化学
神经保护
橙皮苷
神经毒性
硫黄素
淀粉样蛋白(真菌学)
程序性细胞死亡
肽
氧化应激
药理学
生物化学
生物物理学
细胞凋亡
细胞外
细胞生物学
毒性
阿尔茨海默病
生物
内科学
医学
无机化学
替代医学
疾病
有机化学
病理
作者
Sakthivel Jafni,S. Sathya,Arunkumar Malaisamy,Chandramohan Kiruthiga,Mahalingam Jeyakumar,Easwaran Murugesh,Kasi Pandima Devi
标识
DOI:10.1016/j.bmc.2023.117536
摘要
In the present study, we evaluated the neuroprotective potential of Hesperidin Methyl Chalcone (HMC) against the neurotoxicity induced by Aβ(25-35) peptide. HMC demonstrated higher free-radical scavenging activity than Hesperidin in initial cell-free studies. Investigations using the fluorescent dye thioflavin T with Aβ(25-35) peptide showed that HMC has the ability to combat extracellular amyloid aggregation by possessing anti-aggregation property against oligomers and by disaggregating mature fibrils. Also, the results of the molecular simulation studies show that HMC ameliorated oligomer formation. Further, the anti-Alzheimer's property of HMC was investigated in in vitro cell conditions by pre-treating the neuro 2a (N2a) cells with HMC before inducing Aβ(25-35) toxicity. The findings demonstrate that HMC increased cell viability, reduced oxidative stress, prevented macromolecular damage, allayed mitochondrial dysfunction, and exhibited anticholinesterase activity. HMC also reduced Aβ induced neuronal cell death by modulating caspase-3 activity, Bax expression and Bcl2 overexpression, demonstrating that HMC pre-treatment reduced mitochondrial damage and intrinsic apoptosis induced by Aβ(25-35). In silico evaluation against potential AD targets reveal that HMC could be a potent inhibitor of BACE-1, inhibiting the formation of toxic Aβ peptides. Overall, the findings imply that the neuroprotective efficacy of HMC has high prospects for addressing a variety of pathogenic consequences caused by amyloid beta in AD situations and alleviating cognitive impairments.
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