基于网络药理学方法探讨蛇床子治疗骨质疏松可能的分子途径
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摘要
目的采用网络药理学方法探讨蛇床子抗骨质疏松的可能分子途径。方法利用中药系统药理学数据库(TCMSP)筛选蛇床子活性成分,预测靶蛋白和相互作用蛋白;用TTD和CTD数据库查询骨质疏松靶蛋白,预测相互作用蛋白,构建药物–靶蛋白–疾病交互网络;用DAVID数据库富集并分析靶蛋白信号通路;通过Systems Dock软件将蛇床子活性成分与重要的靶蛋白进行分子对接验证。结果筛选得到蛇床子活性成分19个、靶蛋白72个、骨质疏松疾病靶蛋白118个;经相互作用蛋白(PPI)网络交集后,获得药物和疾病共同靶蛋白91个;富集得到26条信号通路;β-谷固醇、豆甾醇、24-epicampesterol、poriferast-5-en-3β-ol与SRC、ESR1靶蛋白具有良好的分子对接活性。结论蛇床子可能通过激活甲状腺激素信号通路中的SRC和ESR1起到治疗骨质疏松的作用。
Objective To explore the possible molecular mechanism of Cnidii fructus on anti-osteoporosis based on network pharmacology. Methods The active components of Cnidii fructus were screened by Traditional Chinese Medicine Systems Pharmacology Database(TCMSP)to predict the target proteins and interaction proteins.Osteoporosis target proteins were derived from CTD and TTD databases, and their interaction proteins were predicted. Then the drug-target protein-disease correlation network was constructed. The signal pathways of targeted proteins were enriched and analyzed with DAVID database. Molecular docking of the active ingredients of Cnidii fructus with important target proteins was verified by Systems Dock software. Results Nineteen active ingredients of Cnidii fructus and 72 target proteins were retrieved, 118 target proteins of osteoporosis were selected, and 91 common target proteins of Cnidii fructus and osteoporosis were obtained. Then 26 signaling pathways were enriched.High molecular docking scores between active components(β-Sitosterol, Stigmasterol, 24-epicampesterol and poriferast-5-en-3β-ol)and ESR1,SRC were obtained. Conclusion The results show that Cnidii fructus may play a key role in the treatment of osteoporosis by activating SRC and ESR1 in thyroid hormone signaling pathway.
Objective To explore the possible molecular mechanism of Cnidii fructus on anti-osteoporosis based on network pharmacology. Methods The active components of Cnidii fructus were screened by Traditional Chinese Medicine Systems Pharmacology Database(TCMSP)to predict the target proteins and interaction proteins.Osteoporosis target proteins were derived from CTD and TTD databases, and their interaction proteins were predicted. Then the drug-target protein-disease correlation network was constructed. The signal pathways of targeted proteins were enriched and analyzed with DAVID database. Molecular docking of the active ingredients of Cnidii fructus with important target proteins was verified by Systems Dock software. Results Nineteen active ingredients of Cnidii fructus and 72 target proteins were retrieved, 118 target proteins of osteoporosis were selected, and 91 common target proteins of Cnidii fructus and osteoporosis were obtained. Then 26 signaling pathways were enriched.High molecular docking scores between active components(β-Sitosterol, Stigmasterol, 24-epicampesterol and poriferast-5-en-3β-ol)and ESR1,SRC were obtained. Conclusion The results show that Cnidii fructus may play a key role in the treatment of osteoporosis by activating SRC and ESR1 in thyroid hormone signaling pathway.
引文
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[20]张善强,李永涛,孙石柱,等.神经营养因子-3通过Wnt通路促进人骨髓间充质干细胞生长和成骨分化的研究[J].中国现代医学杂志2016,26(15):6-10.
[21]王亮,刘安宁,王亚兰,等.甲状腺功能亢进患者骨密度和血清骨代谢指标的变化及相关性分析[J].临床荟萃2013,28(10):1141-1142.
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[2]CHENG M H,CHEN J F,FUH J L,et al.Osteoporosis treatment in postmenopausal women with preexisting fracture[J].Taiwanese Journal of Obstetrics and Gynecology,2012,51(2):153-166.
[3]FU J,HU S M,YANG J J,et al.Comparison between postmenopausal osteoporosis and weightlessness osteoporosis based on syndrome differentiation of TCM[J].Chinese Journal of Information on TCM,2009,5(16):1-2.
[4]CHEN H X,LI S L,CHEN W H.Investigation of the relationship between the disharmony between bone and muscle theory and osteoporosis[J].Chin J Osteoporos,2016,22(6):781-785,790.
[5]张耀武,陈平波,洪汉刚,等.中医补肾活血法对原发性骨质疏松症患者骨密度、骨代谢及脆性骨折发生率的影响[J].现代中西医结合杂志,2017,26(1):65-67.
[6]郑立卿,张力,董晓华,等.蛇床子素药理作用研究进展[J].神经药理学报,2013,3(6):29-35.
[7]马勇,汪志芳,王培民.自拟温肾通络止痛方治疗骨质疏松症45例临床研究[J].中医药学报,2010,38(1):103-104.
[8]郑苏扬,马勇,郭杨,等.“温肾通络止痛方”治疗原发性骨质疏松症的疗效观察及处方优化[J].辽宁中医杂志,2016,43(10):2098-2100.
[9]XUE R,FANG Z,ZHANG M,et al.TCMID:traditional Chinese medicine integrative database for herb molecular mechanism analysis[J].Nucleic Acids Res,2013,41:D1089-D1095.
[10]马勇,郭杨,袁涛,等.蛇床子素骨靶向药物对体外培养大鼠成骨细胞增殖功能的影响[J].中国骨质疏松杂志2012,18(9):781-784.
[11]王青,张云,毛红娇,等.蛇床子素对TCP颗粒诱导小鼠颅骨溶解的影响[J].中国病理生理杂志2015,1(12):2265-2270.
[12]明磊国,葛宝丰,陈克明,等.蛇床子素对体外培养骨髓基质干细胞增殖与成骨性分化的影响[J].中国药理学通报2010,26(8):1098-1103.
[13]吴芳,刘新宇,陈连剑,等.蛇床子总香豆素的测定及其提取条件的正交设计优选[J].中药新药与临床药理,2002(2):113-116,134.
[14]沃小敏,伍冠一,王海霞.蛇床子防治骨质疏松的研究概况[J].中国民族民间医药,2018,27(20):34-38.
[15]陈亚辉,龚忠勤,崔燎.PI3K/Akt信号通路在骨质疏松病理过程中的作用[J].中国骨质疏松杂志2015,21(3):356-360.
[16]张波,耿彬,谭小义,等.MAPK信号通路与骨质疏松关系的研究进展[J].中国矫形外科杂志2014,22(23):2161-2164.
[17]王小娜,李正,王暘,等.TGF-β1在雷奈酸锶促进大鼠骨髓间充质干细胞向成骨细胞分化中的作用[J].中国病理生理杂志2011,27(12):2357-2361.
[18]FAN J Z,YANG L,MENG G L,et al.Estrogen improves the proliferation and differentiation of h BMSCs derived from postmenopausal osteoporosis through notch signaling pathway[J].Mol Cell Biochem,2014,392(1-2):85-93.
[19]HE S,SHEN L,WU Y,et al.Effect of brain-derived neurotrophic factor on mesenchymal stem cell-seeded electrospinning biomaterial for treating ischemic diabetic ulcers via milieu-dependent differentiation mechanism[J].Tissue Eng Part A,2015,21(5-6):928-938.
[20]张善强,李永涛,孙石柱,等.神经营养因子-3通过Wnt通路促进人骨髓间充质干细胞生长和成骨分化的研究[J].中国现代医学杂志2016,26(15):6-10.
[21]王亮,刘安宁,王亚兰,等.甲状腺功能亢进患者骨密度和血清骨代谢指标的变化及相关性分析[J].临床荟萃2013,28(10):1141-1142.
[22]ONIGATA K.Hormones and cytokines in bone metabolism.Thyroid hormone and skeletal metabolism[J].Clinn Calcium,2014,24(6):821-827.
[23]王艳,杨维.甲状腺功能减退症与骨代谢的相关性研究[J].河南医学研究,2015,(8):16-19.
[24]MARTIN-MILLAN M,ALMEIDA M,AMBROGINI E,et al.The estrogen receptor-alpha in osteoclasts mediates the protective effects of estrogens on cancellous but not cortical bone[J].Mol Endocrinol,2010,24(2):323-334.
[25]PENG X D,XU P Z,CHEN M L,et al.Dwarfism,impaired skin development,skeletal muscle atrophy,delayed bone development,and impeded adipogenesis in mice lacking Akt1 and Akt2[J].Genes Dev,2003,17(11):1352-1365.