基于网络药理学的骨碎补“疗伤止痛,补肾强骨”作用机制初探
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摘要
目的:从分子信息层面分析中药骨碎补药效的物质基础和作用机制,进而对其可能具有的未知疗效进行初步预测。方法:运用系统药理学研究方法,从中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacolo)中检索出与骨碎补相关的所有化学成分,设定口服利用度(OB)≥50%和类药性(DL)≥0.18为高活性化合物分子的筛选条件。通过中药系统药理学数据库与分析平台(TCMSP)寻找与所得化合物相关的潜在靶点以及与靶点相关的所有疾病,进而构建化合物-靶点、靶点-疾病相互作用网络图并进行统计分析。结果:筛选得到7个候选活性分子,相应靶点有56个,相关疾病有131种。化合物按度值降序排列依次为naringenin、Aureusidin、(+)-catechin、eriodictyol、davallioside A_qt、digallate、marioside_qt;度值较高的潜在靶标为Prostaglandin G/H synthase 2、DNA topoisomerase II、Heat shock protein HSP 90等;度值较高的相关疾病为乳腺癌、前列腺癌、炎症疾病、神经退行性疾病、骨质疏松等。结论:本研究初步验证了骨碎补"疗伤止痛,补肾强骨"的功效,为挖掘骨碎补的临床应用及深入研究其作用机制奠定了基础。
Objective: To analyze the material basis and mechanism of Chinese medicine Osteopractic efficacy from biological molecules and discuss its unknown effects. Methods: The methods of systems pharmacology are used.First, all chemicals and related Osteopractic targets on Traditional Chinese Medicine Systems Pharmacolo were retrieved by setting the oral bioavailability(OB)≥50% and drug likeness(DL) ≥0.18 screening conditions for high activity compound. Through analysis of traditional Chinese medicine and pharmacology database platform system(TCMSP) to find potential targets associated with the compounds and targets of all diseases related to the statistical analysis so as to construct the compound-target network and target-disease network. Results: Through the screening of OB and DL, 7 candidate molecules were obtained. There were 56 corresponding targets and 131 related diseases. According to the value of the rank of the candidate compounds were naringenin, Aureusidin,(+)-catechin, eriodictyol, davallioside A_qt, digallate, marioside_qt; values of potential targets were higher for Prostaglandin synthase 2 G/H, DNA topoisomerase II, Heat shock protein HSP 90; degree of diseases related to higher breast cancer and prostate cancer, inflammatory diseases, neurodegenerative diseases, osteoporosis etc. Conclusion: This study validated the "healing wounds, relieving pain, tonifying the kidney and strengthening bones", which laid a good foundation for the comprehensive mining Osteopractic clinical application and in-depth study of its mechanism.
Objective: To analyze the material basis and mechanism of Chinese medicine Osteopractic efficacy from biological molecules and discuss its unknown effects. Methods: The methods of systems pharmacology are used.First, all chemicals and related Osteopractic targets on Traditional Chinese Medicine Systems Pharmacolo were retrieved by setting the oral bioavailability(OB)≥50% and drug likeness(DL) ≥0.18 screening conditions for high activity compound. Through analysis of traditional Chinese medicine and pharmacology database platform system(TCMSP) to find potential targets associated with the compounds and targets of all diseases related to the statistical analysis so as to construct the compound-target network and target-disease network. Results: Through the screening of OB and DL, 7 candidate molecules were obtained. There were 56 corresponding targets and 131 related diseases. According to the value of the rank of the candidate compounds were naringenin, Aureusidin,(+)-catechin, eriodictyol, davallioside A_qt, digallate, marioside_qt; values of potential targets were higher for Prostaglandin synthase 2 G/H, DNA topoisomerase II, Heat shock protein HSP 90; degree of diseases related to higher breast cancer and prostate cancer, inflammatory diseases, neurodegenerative diseases, osteoporosis etc. Conclusion: This study validated the "healing wounds, relieving pain, tonifying the kidney and strengthening bones", which laid a good foundation for the comprehensive mining Osteopractic clinical application and in-depth study of its mechanism.
引文
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[10] 翟远坤, 潘亚磊, 牛银波,等. 柚皮苷及其代谢物柚皮素对乳鼠颅骨成骨细胞分化成熟影响的比较研究[J]. 中国药学杂志, 2013, 48(16):1373-1379.
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[12] 吴新涛, 石晶, 高乐才,等. 柚皮素对氧化应激所致成骨细胞凋亡的影响及机制研究[J]. 河北医药, 2016, 38(19):2915-2918.
[13] 张亦凡, 刘功关, 刘茜,等. 圣草酚抑制自由基诱导的生物大分子损伤及对肝癌细胞HepG2毒性的作用[J]. 食品科学, 2013, 34(17):126-130.
[14] SONG F, ZHOU L, ZHAO J, et al. Eriodictyol Inhibits RANKL-Induced Osteoclast Formation and Function via Inhibition of NFATc1 Activity[J]. Journal of Cellular Physiology, 2016, 231(9):1983.
[15] LI L, ZENG Z, CAI G. Comparison of neoeriocitrin and naringin on proliferation and osteogenic differentiation in MC3T3-E1[J]. Phytomedicine, 2011, 18(11):985-989.
[16] 徐永跃, 黄清春, 何羿婷,等. COX-2/TxA_2通路在炎症相关疾病中的分子机制研究进展[J]. 中国中西医结合杂志, 2017, 37(6):763-767.
[17] 李洋, 陈前昭, 邵英,等. 骨形态蛋白9诱导干细胞骨向分化与环氧酶-2及PI3K/Akt的关系研究[J]. 中国药理学通报, 2017, 33(7):908-915.
[18] 郭晓华, 李俊萍, 张昕.阿托伐他汀通过促进热休克蛋白90表达减少急诊经皮冠状动脉介入治疗术后对比剂肾病的发生率[J].中国循环杂志, 2015, 30(9):845-48.
[19] 李润玖, 李锐, 张彧. 热休克蛋白生物学功能及其在肾损伤中作用的研究进展[J]. 中国急救复苏与灾害医学杂志, 2008, 3(2):121-125.
[20] 蔡志华, 卢辉山. 热休克蛋白90在防治肿瘤方面的研究进展[J]. 医学综述, 2008, 14(4):559-562.
[21] SIEBELT M, JAHR H, GROEN H C, et al. Hsp90 inhibition protects against biomechanically induced osteoarthritis in rats[J]. Arthritis & Rheumatology, 2013, 65(8):2102.
[22] 秦大强, 罗巍. 小分子热休克蛋白22与临床疾病研究进展[J]. 医学综述, 2010, 16(1):10-12.
[23] 李梢, 张博.中药网络药理学:理论、方法与应用(英文)[J].中国天然药物, 2013, 11(2):110-120.
[2] 陈娟, 顾俊菲, 汪春飞,等. 组分结构中药与网络药理学:病理机制网络的系统整体调控[J]. 中国中药杂志, 2015, 40(4):758-764.
[3] 王永华,杨凌. 基于系统药理学的现代中药研究体系[J]. 世界中医药, 2013, 8(7):801-808.
[4] SHI XL, LIU K, WU LG. Interventional value of total flavonoids from Rhizoma Drynariae on Cathepsin K, a potential target of osteoporosis[J].CHIN J INTEGR MED, 2011, 17(7):556-560.
[5] MA X, LV J, SUN X, et al. Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3A expression in denervated bone[J]. Scientific Reports, 2016, 25(6):24562.
[6] 王文刚.黄酮类中药单体柚皮素抑制破骨细胞的研究[D]. 上海:上海交通大学,2015.
[7] MOKDAD-BZEOUICH I, MUSTAPHA N, SASSI A, et al. Investigation of immunomodulatory and anti-inflammatory effects of eriodictyol through its cellular anti-oxidant activity[J]. Cell Stress & Chaperones, 2016, 21(5):1-9.
[8] 季鹏, 赵文明, 于桐.柚皮素的最新研究进展[J].中国新药杂志, 2015,24(12): 1382-1386.
[9] 宋双红, 王德, 莫易易,等. 柚皮素防治去卵巢致大鼠骨质疏松症的实验研究[J]. 药学学报, 2015,50(2):154-161.
[10] 翟远坤, 潘亚磊, 牛银波,等. 柚皮苷及其代谢物柚皮素对乳鼠颅骨成骨细胞分化成熟影响的比较研究[J]. 中国药学杂志, 2013, 48(16):1373-1379.
[11] PANG W Y, WANG X L, SAUKENG M, et al. Naringin improves bone properties in ovariectomized mice and exerts oestrogen-like activities in rat osteoblast-like (UMR-106) cells[J]. British Journal of Pharmacology, 2010, 159(8):1693-1703.
[12] 吴新涛, 石晶, 高乐才,等. 柚皮素对氧化应激所致成骨细胞凋亡的影响及机制研究[J]. 河北医药, 2016, 38(19):2915-2918.
[13] 张亦凡, 刘功关, 刘茜,等. 圣草酚抑制自由基诱导的生物大分子损伤及对肝癌细胞HepG2毒性的作用[J]. 食品科学, 2013, 34(17):126-130.
[14] SONG F, ZHOU L, ZHAO J, et al. Eriodictyol Inhibits RANKL-Induced Osteoclast Formation and Function via Inhibition of NFATc1 Activity[J]. Journal of Cellular Physiology, 2016, 231(9):1983.
[15] LI L, ZENG Z, CAI G. Comparison of neoeriocitrin and naringin on proliferation and osteogenic differentiation in MC3T3-E1[J]. Phytomedicine, 2011, 18(11):985-989.
[16] 徐永跃, 黄清春, 何羿婷,等. COX-2/TxA_2通路在炎症相关疾病中的分子机制研究进展[J]. 中国中西医结合杂志, 2017, 37(6):763-767.
[17] 李洋, 陈前昭, 邵英,等. 骨形态蛋白9诱导干细胞骨向分化与环氧酶-2及PI3K/Akt的关系研究[J]. 中国药理学通报, 2017, 33(7):908-915.
[18] 郭晓华, 李俊萍, 张昕.阿托伐他汀通过促进热休克蛋白90表达减少急诊经皮冠状动脉介入治疗术后对比剂肾病的发生率[J].中国循环杂志, 2015, 30(9):845-48.
[19] 李润玖, 李锐, 张彧. 热休克蛋白生物学功能及其在肾损伤中作用的研究进展[J]. 中国急救复苏与灾害医学杂志, 2008, 3(2):121-125.
[20] 蔡志华, 卢辉山. 热休克蛋白90在防治肿瘤方面的研究进展[J]. 医学综述, 2008, 14(4):559-562.
[21] SIEBELT M, JAHR H, GROEN H C, et al. Hsp90 inhibition protects against biomechanically induced osteoarthritis in rats[J]. Arthritis & Rheumatology, 2013, 65(8):2102.
[22] 秦大强, 罗巍. 小分子热休克蛋白22与临床疾病研究进展[J]. 医学综述, 2010, 16(1):10-12.
[23] 李梢, 张博.中药网络药理学:理论、方法与应用(英文)[J].中国天然药物, 2013, 11(2):110-120.