Laboratory of Genomics and Neurovascular Diseases, Universidad Católica de Santa María, Urb. San José s/n-Umacollo, Arequipa 04000, Peru.
Vicerrectorado de Investigación, Universidad Católica de Santa María, Urb. San José s/n-Umacollo, Arequipa 04000, Peru.
Molecules. 2022 Jan 28;27(3):918. doi: 10.3390/molecules27030918.
Despite research on the molecular bases of Alzheimer's disease (AD), effective therapies against its progression are still needed. Recent studies have shown direct links between AD progression and neurovascular dysfunction, highlighting it as a potential target for new therapeutics development. In this work, we screened and evaluated the inhibitory effect of natural compounds from native Peruvian plants against tau protein, amyloid beta, and angiotensin II type 1 receptor (AT1R) pathologic AD markers.
We applied in silico analysis, such as virtual screening, molecular docking, molecular dynamics simulation (MD), and MM/GBSA estimation, to identify metabolites from Peruvian plants with inhibitory properties, and compared them to nicotinamide, telmisartan, and grapeseed extract drugs in clinical trials.
Our results demonstrated the increased bioactivity of three plants' metabolites against tau protein, amyloid beta, and AT1R. The MD simulations indicated the stability of the AT1R:floribundic acid, amyloid beta:rutin, and tau:brassicasterol systems. A polypharmaceutical potential was observed for rutin due to its high affinity to AT1R, amyloid beta, and tau. The metabolite floribundic acid showed bioactivity against the AT1R and tau, and the metabolite brassicasterol showed bioactivity against the amyloid beta and tau.
This study has identified molecules from native Peruvian plants that have the potential to bind three pathologic markers of AD.
尽管针对阿尔茨海默病（AD）的分子基础已经进行了研究，但仍需要有效的进展抑制剂。最近的研究表明 AD 进展与神经血管功能障碍之间存在直接联系，这凸显了它作为新治疗药物开发的潜在靶标。在这项工作中，我们筛选和评估了来自秘鲁本土植物的天然化合物对 Tau 蛋白、淀粉样β蛋白和血管紧张素 II 型 1 受体（AT1R）病理性 AD 标志物的抑制作用。
我们应用了计算分析，如虚拟筛选、分子对接、分子动力学模拟（MD）和 MM/GBSA 估算，以鉴定具有抑制特性的秘鲁植物代谢产物，并将其与临床试验中的烟酰胺、替米沙坦和葡萄籽提取物药物进行了比较。
我们的结果表明，三种植物代谢产物对 Tau 蛋白、淀粉样β蛋白和 AT1R 的生物活性增加。MD 模拟表明 AT1R：floribundic 酸、淀粉样β：芦丁和 Tau：brassicasterol 系统的稳定性。芦丁由于其与 AT1R、淀粉样β蛋白和 Tau 的高亲和力，表现出多药治疗的潜力。代谢产物 floribundic 酸对 AT1R 和 Tau 具有生物活性，代谢产物 brassicasterol 对淀粉样β蛋白和 Tau 具有生物活性。
这项研究从秘鲁本土植物中鉴定出了一些可能与 AD 的三种病理标志物结合的分子。
