Post-Graduation Program of Food Technology (PPGTA), Federal University of Technology - Paraná - UTFPR, Brazil; Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, Bragança, Portugal.
Post-Graduation Program of Food Technology (PPGTA), Federal University of Technology - Paraná - UTFPR, Brazil.
Food Res Int. 2023 Nov;173(Pt 1):113295. doi: 10.1016/j.foodres.2023.113295. Epub 2023 Jul 20.
Researchers have concentrated efforts in the search for natural-based reversible inhibitors for cholinesterase enzymes as they may play a key role in the treatment of degenerative diseases. Diverse plant alkaloids can inhibit the action of acetylcholinesterase and, among them, berberine is a promising bioactive. However, berberine has poor water solubility and low bioavailability, which makes it difficult to use in treatment. The solid dispersion technique can improve the water affinity of hydrophobic substances, but berberine solid dispersions have not been extensively studied. Safety testing is also essential to ensure that the berberine-loaded solid dispersions are safe for use. This study investigated the effectiveness of berberine-loaded solid dispersions (SD) as inhibitors of acetylcholinesterase enzyme (AChE). Docking simulation was used to investigate the influence of berberine on AChE, and in vitro assays were conducted to confirm the enzymatic kinetics of AChE in the presence of berberine. Berberine SD also showed improved cytotoxic effects on tumoral cells when dispersed in aqueous media. In vivo assays using Allium cepa were implemented, and no cytotoxicity/genotoxicity was found for the berberine solid dispersion. These results suggest that berberine SD could be a significant step towards safe nanostructures for use in the treatment of neurodegenerative diseases.
研究人员一直致力于寻找基于天然的、可逆转的乙酰胆碱酯酶抑制剂，因为它们可能在退行性疾病的治疗中发挥关键作用。许多植物生物碱可以抑制乙酰胆碱酯酶的作用，其中，小檗碱是一种很有前途的生物活性物质。然而，小檗碱的水溶性差，生物利用度低，这使得它很难用于治疗。固体分散技术可以提高疏水性物质的亲水性，但小檗碱固体分散体尚未得到广泛研究。安全性测试也是必不可少的，以确保载有小檗碱的固体分散体的使用是安全的。本研究探讨了载有小檗碱的固体分散体（SD）作为乙酰胆碱酯酶（AChE）抑制剂的效果。通过对接模拟研究了小檗碱对 AChE 的影响，并进行了体外试验以确认 AChE 在存在小檗碱时的酶动力学。当在水性介质中分散时，小檗碱 SD 还显示出对肿瘤细胞的改善的细胞毒性作用。使用洋葱实施了体内试验，未发现小檗碱固体分散体的细胞毒性/遗传毒性。这些结果表明，小檗碱 SD 可能是朝着用于治疗神经退行性疾病的安全纳米结构迈出的重要一步。
