The in silico and in vivo evaluation of puerarin against Alzheimer's disease
The in silico and in vivo evaluation of puerarin against Alzheimer's disease
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葛根素抗阿尔茨海默病的计算机和体内评价
DOI：
10.1039/c8fo01696h
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发表时间：
2019-02-01
期刊：
影响因子：
6.1
通讯作者：
Ma, Bing-Xin
中科院分区：
文献类型：
--
作者：
Liu, Song;Cao, Xiao-Lu;Ma, Bing-Xin
在中国，葛根的根被用作食物来源已有数千年的历史。葛根素是从葛根中提取的主要生物活性物质和最丰富的次生代谢产物。通过计算机方法筛选葛根素对阿尔茨海默病的潜在治疗作用，并通过淀粉样肽诱导的阿尔茨海默病（AD）大鼠模型得到证实。计算机模拟研究表明，葛根素具有穿过血脑屏障的潜力，并且在与乙酰胆碱酯酶（AChE）、环氧合酶-2（COX-2）和半胱天冬酶-3（C3）的分子对接和动力学模拟中具有较高的稳定性，在AD的发生发展中发挥着核心作用。体内实验结果表明，葛根素可抑制AChE活性，使抗氧化防御物质的活性恢复至正常水平，并降低脑内炎症因子和凋亡基因的表达，特别是下调COX-2和C3的表达。脑切片的组织病理学检查和行为测试也验证了生化观察结果，这进一步验证了计算机研究。这些结果不仅表明葛根素作为一种潜在的化合物可以缓解AD，而且拓宽了葛根素的应用。
The root of Pueraria lobata has been utilized as a food source for thousands of years in China. Puerarin is the major bioactive and the most abundant secondary metabolite obtained from the root of P. lobata. The potential therapeutic effect of puerarin against Alzheimer's disease was screened by in silico methods and confirmed by the amyloid -peptide-induced Alzheimer's disease (AD) rat model. The in silico study displayed that puerarin had the potential to penetrate across the blood-brain barrier and had high stability in molecular docking and dynamics simulation with acetylcholinesterase (AChE), cyclooxygenase-2 (COX-2) and caspase-3 (C3), which play a central role in the development of AD. The in vivo results showed that puerarin could restrain the AChE activity, restore the activities of antioxidant defense substances toward normal levels, and decrease the expression of inflammatory factors and apoptosis genes in the brain, especially down-regulating the expressions of COX-2 and C3. The histopathological examination of brain sections and behavioral testing also verified the biochemical observations, which further validates the in silico study. These results not only suggest that puerarin, as a potential compound, could relieve AD, but also broaden the applications of puerarin.