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石蒜碱与加兰他敏与淀粉样蛋白 β 相互作用能力及体外神经毒性降低的比较研究。

A Comparative Study between Lycorine and Galantamine Abilities to Interact with AMYLOID β and Reduce In Vitro Neurotoxicity.

机构信息

Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.

CIRMMP, Via Luigi Sacconi 6, 50019 Firenze, Italy.

出版信息

Int J Mol Sci. 2023 Jan 28;24(3):2500. doi: 10.3390/ijms24032500.

Abstract

Galantamine is a natural alkaloid extracted from the plants and is used as the active ingredient of a drug approved for the treatment of the early stages of Alzheimer's disease. It mainly acts as an acetylcholinesterase (AChE) inhibitor, increasing concentrations of the acetylcholine neurotransmitter. Recent cellular studies have also shown the ability of galantamine to protect SH-SY5Y cell lines against amyloid-β (Aβ)-induced toxicity. Such investigations have supported and validated further in-depth studies for understanding the chemical and molecular features associated with galantamine-protective abilities. In addition to galantamine, other natural alkaloids are known to possess AChE inhibitory activity; among them lycorine has been extensively investigated for its antibacterial, anti-inflammatory and antitumoral activities as well. Despite its interesting biological properties, lycorine's neuroprotective functions against Aβ-induced damages have not been explored so far. In this research study, the ability of galantamine and lycorine to suppress Aβ-induced in vitro neuronal toxicity was evaluated by investigating the chemical interactions of the two alkaloids with Aβ peptide. A multi-technique spectroscopic analysis and cellular cytotoxicity assays were applied to obtain new insights on these molecular associations. The comparison between the behaviors exhibited by the two alkaloids indicates that both compounds possess analogue abilities to interact with the amyloidogenic peptide and protect cells.

摘要

加兰他敏是一种从植物中提取的天然生物碱,用作治疗阿尔茨海默病早期阶段的药物的活性成分。它主要作为乙酰胆碱酯酶 (AChE) 抑制剂,增加乙酰胆碱神经递质的浓度。最近的细胞研究还表明加兰他敏能够保护 SH-SY5Y 细胞系免受淀粉样蛋白-β (Aβ) 诱导的毒性。这些研究支持并进一步验证了对与加兰他敏保护能力相关的化学和分子特征的深入研究。除了加兰他敏,其他天然生物碱也被认为具有 AChE 抑制活性;其中石蒜碱因其抗菌、抗炎和抗肿瘤活性而得到广泛研究。尽管具有有趣的生物学特性,但石蒜碱对 Aβ 诱导损伤的神经保护作用迄今尚未得到探索。在这项研究中,通过研究两种生物碱与 Aβ 肽的化学相互作用,评估了加兰他敏和石蒜碱抑制体外神经元毒性的能力。应用多种光谱分析技术和细胞毒性测定法,对这些分子相关性进行了新的研究。两种生物碱表现出的行为之间的比较表明,这两种化合物都具有与淀粉样蛋白肽相互作用并保护细胞的类似能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea50/9916559/7a92bdc71eba/ijms-24-02500-g001.jpg

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