯提取物,并鉴定了主要的植物成分(piol,Carvone,和二氢香芹酮)通过GC-MS。在SH-SY5Y神经母细胞瘤细胞模型和其他生化测定中,评估了提取物和主要生物活性物质在过氧化氢诱导的氧化应激中的神经保护潜力和机制。通过降低ROS水平,从0.1到30µg/mL的dill(提取物和生物活性物质)提供了统计学上显著的神经保护作用,恢复线粒体膜电位,减少脂质过氧化,恢复谷胱甘肽的比例。他们适度抑制乙酰胆碱酯酶(IC50dill提取物400-500µg/mL;香芹酮275.7µg/mL;apiole388.3µg/mL),表现出温和的抗Aβ1-42纤维化(DHC26.6%)和良好的抗低聚活性(>40%通过dill-EA,Carvone,和apiole)。这种由dill和生物活性物质显示的多因素神经保护作用将有助于开发一种安全的,低成本,和NDS的小分子药物。
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