Traditional Chinese Medicine（TCM）, a crucial component of the current medical system, has been extensively used in clinical practice due to its valuable therapeutic efficacy, and its potentials as an important sourc...Traditional Chinese Medicine（TCM）, a crucial component of the current medical system, has been extensively used in clinical practice due to its valuable therapeutic efficacy, and its potentials as an important source of new pharmacophores. TCM is characterized by holistic theory, which emphasizes maintaining the balance of the patient＇s whole body using herbal formulae（fangji in Chinese） composed of mixtures of herbs with multiple bioactive ingredients. Because of the complex nature of these formulae, it is necessary to develop systematic methods to identify their bioactive ingredients and to clarify their mechanisms of action. With the rapid progress in bioinformatics, systems biology, and polypharmacology, ＂network pharmacology＂, which shifts the ＂one target, one drug＂ paradigm to the ＂network target, multi-component＂ strategy, has attracted the attention because it can not only reveal the underlying complex interactions between a herbal formula and cellular proteins but detect the influence of their interactions on the function and behavior of the system. Growing evidence shows that the network pharmacology strategy can be a powerful approach to modern research on TCM. The present paper focuses on the basis of network pharmacology and the recent progress in its methodology, illustrates its utility in screening bioactive ingredients and elucidating the mechanisms of action of TCM herbal formulae, analyzes its limitations and problems, and discusses its development direction and application prospects.展开更多
构建柴胡活性成分-作用靶点网络和蛋白相互作用网络,对靶点涉及的功能和通路进行分析,探讨柴胡抗抑郁的作用机制。通过TCMSP数据库、文献挖掘和本实验室已有研究获取柴胡主要活性成分,利用DRAR-CPI服务器、Gene Cards和OMIM数据库预测...构建柴胡活性成分-作用靶点网络和蛋白相互作用网络,对靶点涉及的功能和通路进行分析,探讨柴胡抗抑郁的作用机制。通过TCMSP数据库、文献挖掘和本实验室已有研究获取柴胡主要活性成分,利用DRAR-CPI服务器、Gene Cards和OMIM数据库预测和筛选柴胡活性成分抗抑郁的作用靶点。采用Cytoscape软件构建活性成分-作用靶点网络,采用String数据库和Cytoscape软件绘制蛋白相互作用网络,通过Systems Dock Web Site对成分与靶点进行分子对接验证。采用DAVID数据库对靶点进行GO及KEGG通路分析,通过Dis Ge NET数据库对靶点所属的类型进行归属。筛选得到柴胡15个活性成分,涉及50个作用靶点。网络分析结果表明,柴胡主要涉及细胞过程、代谢过程、对应激的应答等生物过程,通过调节PI3K-AKT、MAPK、Rap1、Ras、Fox O和neurotrophin等信号通路来发挥抗抑郁作用。本研究体现了柴胡多成分-多靶点-多途径的作用特点,为进一步开展柴胡抗抑郁作用机制的研究提供了新思路和新方法。展开更多
Traditional Chinese medicine(TCM)is a precious treasure of the Chinese nation and has unique advantages in the prevention and treatment of diseases.The holistic view of TCM coincides with the new generation of medical...Traditional Chinese medicine(TCM)is a precious treasure of the Chinese nation and has unique advantages in the prevention and treatment of diseases.The holistic view of TCM coincides with the new generation of medical research paradigm characterized by network and system.TCM gave birth to a new method featuring holistic and systematic"network target",a core theory and method of network pharmacology.TCM is also an important research object of network pharmacology.TCM network pharmacology,which aims to understand the network-based biological basis of complex diseases,TCM syndromes and herb treatments,plays a critical role in the origin and development process of network pharmacology.This review introduces new progresses of TCM network pharmacology in recent years,including predicting herb targets,understanding biological foundation of diseases and syndromes,network regulation mechanisms of herbal formulae,and identifying disease and syndrome biomarkers based on biological network.These studies show a trend of combining computational,experimental and clinical approaches,which is a promising direction of TCM network pharmacology research in the future.Considering that TCM network pharmacology is still a young research field,it is necessary to further standardize the research process and evaluation indicators to promote its healthy development.展开更多
Diabetic nephropathy(DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease,which causes serious health problems and great financial burden to human ...Diabetic nephropathy(DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease,which causes serious health problems and great financial burden to human society worldwide.Conventional strategies,such as renin-angiotensinaldosterone system blockade,blood glucose level control,and bodyweight reduction,may not achieve satisfactory outcomes in many clinical practices for DN management.Notably,due to the multi-target function,Chinese medicine possesses promising clinical benefits as primary or alternative therapies for DN treatment.Increasing studies have emphasized identifying bioactive compounds and molecular mechanisms of reno-protective effects of Chinese medicines.Signaling pathways involved in glucose/lipid metabolism regulation,antioxidation,anti-inflammation,anti-fibrosis,and podocyte protection have been identified as crucial mechanisms of action.Herein,we summarize the clinical efficacies of Chinese medicines and their bioactive components in treating and managing DN after reviewing the results demonstrated in clinical trials,systematic reviews,and meta-analyses,with a thorough discussion on the relative underlying mechanisms and molecular targets reported in animal and cellular experiments.We aim to provide comprehensive insights into the protective effects of Chinese medicines against DN.展开更多
Background Hypertensive target organ damage （TOD） is the main reason for mortality or disability in elderly hypertensive patients. The studies on TOD of hypertension in Asia, especially in Chinese elderly hypertensi...Background Hypertensive target organ damage （TOD） is the main reason for mortality or disability in elderly hypertensive patients. The studies on TOD of hypertension in Asia, especially in Chinese elderly hypertensive patients, are very limited. The aim of this study was to evaluate the prevalence and correlative factors of TOD in older Chinese hypertensive inpatients. Methods This is a retrospective survey and data were collected from the computerized medical files of hypertensive inpatients from January of 1993 to December of 2008. The analysis was done on 17 682 inpatients, aged 60 years or older, with a diagnosis of essential hypertension （EH）. The evidence of hypertensive TOD and associated factors with TOD were collected. Results The prevalence of any hypertensive target organ involvement among these subjects was high. In multivariable Logistic regressions adjusted for potentially confounding factors, older age, male gender, diabetes, EH grade 3, systolic blood pressure （SBP）, and low-density lipoprotein cholesterol （LDL-C）, were independently associated with coronary artery disease. Age, duration of EH, EH grade 3, SBP, pulse pressure （PP）, and homocysteine （Hcy） were independently associated with cerebrovascular disease. Age, diabetes, duration of EH, EH grade 3, SBP, PP and estimated glomerular filtration rate （eGFR） were independently associated with chronic kidney disease. Male gender, EH grade 3 and SBP were independently associated with aortic dissection. Conclusions The prevalence of hypertensive TOD is high in older Chinese hypertensive inpatients. Various cardiovascular risk factors are associated with hypertensive TOD. The level of SBP and severe hypertension （grade 3 hypertension） are common independent risk factors of TOD.展开更多
Idiopathic pulmonary fibrosis(IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure.Recently, phosphatidyli...Idiopathic pulmonary fibrosis(IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure.Recently, phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3 K/AKT in fibrotic processes is increasingly prominent, with PI3 K/AKT inhibitors currently under clinical evaluation in IPF. Therefore,PI3 K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3 K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3 K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future.展开更多
基金National Natural Science Foundation of China(81225025)Beijing Nova Program(Z1511000003150126)
文摘Traditional Chinese Medicine（TCM）, a crucial component of the current medical system, has been extensively used in clinical practice due to its valuable therapeutic efficacy, and its potentials as an important source of new pharmacophores. TCM is characterized by holistic theory, which emphasizes maintaining the balance of the patient＇s whole body using herbal formulae（fangji in Chinese） composed of mixtures of herbs with multiple bioactive ingredients. Because of the complex nature of these formulae, it is necessary to develop systematic methods to identify their bioactive ingredients and to clarify their mechanisms of action. With the rapid progress in bioinformatics, systems biology, and polypharmacology, ＂network pharmacology＂, which shifts the ＂one target, one drug＂ paradigm to the ＂network target, multi-component＂ strategy, has attracted the attention because it can not only reveal the underlying complex interactions between a herbal formula and cellular proteins but detect the influence of their interactions on the function and behavior of the system. Growing evidence shows that the network pharmacology strategy can be a powerful approach to modern research on TCM. The present paper focuses on the basis of network pharmacology and the recent progress in its methodology, illustrates its utility in screening bioactive ingredients and elucidating the mechanisms of action of TCM herbal formulae, analyzes its limitations and problems, and discusses its development direction and application prospects.
文摘构建柴胡活性成分-作用靶点网络和蛋白相互作用网络,对靶点涉及的功能和通路进行分析,探讨柴胡抗抑郁的作用机制。通过TCMSP数据库、文献挖掘和本实验室已有研究获取柴胡主要活性成分,利用DRAR-CPI服务器、Gene Cards和OMIM数据库预测和筛选柴胡活性成分抗抑郁的作用靶点。采用Cytoscape软件构建活性成分-作用靶点网络,采用String数据库和Cytoscape软件绘制蛋白相互作用网络,通过Systems Dock Web Site对成分与靶点进行分子对接验证。采用DAVID数据库对靶点进行GO及KEGG通路分析,通过Dis Ge NET数据库对靶点所属的类型进行归属。筛选得到柴胡15个活性成分,涉及50个作用靶点。网络分析结果表明,柴胡主要涉及细胞过程、代谢过程、对应激的应答等生物过程,通过调节PI3K-AKT、MAPK、Rap1、Ras、Fox O和neurotrophin等信号通路来发挥抗抑郁作用。本研究体现了柴胡多成分-多靶点-多途径的作用特点,为进一步开展柴胡抗抑郁作用机制的研究提供了新思路和新方法。
基金supported by the National Natural Science Foundation of China(Nos.6201101081,81630103 and 81225025)Tsinghua University Spring Breeze Fund(No.2020-Z99CFY040)Beijing National Research Center for Information Science and Technology(Nos.BNR2019TD01020 and BNR2019-RC01012)。
文摘Traditional Chinese medicine(TCM)is a precious treasure of the Chinese nation and has unique advantages in the prevention and treatment of diseases.The holistic view of TCM coincides with the new generation of medical research paradigm characterized by network and system.TCM gave birth to a new method featuring holistic and systematic"network target",a core theory and method of network pharmacology.TCM is also an important research object of network pharmacology.TCM network pharmacology,which aims to understand the network-based biological basis of complex diseases,TCM syndromes and herb treatments,plays a critical role in the origin and development process of network pharmacology.This review introduces new progresses of TCM network pharmacology in recent years,including predicting herb targets,understanding biological foundation of diseases and syndromes,network regulation mechanisms of herbal formulae,and identifying disease and syndrome biomarkers based on biological network.These studies show a trend of combining computational,experimental and clinical approaches,which is a promising direction of TCM network pharmacology research in the future.Considering that TCM network pharmacology is still a young research field,it is necessary to further standardize the research process and evaluation indicators to promote its healthy development.
基金financially supported by General Research Fund from the Research Grant Council,Hong Kong Special Administrative Region(Project code:17152116,China)Health and Medical Research Fund from the Food and Health Bureau,Hong Kong Special Administrative Region(Project codes:15162961,16172751,and 17181101,China)+2 种基金Wong’s Donation(Project code:200006276,China)a donation from the Gaia Family Trust of New Zealand(Project code:200007008,New Zealand)a contract research(Project code:CR-BL03,New Zealand)
文摘Diabetic nephropathy(DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease,which causes serious health problems and great financial burden to human society worldwide.Conventional strategies,such as renin-angiotensinaldosterone system blockade,blood glucose level control,and bodyweight reduction,may not achieve satisfactory outcomes in many clinical practices for DN management.Notably,due to the multi-target function,Chinese medicine possesses promising clinical benefits as primary or alternative therapies for DN treatment.Increasing studies have emphasized identifying bioactive compounds and molecular mechanisms of reno-protective effects of Chinese medicines.Signaling pathways involved in glucose/lipid metabolism regulation,antioxidation,anti-inflammation,anti-fibrosis,and podocyte protection have been identified as crucial mechanisms of action.Herein,we summarize the clinical efficacies of Chinese medicines and their bioactive components in treating and managing DN after reviewing the results demonstrated in clinical trials,systematic reviews,and meta-analyses,with a thorough discussion on the relative underlying mechanisms and molecular targets reported in animal and cellular experiments.We aim to provide comprehensive insights into the protective effects of Chinese medicines against DN.
文摘Background Hypertensive target organ damage （TOD） is the main reason for mortality or disability in elderly hypertensive patients. The studies on TOD of hypertension in Asia, especially in Chinese elderly hypertensive patients, are very limited. The aim of this study was to evaluate the prevalence and correlative factors of TOD in older Chinese hypertensive inpatients. Methods This is a retrospective survey and data were collected from the computerized medical files of hypertensive inpatients from January of 1993 to December of 2008. The analysis was done on 17 682 inpatients, aged 60 years or older, with a diagnosis of essential hypertension （EH）. The evidence of hypertensive TOD and associated factors with TOD were collected. Results The prevalence of any hypertensive target organ involvement among these subjects was high. In multivariable Logistic regressions adjusted for potentially confounding factors, older age, male gender, diabetes, EH grade 3, systolic blood pressure （SBP）, and low-density lipoprotein cholesterol （LDL-C）, were independently associated with coronary artery disease. Age, duration of EH, EH grade 3, SBP, pulse pressure （PP）, and homocysteine （Hcy） were independently associated with cerebrovascular disease. Age, diabetes, duration of EH, EH grade 3, SBP, PP and estimated glomerular filtration rate （eGFR） were independently associated with chronic kidney disease. Male gender, EH grade 3 and SBP were independently associated with aortic dissection. Conclusions The prevalence of hypertensive TOD is high in older Chinese hypertensive inpatients. Various cardiovascular risk factors are associated with hypertensive TOD. The level of SBP and severe hypertension （grade 3 hypertension） are common independent risk factors of TOD.
基金supported by the National Natural Science Foundation of China(No.82003873)the Postdoctoral Science Foundation of China(No.2020M681899)the Zhejiang Provincial Natural Science Foundation of China(No.LR21H310001)。
文摘Idiopathic pulmonary fibrosis(IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure.Recently, phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3 K/AKT in fibrotic processes is increasingly prominent, with PI3 K/AKT inhibitors currently under clinical evaluation in IPF. Therefore,PI3 K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3 K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3 K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future.
