School of Pharmacy, Department of Pharmacology, Anurag University, Hyderabad, Telangana, India.
Department of Pharmacognosy & Phyto-Pharmacy, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Nilgiris, Tamil Nadu, India.
Adv Exp Med Biol. 2023;1423:237-243. doi: 10.1007/978-3-031-31978-5_23.
Vascular dementia (VaD) accounts to 30% of cases and is predicted as second most common form of dementia after Alzheimer's disease by WHO. Earlier studies reported that plant-derived pentacyclic triterpenoids possess a wide range of pharmacological activities but these compounds are not extensively studied for their neuroprotective potential against VaD. This in silico approach was designed to screen 20 pentacyclic triterpenoid plant compounds against known targets of VaD using Flare software. S-Adenyl homocysteine hydrolase, Acetylcholinesterase, and Butyrylcholinesterase were selected as important VaD targets, and various parameters like intermolecular interaction energies, binding energy, and dock scores were analyzed and compared between selected ligands. Our results showed that Ursolic acid has lowest binding energy when docked with most of the target proteins, and among all 20 pentacyclic triterpenoids studied, only three ligands Betulinic acid, Ambolic acid, and Madecassic acid, showed better binding energy scores, and they can be shortlisted as lead compounds to further study their therapeutic potential against VaD using in vitro and in vivo animal models.
血管性痴呆（VaD）占 30%，世界卫生组织预测它是仅次于阿尔茨海默病的第二大常见痴呆症类型。早期研究表明，植物来源的五环三萜类化合物具有广泛的药理活性，但这些化合物的神经保护潜力针对 VaD 的研究并不广泛。本研究采用 Flare 软件，通过计算机模拟筛选了 20 种五环三萜植物化合物针对 VaD 的已知靶点。S-腺苷同型半胱氨酸水解酶、乙酰胆碱酯酶和丁酰胆碱酯酶被选为 VaD 的重要靶点，分析并比较了所选配体之间的分子间相互作用能、结合能和对接分数等各种参数。结果表明，乌苏酸与大多数靶蛋白结合时具有最低的结合能，在所研究的 20 种五环三萜中，只有三种配体白桦脂酸、阿朴酸和麦迪酸具有更好的结合能分数，它们可以被选为先导化合物，通过体外和体内动物模型进一步研究它们治疗 VaD 的潜力。
