Castillo Willian Orlando, Aristizabal-Pachon Andres Felipe, Sakamoto-Hojo Elsa, Gasca Cristian Aldemar, Cabezas-Fajardo Fabio Antonio, Takahashi Catarina
Department of Biology, Faculty of Natural Sciences, Exact and Education, University of Cauca, Popayán, Colombia; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia.
Mutat Res Genet Toxicol Environ Mutagen. 2018 Dec;836(Pt B):54-61. doi: 10.1016/j.mrgentox.2018.06.010. Epub 2018 Jun 2.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuritic plaques (NPs), and neurofibrillary tangles (NFTs). β-Amyloid peptide (Aβ) is the principal component of NPs and is associated with oxidative stress, as well as dysfunction of cholinergic neurotransmission system and cell death. Nevertheless, one of the most promising therapeutic approaches for patients with AD is based on the pharmacological intervention to increases acetylcholine levels and reduces oxidative stress in AD brain. Previous studies have indicated that alkaloids from Amaryllidaceae family exhibit a wide range of biological activities. The purpose of this study was to investigate whether C. subedentata extract may modulate Aβ- induced genotoxicity in SH-SY5Y cell line. Here, we conducted a set of bioassays to measure: viability, clonogenic survival, cell death, chromosome damage and DNA strand breaks. The results showed that Aβ significantly inhibited cell viability through necrosis rather than apoptosis, increased the percentage of DNA damage and caused mitochondrial morphological alterations. Treatment with the C. subedentata extract led to a significant recovery of cell survival, decreased necrotic cell death and exerted an induction of antigenotoxic effects; additionally, the extract caigused inhibition of acetylcholinesterase (AChE). The present study confirms neuroprotective activities of C. subedentata belonging Amaryllidaceae family and provide a novel information to clarify the mechanisms by which the extracts decrease DNA damage levels induced by Aβ.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征为神经炎性斑块（NPs）和神经原纤维缠结（NFTs）。β-淀粉样肽（Aβ）是NPs的主要成分，与氧化应激、胆碱能神经传递系统功能障碍及细胞死亡相关。然而，针对AD患者最有前景的治疗方法之一是基于药物干预来提高乙酰胆碱水平并降低AD大脑中的氧化应激。先前的研究表明，石蒜科植物的生物碱具有广泛的生物活性。本研究的目的是调查浅裂玉凤花提取物是否能调节Aβ诱导的SH-SY5Y细胞系的遗传毒性。在此，我们进行了一系列生物测定以测量：活力、克隆形成存活率、细胞死亡、染色体损伤和DNA链断裂。结果表明，Aβ通过坏死而非凋亡显著抑制细胞活力，增加DNA损伤百分比并导致线粒体形态改变。用浅裂玉凤花提取物处理可显著恢复细胞存活，减少坏死性细胞死亡并发挥抗原毒性作用；此外，该提取物可抑制乙酰胆碱酯酶（AChE）。本研究证实了石蒜科浅裂玉凤花的神经保护活性，并为阐明该提取物降低Aβ诱导的DNA损伤水平的机制提供了新信息。
