OBJECTIVE To predict the potential targets and uncover the mechanisms of Nao De Sheng formula for the treatment of Alzheimer disease.METHODS Firstly,we collected the constituents in Nao De Sheng formula and key target...OBJECTIVE To predict the potential targets and uncover the mechanisms of Nao De Sheng formula for the treatment of Alzheimer disease.METHODS Firstly,we collected the constituents in Nao De Sheng formula and key targets toward Alzheimer disease.Then,druglikeness,oral bioavailability and blood-brain barrier permeability were evaluated to find drug-like and lead-like constituents for central nervous system diseases treatment.Finallly,we were attempted to predict the targets of constituents and find potential multi-target compounds from Nao De Sheng formula by combining the advantages of machine learning,molecular docking and pharmacophore mapping together.RESULTS Constituenttarget network,constituent-target-target network and targetbiological pathway network were built to explain the network pharmacology of the constituents in NaoD eS heng formula.CONCLUSION To the best of our knowledge,we were the first to study the mechanism of Nao De Sheng formula for potential efficacy for Alzheimer disease treatment by means of the virtual screening and network pharmacology methods.展开更多
Naodesheng(NDS) formula, which consists of Rhizoma Chuanxiong, Lobed Kudzuvine, Carthamus tinctorius, Radix Notoginseng, and Crataegus pinnatifida, is widely applied for the treatment of cardio/cerebrovascular ischemi...Naodesheng(NDS) formula, which consists of Rhizoma Chuanxiong, Lobed Kudzuvine, Carthamus tinctorius, Radix Notoginseng, and Crataegus pinnatifida, is widely applied for the treatment of cardio/cerebrovascular ischemic diseases, ischemic stroke, and sequelae of cerebral hemorrhage, etc. At present, the studies on NDS formula for Alzheimer's disease(AD) only focus on single component of this prescription, and there is no report about the synergistic mechanism of the constituents in NDS formula for the potential treatment of dementia. Therefore, the present study aimed to predict the potential targets and uncover the mechanisms of NDS formula for the treatment of AD. Firstly, we collected the constituents in NDS formula and key targets toward AD. Then, drug-likeness, oral bioavailability, and blood-brain barrier permeability were evaluated to find drug-like and lead-like constituents for treatment of central nervous system diseases. By combining the advantages of machine learning, molecular docking, and pharmacophore mapping, we attempted to predict the targets of constituents and find potential multi-target compounds from NDS formula. Finally, we built constituent-target network, constituent-target-target network and target-biological pathway network to study the network pharmacology of the constituents in NDS formula. To the best of our knowledge, this represented the first to study the mechanism of NDS formula for potential efficacy for AD treatment by means of the virtual screening and network pharmacology methods.展开更多
Cancer is a complex disease associated with multiple gene mutations and malignant phenotypes,and multi-target drugs provide a promising therapy idea for the treatment of cancer.Natural products with abundant chemical ...Cancer is a complex disease associated with multiple gene mutations and malignant phenotypes,and multi-target drugs provide a promising therapy idea for the treatment of cancer.Natural products with abundant chemical structure types and rich pharmacological characteristics could be ideal sources for screening multi-target antineoplastic drugs.In this paper,50 tumor-related targets were collected by searching the Therapeutic Target Database and Thomson Reuters Integrity database,and a multi-target anti-cancer prediction system based on mt-QSAR models was constructed by using naïve Bayesian and recursive partitioning algorithm for the first time.Through the multi-target anti-cancer prediction system,some dominant fragments that act on multiple tumor-related targets were analyzed,which could be helpful in designing multi-target anti-cancer drugs.Anti-cancer traditional Chinese medicine(TCM)and its natural products were collected to form a TCM formula-based natural products library,and the potential targets of the natural products in the library were predicted by multi-target anti-cancer prediction system.As a result,alkaloids,flavonoids and terpenoids were predicted to act on multiple tumor-related targets.The predicted targets of some representative compounds were verified according to literature review and most of the selected natural compounds were found to exert certain anti-cancer activity in vitro biological experiments.In conclusion,the multi-target anti-cancer prediction system is very effective and reliable,and it could be further used for elucidating the functional mechanism of anti-cancer TCM formula and screening for multi-target anti-cancer drugs.The anti-cancer natural compounds found in this paper will lay important information for further study.展开更多
基金The project supported by the Research Special Fund for the National Great Science and Technology Projects(2012ZX09301002,2012ZX09508104,2013ZX09402203)the International Col aboration Project(2011DFR31240)Peking Union Medical College Graduate Student Innovation Fund(2013-1007-18)
文摘OBJECTIVE To predict the potential targets and uncover the mechanisms of Nao De Sheng formula for the treatment of Alzheimer disease.METHODS Firstly,we collected the constituents in Nao De Sheng formula and key targets toward Alzheimer disease.Then,druglikeness,oral bioavailability and blood-brain barrier permeability were evaluated to find drug-like and lead-like constituents for central nervous system diseases treatment.Finallly,we were attempted to predict the targets of constituents and find potential multi-target compounds from Nao De Sheng formula by combining the advantages of machine learning,molecular docking and pharmacophore mapping together.RESULTS Constituenttarget network,constituent-target-target network and targetbiological pathway network were built to explain the network pharmacology of the constituents in NaoD eS heng formula.CONCLUSION To the best of our knowledge,we were the first to study the mechanism of Nao De Sheng formula for potential efficacy for Alzheimer disease treatment by means of the virtual screening and network pharmacology methods.
基金supported by the Research Special Fund for the National Great Science and Technology Projects(No.2012ZX09301002-001-001)the International Collaboration Project(No.2011DFR31240)Peking Union Medical College graduate student innovation fund(No.2013-1007-18)
文摘Naodesheng(NDS) formula, which consists of Rhizoma Chuanxiong, Lobed Kudzuvine, Carthamus tinctorius, Radix Notoginseng, and Crataegus pinnatifida, is widely applied for the treatment of cardio/cerebrovascular ischemic diseases, ischemic stroke, and sequelae of cerebral hemorrhage, etc. At present, the studies on NDS formula for Alzheimer's disease(AD) only focus on single component of this prescription, and there is no report about the synergistic mechanism of the constituents in NDS formula for the potential treatment of dementia. Therefore, the present study aimed to predict the potential targets and uncover the mechanisms of NDS formula for the treatment of AD. Firstly, we collected the constituents in NDS formula and key targets toward AD. Then, drug-likeness, oral bioavailability, and blood-brain barrier permeability were evaluated to find drug-like and lead-like constituents for treatment of central nervous system diseases. By combining the advantages of machine learning, molecular docking, and pharmacophore mapping, we attempted to predict the targets of constituents and find potential multi-target compounds from NDS formula. Finally, we built constituent-target network, constituent-target-target network and target-biological pathway network to study the network pharmacology of the constituents in NDS formula. To the best of our knowledge, this represented the first to study the mechanism of NDS formula for potential efficacy for AD treatment by means of the virtual screening and network pharmacology methods.
基金supported by the National Great Science Technology Projects(2018ZX09711001-003-002,2018ZX09711001-012)the National Natural Science Foundation of China(No.81673480)+2 种基金the Beijing National Science Foundation(7192134)CAMS Initiative for Innovative Medicine(CAMS-IZM)(2016-IZM-3-007)CAMS Major collaborative innovation fund for major frontier research(2020-I2M-1-003).
文摘Cancer is a complex disease associated with multiple gene mutations and malignant phenotypes,and multi-target drugs provide a promising therapy idea for the treatment of cancer.Natural products with abundant chemical structure types and rich pharmacological characteristics could be ideal sources for screening multi-target antineoplastic drugs.In this paper,50 tumor-related targets were collected by searching the Therapeutic Target Database and Thomson Reuters Integrity database,and a multi-target anti-cancer prediction system based on mt-QSAR models was constructed by using naïve Bayesian and recursive partitioning algorithm for the first time.Through the multi-target anti-cancer prediction system,some dominant fragments that act on multiple tumor-related targets were analyzed,which could be helpful in designing multi-target anti-cancer drugs.Anti-cancer traditional Chinese medicine(TCM)and its natural products were collected to form a TCM formula-based natural products library,and the potential targets of the natural products in the library were predicted by multi-target anti-cancer prediction system.As a result,alkaloids,flavonoids and terpenoids were predicted to act on multiple tumor-related targets.The predicted targets of some representative compounds were verified according to literature review and most of the selected natural compounds were found to exert certain anti-cancer activity in vitro biological experiments.In conclusion,the multi-target anti-cancer prediction system is very effective and reliable,and it could be further used for elucidating the functional mechanism of anti-cancer TCM formula and screening for multi-target anti-cancer drugs.The anti-cancer natural compounds found in this paper will lay important information for further study.
