Tallini Luciana R, da Silva Camila Rockenbach, Jung Tatiana, Alves Elen de Oliveira, Baldin Samira Leila, Apel Miriam, Timmers Luis F S M, Rico Eduardo Pacheco, Bastida Jaume, Zuanazzi José Angelo S
Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, RS, Brazil.
Grup de Productes Naturals, Departament de Biologia, Sanitat i Medi Ambient, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, 08028 Barcelona, Spain.
Life (Basel). 2023 Aug 10;13(8):1721. doi: 10.3390/life13081721.
The Amaryllidaceae family constitutes an interesting source of exclusive alkaloids with a broad spectrum of biological activity. Galanthamine, the most relevant one, has been commercialized for the palliative treatment of Alzheimer's disease symptoms since 2001 due to its potential as an acetylcholinesterase (AChE) inhibitor. In vitro screenings against AChE by applying different Amaryllidaceae species and alkaloids have been reported in the literature; however, they are usually carried out using purified market enzymes. The main goal of this work is to evaluate the AChE inhibitory potential of (Amaryllidaceae) extracts using zebrafish brain homogenates. The biological assays show that the bulb extracts present an interesting AChE inhibitory activity in comparison with the positive reference control galanthamine (IC values of 1.20 ± 0.10 and 0.79 ± 0.15 μg/mL, respectively). The chemical profile of shows that this species has a high amount of galanthamine, which may contribute to the inhibitory effect on AChE activity of zebrafish brains. Computational experiments were used to build the model for zebrafish AChE and to evaluate the interactions between galanthamine and the enzymic active site. This work suggests that zebrafish could represent an important model in the search for bioactive molecules from the Amaryllidaceae family for the treatment of Alzheimer's disease.
石蒜科植物是具有广泛生物活性的独特生物碱的有趣来源。加兰他敏是其中最相关的一种，自2001年以来已商业化用于阿尔茨海默病症状的姑息治疗，因为它具有作为乙酰胆碱酯酶（AChE）抑制剂的潜力。文献中报道了通过应用不同的石蒜科植物物种和生物碱对AChE进行体外筛选；然而，这些筛选通常使用纯化的市售酶进行。这项工作的主要目标是使用斑马鱼脑匀浆评估石蒜科植物提取物的AChE抑制潜力。生物学测定表明，与阳性对照加兰他敏相比，石蒜科植物鳞茎提取物具有有趣的AChE抑制活性（IC值分别为1.20±0.10和0.79±0.15μg/mL）。石蒜科植物的化学特征表明，该物种含有大量加兰他敏，这可能有助于对斑马鱼脑AChE活性产生抑制作用。计算实验用于构建斑马鱼AChE模型，并评估加兰他敏与酶活性位点之间的相互作用。这项工作表明，斑马鱼可能是从石蒜科植物中寻找用于治疗阿尔茨海默病的生物活性分子的重要模型。
