Anti-Alzheimer's Studies on β-Sitosterol Isolated from Polygonum hydropiper L.
Anti-Alzheimer's Studies on β-Sitosterol Isolated from Polygonum hydropiper L.
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DOI：
10.3389/fphar.2017.00697
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发表时间：
2017
影响因子：
5.6
通讯作者：
Ahmad S
中科院分区：
文献类型：
--
作者：
Ayaz M;Junaid M;Ullah F;Subhan F;Sadiq A;Ali G;Ovais M;Shahid M;Ahmad A;Wadood A;El-Shazly M;Ahmad N;Ahmad S
该科是已知的，其传统的使用在管理各种神经系统疾病，包括阿尔茨海默氏病（AD）。为了寻找新的抗阿尔茨海默病药物，对从辣蓼中分离得到的β-谷甾醇进行了体外、体内、行为学和分子对接研究，以证实其作为抗阿尔茨海默病药物的可能性。采用Ellman法研究了β-谷甾醇对乙酰胆碱酯酶（AChE）、乙酰胆碱酯酶（BChE）的体外抑制作用。采用DPPH法、ABTS法和H2 O2法测定其抗氧化活性。采用浅水迷宫、Y型迷宫和平衡木实验对转基因小鼠亚系进行行为学研究。测试β-谷甾醇对额叶皮层（FC）和海马（HC）中胆碱酯酶和自由基的体内抑制潜力。通过分子对接研究，预测了β-谷甾醇在AChE活性位点的结合方式，并预测了BChE作为抑制剂的作用方式。β-谷甾醇处理组在体外和体内均观察到相当大的胆碱酯酶抑制作用。β-谷甾醇对AChE和BChE的IC_（50）分别为55和50 μg/ml。而转基因动物的FC和HC匀浆中这些酶的活性显著降低。分子对接研究也支持β-谷甾醇与靶酶的结合，并进一步支持体外和体内结果。在抗氧化试验中，DPPH、ABTS和H2 O2试验中观察到的IC 50值分别为140、120和280 μg/ml。与转基因盐水处理组相比，β-谷甾醇处理组动物脑组织中的自由基负荷显著下降。在记忆评估和协调任务（包括SWM、Y-迷宫和平衡木测试）中，β-谷甾醇处理的转基因动物在工作记忆、自发交替行为和运动协调方面表现出逐渐改善。这些结果得出结论，β-谷甾醇是一种潜在的化合物，用于管理记忆缺陷疾病，如AD。
The family Polygonaceae is known for its traditional use in the management of various neurological disorders including Alzheimer’s disease (AD). In search of new anti-AD drugs, β-sitosterol isolated from Polygonum hydropiper was subjected to in vitro, in vivo, behavioral and molecular docking studies to confirm its possibility as a potential anti-Alzheimer’s agent. The in vitro AChE, BChE inhibitory potentials of β-sitosterol were investigated following Ellman’s assay. The antioxidant activity was tested using DPPH, ABTS and H2O2 assays. Behavioral studies were performed on a sub-strain of transgenic mice using shallow water maze (SWM), Y-maze and balance beam tests. β-sitosterol was tested for in vivo inhibitory potentials against cholinesterase’s and free radicals in the frontal cortex (FC) and hippocampus (HC). The molecular docking study was performed to predict the binding mode of β-sitosterol in the active sites of AChE and BChE as inhibitor. Considerable in vitro and in vivo cholinesterase inhibitory effects were observed in the β-sitosterol treated groups. β-sitosterol exhibited an IC50 value of 55 and 50 μg/ml against AChE and BChE respectively. Whereas, the activity of these enzymes were significantly low in FC and HC homogenates of transgenic animals. Molecular docking studies also support the binding of β-sitosterol with the target enzyme and further support the in vitro and in vivo results. In the antioxidant assays, the IC50 values were observed as 140, 120, and 280 μg/ml in the DPPH, ABTS and H2O2 assays respectively. The free radicals load in the brain tissues was significantly declined in the β-sitosterol treated animals as compared to the transgenic-saline treated groups. In the memory assessment and coordination tasks including SWM, Y-maze and balance beam tests, β-sitosterol treated transgenic animals showed gradual improvement in working memory, spontaneous alternation behavior and motor coordination. These results conclude that β-sitosterol is a potential compound for the management of memory deficit disorders like AD.
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影响因子：
5.8
作者：
ELLMAN, GL;COURTNEY, KD;FEATHERSTONE, RM
通讯作者：
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影响因子：
5.5
作者：
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