基于整合药理学平台的杜仲植物雌激素类成分治疗AD的作用机制研究
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摘要
目的从网络药理学角度探讨杜仲植物雌激素类成分治疗阿尔茨海默病的作用靶点及作用机制。方法基于文献和数据库检索获取杜仲植物雌激素类成分,以TTD治疗靶点数据库聚焦已证实的与阿尔茨海默病相关的直接靶标。最后通过Cytoscape及DAVID功能注释生物信息学分析关键代谢通路及代谢酶。结果通过类药五原则筛选获取白桦脂醇、黄芩素、染料木黄酮3个植物雌激素类成分。作用于50个体内靶点,其中核心靶点6个。这些靶点通过帕金森病等通路直接与疾病相关。结论本研究从网络药理学角度揭示了杜仲所含的植物雌激素类成分,发现直接涉及阿尔茨海默病相关的多个疾病靶标。这些靶点及通路为阐明杜仲植物雌激素类成分早期预防阿尔茨海默病作用提供了科学依据。
Objective To explore the target and mechanism of estrogen therapy for Alzheimer's disease in Eucommia from the perspective of network pharmacology. Methods Based on literature and database retrieval, the estrogen components of Eucommia are obtained. The TTD target database is used to focus on the confirmed targets associated with Alzheimer's disease. Finally, Cytoscape software is employed to visualize the above content and mechanism. Results A total of three main phytoestrogens of betulinol, baicalein, genistein are obtained by Lipinski's Rule of Five. A total of 50 targets are involved in the target, and there are 6 core targets. These targets are directly associated with Alzheimer's disease through Parkinson's disease. Conclusion The present investigation prove the phytoestrogen components of Eucommia with the perspective of network pharmacology, and found that it is directly related to the target directly associated with Alzheimer's disease. These targets and pathways provide a scientific basis for clarifying the early prevention of Alzheimer's disease phytoestrogens compounds from Eucommia.
Objective To explore the target and mechanism of estrogen therapy for Alzheimer's disease in Eucommia from the perspective of network pharmacology. Methods Based on literature and database retrieval, the estrogen components of Eucommia are obtained. The TTD target database is used to focus on the confirmed targets associated with Alzheimer's disease. Finally, Cytoscape software is employed to visualize the above content and mechanism. Results A total of three main phytoestrogens of betulinol, baicalein, genistein are obtained by Lipinski's Rule of Five. A total of 50 targets are involved in the target, and there are 6 core targets. These targets are directly associated with Alzheimer's disease through Parkinson's disease. Conclusion The present investigation prove the phytoestrogen components of Eucommia with the perspective of network pharmacology, and found that it is directly related to the target directly associated with Alzheimer's disease. These targets and pathways provide a scientific basis for clarifying the early prevention of Alzheimer's disease phytoestrogens compounds from Eucommia.
引文
[1]袁天翊,方莲花,吕扬,等.杜仲叶的药理作用研究进展[J].中国中药杂志, 2013, 38(6):781-785.
[2]王志宏,彭胜,雷明盛,等.杜仲主要生物活性研究进展[J].天然产物研究与开发, 2013, 25(9):1302-1309.
[3]林杰,江汉美,卢金清.HS-SPME-GC-MS法分析杜仲和杜仲叶中挥发性成分[J].安徽农业科学, 2018, 46(10):165-166+199.
[4]王金国,牟莹,房经武,等.杜仲补肾健骨颗粒对骨折不愈合患者血清标志物和血液流变学的影响[J].世界中医药, 2018, 13(2):333-336.
[5]刘跃辉,张波,李伟,等.杜仲叶醇提取物对去卵巢骨质疏松大鼠骨代谢生化指标、骨密度、IL-6及TNF-α的影响[J].中医学报,2018, 33(3):445-448.
[6]胡倩影,尹瑞林,王一飞,等.杜仲中松脂素二葡萄糖苷和松脂素对成骨细胞中OPG和RANKL表达的影响[J].中国实验方剂学杂志, 2018,24(10):181-186.
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[8]吴林霖,李梅,巩仔鹏,等.基于大鼠离体外翻肠囊模型考察杜仲提取物在正常和自发性高血压状态下的肠吸收特性差异[J].中国实验方剂学杂志, 2018, 24(9):15-21.
[9]Kwon S H, Lee H K, Kim J A, et al. Neuroprotective effects of Eucommia ulmoides Oliv. Bark on amyloid beta(25-35)-induced learning and memory impairments in mice[J]. Neuroscience Letters, 2011, 487(1):123-127.
[10] Seung-Hwan K, Ma S X, Hyun-Joong J, et al. Inhibitory Effects of Eucommiaulmoides Oliv. Bark on Scopolamine-Induced Learning and Memory Deficits in Mice[J]. Biomolecules&Therapeutics, 2013, 21(6):462-9.
[11]邹海曼.杜仲和补骨脂中活性植物雌激素成分对ESF-1细胞抗衰老基因调控机制的研究[D].哈尔滨:黑龙江中医药大学, 2013.
[12]尹昭晔.杜仲的植物雌激素活性成分研究[D].天津:天津大学, 2010.
[13] Klein J. Membrane breakdown in acute and chronic neurodegeneration:focus on choline-containing phospholipids[J]. Neural Transm, 2000,107:1027-1063.
[2]王志宏,彭胜,雷明盛,等.杜仲主要生物活性研究进展[J].天然产物研究与开发, 2013, 25(9):1302-1309.
[3]林杰,江汉美,卢金清.HS-SPME-GC-MS法分析杜仲和杜仲叶中挥发性成分[J].安徽农业科学, 2018, 46(10):165-166+199.
[4]王金国,牟莹,房经武,等.杜仲补肾健骨颗粒对骨折不愈合患者血清标志物和血液流变学的影响[J].世界中医药, 2018, 13(2):333-336.
[5]刘跃辉,张波,李伟,等.杜仲叶醇提取物对去卵巢骨质疏松大鼠骨代谢生化指标、骨密度、IL-6及TNF-α的影响[J].中医学报,2018, 33(3):445-448.
[6]胡倩影,尹瑞林,王一飞,等.杜仲中松脂素二葡萄糖苷和松脂素对成骨细胞中OPG和RANKL表达的影响[J].中国实验方剂学杂志, 2018,24(10):181-186.
[7]袁真,闵珺,王恺,等.杜仲黄酮类3种药物成分治疗大鼠骨质疏松的比较研究[J].中国骨质疏松杂志, 2018, 24(2):244-248.
[8]吴林霖,李梅,巩仔鹏,等.基于大鼠离体外翻肠囊模型考察杜仲提取物在正常和自发性高血压状态下的肠吸收特性差异[J].中国实验方剂学杂志, 2018, 24(9):15-21.
[9]Kwon S H, Lee H K, Kim J A, et al. Neuroprotective effects of Eucommia ulmoides Oliv. Bark on amyloid beta(25-35)-induced learning and memory impairments in mice[J]. Neuroscience Letters, 2011, 487(1):123-127.
[10] Seung-Hwan K, Ma S X, Hyun-Joong J, et al. Inhibitory Effects of Eucommiaulmoides Oliv. Bark on Scopolamine-Induced Learning and Memory Deficits in Mice[J]. Biomolecules&Therapeutics, 2013, 21(6):462-9.
[11]邹海曼.杜仲和补骨脂中活性植物雌激素成分对ESF-1细胞抗衰老基因调控机制的研究[D].哈尔滨:黑龙江中医药大学, 2013.
[12]尹昭晔.杜仲的植物雌激素活性成分研究[D].天津:天津大学, 2010.
[13] Klein J. Membrane breakdown in acute and chronic neurodegeneration:focus on choline-containing phospholipids[J]. Neural Transm, 2000,107:1027-1063.