Abstract:
Based on compelling experimental and clinical evidence, Ginkgo biloba L. exerts a beneficial effect in ameliorating mild to moderate dementia in patients with Alzheimer’s disease (AD) and other neurological disorders, although the pharmacological mechanisms remain unknown. In the present study, compounds, their putative target proteins identified using an inverse docking approach, and clinically tested AD-related target proteins were systematically integrated together with applicable bioinformatics methods in silico. The results suggested that the beneficial effects of G. biloba on AD may be contributed by the regulation of hormone sensitivity, improvements in endocrine homeostasis, maintenance of endothelial microvascular integrity, and proteolysis of tau proteins, particularly prior to amyloid β-protein (Aβ) plaque formation. Moreover, we identified six putative protein targets that are significantly related to AD, but have not been researched or have had only preliminary studies conducted on the anti-AD effects of G. biloba. These mechanisms and protein targets are very significant for future scientific research. In addition, the existing mechanisms were also verified, such as the reduction of oxidative stress, anti-apoptotic effects, and protective effects against amyloidogenesis and Aβ aggregation. The discoveries summarized here may provide a macroscopic perspective that will improve our understanding of the molecular mechanism of medicinal plants or dietary supplements, as well as new clues for the future development of therapeutic strategies for AD.
摘要:
基于令人信服的实验和临床证据,银杏对改善阿尔茨海默病(AD)和其他神经系统疾病患者的轻度至中度痴呆具有有益作用,虽然药理机制仍然未知。在本研究中,化合物,他们使用反向对接方法鉴定的推定靶蛋白,和临床测试的AD相关靶蛋白与适用的生物信息学方法在计算机上进行了系统的整合。结果表明,银杏叶对AD的有益作用可能与调节激素敏感性有关。改善内分泌稳态,维持内皮微血管完整性,和tau蛋白的蛋白水解,特别是在淀粉样蛋白和β;-蛋白(A&β;)斑块形成之前。此外,我们确定了六个与AD显著相关的蛋白质靶点,但尚未进行研究,或仅对银杏叶的抗AD作用进行了初步研究。这些机制和蛋白质靶标对未来的科学研究非常重要。此外,现有机制也得到了验证,例如减少氧化应激,抗凋亡作用,以及对淀粉样蛋白生成和A&β;聚集的保护作用。这里总结的发现可能提供了一个宏观的观点,这将提高我们对药用植物或膳食补充剂的分子机制的理解,以及未来发展AD治疗策略的新线索。