基于雌激素靶标的药食同源中药抗骨质疏松活性网络药理学初探
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摘要
药食同源中药以其广泛的生物活性和安全的可食性越来越受到人们的关注。如何快速筛选并明确其活性成分一直是科学研究的热点。以15种药食同源中药为对象,应用网络药理学的方法,在前期工作中确定的中药雌激素相关靶标的基础上,通过构建化学成分数据库,预测生物口服利用度,计算类药性,构建分子对接及化合物-靶标网络,筛选具有潜在抗骨质疏松活性的中药,明确其具有雌激素样作用的活性成分。结果表明,15种药食同源中药的1 502个化学成分中,共有12种药食同源中药的361个化学成分(24%)为活性成分。其中,336个活性成分可与11个中药雌激素样作用靶标相互作用。化合物-靶标网络进一步展现了这12种药食同源中药防治骨质疏松的潜在活性。其中,黑芝麻和枸杞的潜在活性成分与靶标作用最密切,青果、山楂、甘草、莲子活性成分与靶标高度连接,表明这些活性化合物在骨质疏松防治功能方面发挥了重要作用。本研究可为药食同源中药抗骨质疏松保健功能的认识及开发提供新方法和理论依据。
The edible traditional Chinese medicine is becoming more and more high-profile owing to its extensive biological activity and credible edibility. However, it has been a hotspot of research that how to prescreen and identify active ingredients among the complicated traditional Chinese medicine systems. In this study, 15 edible traditional Chinese medicine were taken as study objects, basing on certain targets of estrogen-like action of traditional Chinese medicine in our previous work, and network pharmacology was established to investigate the anti-osteoporosis activity of15 medicine and screen active ingredients which have estrogen-like effect by integrating database construction, oral bioavailability screening, drug-likeness calculation, molecular docking analysis and compound-target network construction.The results indicated that total of 361 compounds(24%) of 12 edible traditional Chinese medicine were selected from1 502 compounds of 15 edible traditional Chinese medicine as the active components. Among of them, 336 active components are associated with 11 targets of estrogen-like action of Epimedium by using molecular docking. The compoundtarget network further displayed 12 edible traditional Chinese medicine have potential anti-osteoporosis activity. And some potential active components of Semen Sesami Nigrum and Lycium Chinense Miller were most closely related with associative targets, active ingredients of Fructus Canarii, Crataegus Pinnatifida Bge, Glycyrrhiza Uralensis Fisch. and Semen Nelumbinis had a high degree of attachment with related targets, explicating these potential active components play a major role in anti-osteoporosis. This study provided a novel method and theoretical basis for exploring hygienical function of anti-osteoporosis of edible traditional Chinese medicine.
The edible traditional Chinese medicine is becoming more and more high-profile owing to its extensive biological activity and credible edibility. However, it has been a hotspot of research that how to prescreen and identify active ingredients among the complicated traditional Chinese medicine systems. In this study, 15 edible traditional Chinese medicine were taken as study objects, basing on certain targets of estrogen-like action of traditional Chinese medicine in our previous work, and network pharmacology was established to investigate the anti-osteoporosis activity of15 medicine and screen active ingredients which have estrogen-like effect by integrating database construction, oral bioavailability screening, drug-likeness calculation, molecular docking analysis and compound-target network construction.The results indicated that total of 361 compounds(24%) of 12 edible traditional Chinese medicine were selected from1 502 compounds of 15 edible traditional Chinese medicine as the active components. Among of them, 336 active components are associated with 11 targets of estrogen-like action of Epimedium by using molecular docking. The compoundtarget network further displayed 12 edible traditional Chinese medicine have potential anti-osteoporosis activity. And some potential active components of Semen Sesami Nigrum and Lycium Chinense Miller were most closely related with associative targets, active ingredients of Fructus Canarii, Crataegus Pinnatifida Bge, Glycyrrhiza Uralensis Fisch. and Semen Nelumbinis had a high degree of attachment with related targets, explicating these potential active components play a major role in anti-osteoporosis. This study provided a novel method and theoretical basis for exploring hygienical function of anti-osteoporosis of edible traditional Chinese medicine.
引文
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[21]XU F F,DING Y,GUO Y Y,et al.Anti-osteoporosis effect of Epimedium via an estrogen-like mechanism based on a system-level[J].Journal of Ethnopharmacology,2016,177:148-160.
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[23]ZHENG C,WANG J,LIU J,et al.System-level multi-target drug discovery from natural products with applications to cardiovascular diseases[J].Molecular Diversity,2014,18(3):621-635.
[24]王守宝.壮骨汤治疗老年骨质疏松性胸腰椎压缩性骨折的临床研究[D].福州:福建中医药大学,2010.
[25]朱彩平,张声华.枸杞多糖对高脂血症小鼠血脂及脂质过氧化的影响[J].营养学报,2005,27(1):79-80.
[26]涂人顺,刘丽.黑芝麻和桃仁治疗老年性骨质疏松症的临床观察[C]//中华医学会第一次全国骨质疏松学术会议论文汇编.北京:中华医学会,2002:239-240.
[27]胡娅.补肾化痰方对绝经后骨质疏松症模型大鼠骨吸收的影响[D].武汉:湖北中医药大学,2011.
[28]李明慧,王桂敏.甘草附子汤对去卵巢大鼠骨组织中I型胶原代谢及组织蛋白酶K表达的影响[J].中国生化药物,2011,32(5):356-359.
[2]DAROSZEWSKA A.Prevention and treatment of osteoporosis in women:an update[J].Obstetrics Gynaecology and Reproductive Medicine,2015,25(7):181-187.
[3]NGUYE T V,CENTER J R,EISMAN J A.Association between breast cancer and bone mineral density:the dubbo osteporosis epidemiology study[J].Maturitas,2000,36(1):27-34.
[4]LI W F,HOU S X,YU B,et al.Genetics of osteoporosis:accelerating pace in gene identification and validation[J].Human Genetics,2010,127(3):249-285.
[5]ZHAO X L,FENG Y X,PENG Y.Prevention and treatment of osteoporosis with Chinese herbal medicines[J].Chinese Herbal Medicines,2012,4(4):265-270.
[6]CHEN K M,GE B H,ZHENG R L,et al.The serum of rats administered flavonoid extract from Epimedium sagittatum but not the extract itself enhances the development of rat calvarial osteoblast-like cells in vitro[J].Die Pharmazie,2004,59(1):61-64.
[7]JIA M,NIE Y,CAO D P,et al.Potential antiosteoporotic agents from plants:a comprehensive review[J].EvidenceBased Complementary and Alternative Medicine,2012,2012(4):277-293.
[8]RAJAGOPAL P L,AMRUTHA C,PREMALETHA K,et al.Medicinal plants in osteoporosis-a review[J].International Journal of Advances in Pharmacy,Biology and Chemistry,2013,2(4):605-608.
[9]吴丽,潘苏华.中药保健食品的优势及发展方向[J].时珍国医国药,2009,20(7):1838-1840.
[10]朱迪娜,王磊,王思彤,等.植物雌激素的研究进展[J].中草药,2012,43(7):1422-1429.
[11]杨林,孙静,郝璐.六味地黄丸组方的临床应用及研究[J].浙江中医药大学学报,2010,34(5):796-798.
[12]周奇,陈威妮,姜淼,等.利用文本挖掘技术探索中西医治疗骨质疏松症的用药规律[J].世界科学技术:中医药现代化,2012,14(1):1288-1293.
[13]陈韶坤,谢芳,张洪.中医药治疗原发性骨质疏松的研究进展[J].河南中医,2005,25(2):79-81.
[14]王新,方楚权,林远芳,等.芪藿丹健骨方治疗绝经后骨质疏松症50例疗效观察[J].新中医,2006,38(5):22-23.
[15]郭杨,马勇.中医药治疗骨质疏松症的常用处方分析[J].中国实验方剂学杂志,2010,16(7):188-191.
[16]RU J L,LI P,WANG J N,et al.TCMSP:a database of systems pharmacology for drug discovery from herbal medicines[J].Journal of Cheminformatics,2014,6(1):13-18.
[17]XU X,ZHANG W X,HUANG C,et al.A novel chemometric method for the prediction of human oral bioavailability[J].International Journal of Molecular Sciences,2012,13(6):6964-6982.
[18]VISTOLI G,PEDRETTI A,TESTA B.Assessing drug-likeness-what are we missing?[J].Drug Discovery Today,2008,13(7):285-294.
[19]TAO W Y,XU X,WANG X,et al.Network pharmacology-based prediction of the active ingredients and potential targets of Chinese herbal Radix Curcumae formula for application to cardiovascular disease[J].Journal of Ethnopharmacology,2013,145(1):1-10.
[20]WANG X,XU X,TAO W Y,et al.A systems biology approach to uncovering pharmacological synergy in herbal medicines with applications to cardiovascular disease[J].Evidence-Based Complementary and Alternative Medicine,2012,2012(6):1325-1339.
[21]XU F F,DING Y,GUO Y Y,et al.Anti-osteoporosis effect of Epimedium via an estrogen-like mechanism based on a system-level[J].Journal of Ethnopharmacology,2016,177:148-160.
[22]HUANG C,ZHENG C L,LI Y,et al.Systems pharmacology in drug discovery and therapeutic insight for herbal medicines[J].Briefings in Bioinformatics,2014,15(5):bbt035.
[23]ZHENG C,WANG J,LIU J,et al.System-level multi-target drug discovery from natural products with applications to cardiovascular diseases[J].Molecular Diversity,2014,18(3):621-635.
[24]王守宝.壮骨汤治疗老年骨质疏松性胸腰椎压缩性骨折的临床研究[D].福州:福建中医药大学,2010.
[25]朱彩平,张声华.枸杞多糖对高脂血症小鼠血脂及脂质过氧化的影响[J].营养学报,2005,27(1):79-80.
[26]涂人顺,刘丽.黑芝麻和桃仁治疗老年性骨质疏松症的临床观察[C]//中华医学会第一次全国骨质疏松学术会议论文汇编.北京:中华医学会,2002:239-240.
[27]胡娅.补肾化痰方对绝经后骨质疏松症模型大鼠骨吸收的影响[D].武汉:湖北中医药大学,2011.
[28]李明慧,王桂敏.甘草附子汤对去卵巢大鼠骨组织中I型胶原代谢及组织蛋白酶K表达的影响[J].中国生化药物,2011,32(5):356-359.