背景:阿尔茨海默病(AD)是一种全球范围内普遍存在的神经系统疾病,影响数百万人,并对认知功能产生严重影响。淀粉样蛋白假说,将AD与Aβ(淀粉样蛋白β)斑块聚集联系起来,是一个公认的理论。β-分泌酶(BACE1)是Aβ产生的主要原因,这使得它成为可能的治疗目标。FDA批准的AD疗法确实存在,但它们均未明确靶向BACE1,其有效性受到限制并伴有不良反应.
方法:我们通过对BACE1进行全面的文献研究,确定了草药的基本化学成分。计算方法,如分子对接,ADMET(吸收,分布,新陈代谢,排泄,毒性)筛查,分子动力学模拟,进行MMPBSA分析以鉴定β-分泌酶的最有希望的配体。
结果:结果表明,Tinosporide,和姜黄素与BACE1具有更好的结合亲和力,表明它们有潜力作为治疗阿尔茨海默病的候选药物。
结论:草药疗法在治疗阿尔茨海默病等慢性疾病中具有巨大的应用,并且迫切需要评估其作为治疗剂的功效。
BACKGROUND: Alzheimer\'s disease (AD) is an alarmingly prevalent worldwide neurological disorder that affects millions of people and has severe effects on cognitive functions. The amyloid hypothesis, which links AD to Aβ (amyloid beta) plaque aggregation, is a well-acknowledged theory. The β-secretase (
BACE1) is the main cause of Aβ production, which makes it a possible target for therapy. FDA-approved therapies for AD do exist, but none of them explicitly target
BACE1, and their effectiveness is constrained and accompanied by adverse effects.
METHODS: We determined the essential chemical components of medicinal herbs by conducting a thorough literature research for
BACE1. Computational methods like molecular docking, ADMET (Absorption, distribution, metabolism, excretion, toxicity) screening, molecular dynamic simulations, and MMPBSA analysis were performed in order to identify the most promising ligands for β-secretase.
RESULTS: The results suggested that withasomniferol, tinosporide, and curcumin had better binding affinity with
BACE1, suggesting their potential as therapeutic candidates against Alzheimer\'s disease.
CONCLUSIONS: Herbal therapeutics have immense applications in the treatment of chronic diseases like Alzheimer\'s disease, and there is an urgent need to assess their efficacy as therapeutics.