基于中药药性理论探索“性味网络药理学”的合理性与可行性——以如金解毒散干预病毒性肺炎的性味网络药理学研究为例
Exploring the rationality and feasibility of "property and flavor network pharmacology" based on the theory of property and flavor of Chinese medicine: Taking the property and flavor network pharmacology of Rujin Jiedu Powder in treating viral pneumonia as an example
- 上海中医药大学学报 2021年35卷第6期 页码：1-11
- 作者机构：
1.上海中医药大学交叉科学研究院（上海 201203）
2.上海中医药大学附属上海市中西医结合医院（上海 200071）
- 作者简介：
陈健，男，博士，助理研究员，主要从事中药抗周围血管疾病及网络药理学研究
[ "葛广波，男，上海中医药大学研究员、特聘教授，博士生导师，交叉科学研究院常务副院长。为国家优秀青年基金获得者、国家青年岐黄学者、上海市曙光学者、上海市优秀学术带头人；兼任中华中医药学会中药实验药理分会副秘书长，中国药理学会药物代谢专业委员会青年委员会副主任委员，中国药理学会分析药理学专业委员会青年委员会副主任委员，中华中医药学会青年委员。主要研究方向：①药物代谢酶特异性配体的设计研发；②源于天然的酶抑制剂高效发现及成药性优化。先后主持国家自然科学基金优秀青年科学基金、国家自然科学基金面上项目、国家重点研发计划“中医药现代化研究”重点专项等重大科研项目10余项；在Coordin Chem Rev、J Am Chem Soc、Angew Chem Int Ed、Chem Sci、Biosens Bioelectron、ACS Appl Mater Inter、ACS Sensors、Anal Chem、J Med Chem、Acta Pharm Sin B、Analytica Chimica Acta、Chem Commun等国际权威学术期刊上发表SCI论文220余篇，SCI总被引5 000余次，H因子41。应邀担任Acta Pharm Sin B、J Ethnopharmacol、Chinese Chem Lett、Biosensors等SCI收录学术期刊及《药学学报》《中草药》《中国中药杂志》等中文核心期刊编委/青年编委；并担任J Am Chem Soc、Pharmacol Therapeut、Chem Sci、Med Res Rev、Theranostics、Biosens Bioelectron、ACS Appl Mater Inter、J Med Chem、Anal Chem、Acta Pharm Sin B、Analytica Chimica Acta、Chem Commun等100余种学术期刊审稿人。应邀担任国家自然科学基金委员会医学部函评及会评专家、香港研究资助局项目评审专家。先后荣获中国药学会以岭生物医药青年奖、中华中医药学会中青年创新人才奖、青年岐黄学者、上海市青年五四奖章、中国药理学会刘昌孝人才奖励基金“优秀青年科技工作者奖”等荣誉，并入选2020药学领域全球2%顶尖科学家榜。" ]
[ "陈启龙，男，博士，教授、研究员，上海中医药大学交叉科学研究院硕士生导师。主要从事中医药大数据及精准医疗、中药抗肿瘤分子机制、CRISPR药物靶点筛选、网络药理学等研究，为中国民族医药学会信息与大数据专业委员会常务理事、世界中医药联合会网络药理学专业委员会理事、中国中西医结合学会循证医学专业委员会委员、上海市中西医结合学会系统生物学委员会委员。主持、参与国家自然科学基金面上项目及重点项目、国家重点研发计划“中医药现代化研究”专项项目、上海市自然科学基金面上项目等。先后在J Invest Dermatol、Protein & Cell、Clin & Trans Med、Int J Mol Sci、Mol Cells、Mol Biosys等国际权威学术期刊上发表SCI论文40余篇；应邀担任Front Cell DevBiol、《中草药》等期刊编委，并担任J Ethnopharmacol、Chin J Nat Med、Front Pharmacol等10余种学术期刊的审稿人。" ]
- 基金信息：国家自然科学基金青年基金项目(82104873);上海市自然科学基金面上项目(19ZR1452100);上海市“科技创新行动计划”生物医药科技支撑专项项目(21S21900600);上海市青年科技英才扬帆计划项目(20YF1445900);上海市卫健委临床研究专项项目(20194Y0081);上海市虹口区卫健委中医药科研课题项目(HKQ-ZYY-2020-19);上海中医药大学“杏林百人”计划项目(RCPY0040)
DOI：10.16306/j.1008-861x.2021.06.001
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陈健, 汤琛琛, 赵堃鹏, 等. 基于中药药性理论探索“性味网络药理学”的合理性与可行性——以如金解毒散干预病毒性肺炎的性味网络药理学研究为例[J]. 上海中医药大学学报, 2021,35(6):1-11.
CHEN Jian, TANG Chenchen, ZHAO Kunpeng, et al. Exploring the rationality and feasibility of "property and flavor network pharmacology" based on the theory of property and flavor of Chinese medicine: Taking the property and flavor network pharmacology of Rujin Jiedu Powder in treating viral pneumonia as an example[J]. Academic Journal of Shanghai University of Traditional Chinese Medicine, 2021,35(6):1-11.
陈健, 汤琛琛, 赵堃鹏, 等. 基于中药药性理论探索“性味网络药理学”的合理性与可行性——以如金解毒散干预病毒性肺炎的性味网络药理学研究为例[J]. 上海中医药大学学报, 2021,35(6):1-11. DOI： 10.16306/j.1008-861x.2021.06.001.
CHEN Jian, TANG Chenchen, ZHAO Kunpeng, et al. Exploring the rationality and feasibility of "property and flavor network pharmacology" based on the theory of property and flavor of Chinese medicine: Taking the property and flavor network pharmacology of Rujin Jiedu Powder in treating viral pneumonia as an example[J]. Academic Journal of Shanghai University of Traditional Chinese Medicine, 2021,35(6):1-11. DOI： 10.16306/j.1008-861x.2021.06.001.
摘要
目的：,2,基于中药药性理论，首次提出“性味网络药理学”概念，通过构建中药性味网络并结合分子对接技术，探索经典方剂如金解毒散治疗病毒性肺炎的作用机制。,方法：,2,从HERB数据库获取如金解毒散主要成分，GeneCards收集病毒性肺炎相关基因，借助NetInfer和BATMAN-TCM数据库构建如金解毒散性味药物模块的成分－靶点－疾病模型相互关系网络。采用Metascape软件对靶点进行蛋白相互作用网络和KEGG分析；采用Vina软件对成分和靶蛋白进行分子对接验证；采用SwissADME软件进行有效成分药物代谢动力学评价。,结果：,2,利用中药数据库共筛选出该方有效成分335个，其中桔梗20个，甘草117个，黄连26个，黄芩62个，黄柏75个，山栀35个。按3种性味模块进行靶点预测及网络构建，其中苦辛平模块（桔梗）潜在靶标596个，甘平模块（甘草）潜在靶标819个，苦寒模块（黄连、黄芩、黄柏、山栀）潜在靶标1 097个。网络分析及分子对接结果显示，异甘草黄素、穿贝海绵甾醇、吴茱萸次碱、草香豆酮、黄芩素、槲皮素、木犀草素等是该方治疗病毒性肺炎的重要活性成分；SRC、FYN、LCK、MET、AKT1、ABL1、MAPK8、ITK、CCR5、TP53、PTPN11、EIF2AK2、MAPK1、PIK3CD、MAPK3、BTK、STAT3、PIK3CA、MAPK14等是该方治疗病毒性肺炎的核心靶蛋白；JAK-STAT信号通路、细胞因子－细胞因子受体相互作用等是该方治疗病毒性肺炎的关键信号通路。,结论：,2,本研究通过性味网络药理学及分子对接技术揭示了如金解毒散多组分、多靶点、多通路的特点，为进一步探索如金解毒散治疗病毒性肺炎作用机制提供了新的思路与方法。研究也表明，采用性味药物模块成分－靶点－疾病模型探析中药复方物质基础具有一定的合理性与可行性。
Abstract
Objective:,2,Based on the theory of property and flavor of Chines e medicine, the concept of "property and flavor network pharmacology" is proposed for the first time. The aim is to explore the mechanism of classical prescriptions Rujin Jiedu Powder in the treatment of viral pneumonia by constructing property and flavor network of Chinese medicine combined with molecular docking technology.,Methods:,2,The main components of Rujin Jiedu Powder were obtained from HERB database, and viral pneumonia related genes were collected by GeneCards. NetInfer and BATMAN-TCM databases were used to construct the relationship network of property and flavor module component-target-disease model for Rujin Jiedu Powder. The protein-protein interaction network and KEGG analysis for targets were performed by Metascape software. Molecular docking verification of components and target proteins were performed by Vina software. The pharmacokinetics of the active components was evaluated by SwissADME software.,Results:,2,A total of 335 active components of this prescription were screened out using Chinese medicine databases, among 20 components from Platycodonis Radix, 117 components from Glycyrrhizae Radix et Rhizoma, 26 components from Coptidis Rhizoma, 62 components from Scutellariae Radix, 75 components from Phellodendri Chinensis Cortex and 35 components from Gardenia Fructus. Target prediction and network construction were carried out according to three kinds of property-flavor modules, and there were 596 potential targets in bitter-pungent-calm module(Platycodonis Radix), 819 potential targets in sweet-calm module(Glycyrrhizae Radix et Rhizoma) and 1 097 potential targets in bitter-cold module(Coptidis Rhizoma, Scutellariae Radix, Phellodendri Chinensis Cortex, Gardenia Fructus) . Network analysis and molecular docking results showed the important active components(Isolicoflavonol, Clionasterol, Rutaecarpine, Licocoumarone, Baicalein, Quercetin and Luteolin), core target proteins(SRC, FYN, LCK, MET, AKT1, ABL1, MAPK8, ITK, CCR5, TP53, PTPN11, EIF2AK2, MAPK1, PIK3CD, MAPK3, BTK, STAT3, PIK3CA, MAPK14) and key signal pathways(JAK-STAT signaling pathway, cytokine-cytokine receptor interaction) of Rujin Jiedu Powder in the treatment of viral pneumonia.,Conclusion:,2,In this study, the property and flavor network pharmacology and molecular docking are used to reveal the characteristics of multi-components, multi-targets and multi-pathways of Rujin Jiedu Powder, which provides new idea and method for further studying the mechanism of Rujin Jiedu Powder in the treatment of viral pneumonia. Research also shows that, it is reasonable and feasible to explore the material basis of Chinese medicine compound recipes by property and flavor module component-target-disease model.
关键词
性味网络药理学如金解毒散病毒性肺炎分子对接
Keywords
property and flavor network pharmacologyRujin Jiedu Powderviral pneumoniamolecular docking
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