| Background:Traditional Chinese Medicine(TCM)property theory is the important part of the TCM theory.It is a summary of the clinical function and mechanism of herbs.And it is the main basis of clinic prescription.Understanding the relationship between TCM property and its efficacy in the perspective of modern science helps to guide the research and development of TCM.Objective:This study researched the generated relationship between the bitter of TCM and its efficacy of heat-clearing and detoxifying(EHD),and efficacy of promoting blood circulation and removing the blood stasis(EPR)from different scales.In order to research the EHD and EPR which expressed by bitter,the property-efficacy network which based on relationship as background and strategy was put forward.Based on different scales network,the whole research idea was designed and the research contents were divided into three parts:bitter of TCM,EHD and EPR,and verification of relevant targets.On the basis of these three parts,TCM property-pharmacology network,efficacy-pharmacology network,then researched the bitter-efficacy relationships which between bitter and EHD,bitter and EPR were constructed on the macro level;Protein-protein interaction network(PPI)based on the interaction of proteins were constructed,network modularization by module analysis method were carried out,the bitter-efficacy relationships which between bitter and EHD,bitter and EPR were researched on the mesoscopic level;Based on the signal transmission between the cells,the cell signaling pathway network of EHD,and coronary heart disease(CHD)treated by EPR which expressed by bitter were constructed,the bitter-efficacy relationships which between bitter and EHD,bitter and EPR were researched on the micro level and the effective components cluster of TCM were identified based on the taste efficacy-disease network.Methods and results:1.Property-efficacy relationship studiesthat based on pharmacology on the macro level.1)The confirmation of bitter targets of taste and efficacy.Defined other targets which affected by bitter ligand as bitter taste targets,the target set which had a strong rule and affected by components in bitter TCM as bitter efficacy targets.Discussed the consistency of taste and efficacy bitter by the comparison of their same targets and the same pharmacology of different targets.2)The targets of bitter efficacy,EHD and EPR were confirmed.The targets which affected by the TCM of bitter,EHD and EPR were collected.The databases of the property of bitter TCM-pharmacology-components-targets,the EHD TCM-pharmacology-components-target,EPR TCM pharmacology-components-targets were constructed respectively.The taste-efficacy relationships which between bitter and EHD,bitter and EPR were discussed on the macro level by calculating the bitter related pharmacology and targets,EHD related pharmacology and targets,EPR related pharmacology and targets,and the similarities and differences among the pharmacology of these three parts were compared.Meanwhile,related targets that we got could be used in the subsequent construction of PPI and cellular signaling network.Results show that bitter expression of EHD and EPR related many pharmacological effects such as anti-inflammatory,antibacterial,antitumor,immunosuppression,cardiac,hypolipidemic,sedation,antivirus,inhibiting platelet aggregation,diuretic,anti-myocardial ischemia,hepatoprotective,analgesic,anti-oxidant,cholagogue,anti-ulcer,immune promotion,and antihypertensive.Different pharmacological effects are different in the degree of association.2.Property-efficacy relationship studies that based on the functional module on the mesoscopic level.1)The conformation of network constructed method.With the entity grammar system(EGS)as theoretical foundation,the PPI network of bitter efficacy,EHD,EPR and cellular signal transmission network was constructed by network qualitative simulation,and the reliability of network was analyzed by network topological properties.2)The PPI network was analyzed by module analysis,the module identificationalgorithmwas also investigated.The MCL was confirmed as module clusteringalgorithm,and the evaluation index were module function consistency and the value of F.3)The module identification of bitter efficacy,EHD,and EPR efficacy PPI network were carried out by MCL algorithm.The module function was confirmed by GO annotation.The relationship which between bitter and EHD,and EPR on the mesoscopic level was studied by the similarities and differences among their functional modules.Results show that bitter expression of EHD and EPR related many biological processes such as positive regulation of cellular process,G-protein coupled receptor signaling pathway,arachidonic acid metabolic process,lipid metabolic process,potassium ion transmembrane transport,regulation of transmembrane transport,inflammatory response,response to virus,regulation of heart rate,regulation of cardiac muscle contraction,nucleoside phosphate metabolic process,nucleoside phosphate biosynthetic process,toll-like receptor 5 signaling pathway,toll-like receptor 10 signaling pathway,response to lipopolysaccharide,response to molecule of bacterial origin,gamma-aminobutyric acid signaling pathway,chloride transmembrane transport,bicarbonate transport,regulation of intracellular pH,steroid hormone mediated signaling pathway,regulation of lipoprotein lipase activity,behavioral response to nicotine,synaptic transmission,progesterone receptor signaling pathway,mammary gland epithelium development,nitric oxide metabolic process and regulation of nitric-oxide synthase activity.3.Property-efficacy relationship studies that based on the cell signaling pathwaynetwork on the micro level.1)With the cell signaling pathway network as background,property-efficacy targets as starting point,and disease targets as ending point,the disease treatment network which based on property-efficacy was constructed.To facilitate the therapeutic mechanism elucidation,the network was simplified by the shortest path extraction method.The similarities and differences among bitter,EHD,and EPR in the disease treatment were researched on the micro level.2)The disease treatment targets of property-efficacy according to the disease treatment network were determined,the effective components cluster of the corresponding TCM and elucidate the material basis which generated property-efficacy were.The result showed that the treatment targets of coronary heart disease screened by the bitter-EHD including:Dipeptidyl peptidase 4(DPP4),Androgen receptor(AR),Beta-2 adrenergic receptor(ADRB2),Peroxisome proliferator-activated receptor gamma(PPARG),Glucocorticoid receptor(NR3C1),Serum paraoxonase/arylesterase 1(PON1),Nitric oxide synthase 3(NOS3),Muscarinic acetylcholine receptor M3(CHRM3),Retinoic acid receptor alpha(RXRA),protein tyrosine phosphatase,non-receptor type 1(PTPN1),Heat shock protein 90 alpha(HSP90AA1)and prothrombin(F2).Comparing with the above result,the treatment targets of coronary heart disease screened by the bitter-EPR have more than three targets,including:Aldose reductase(AKR1B1),Tumor necrosis factor receptor superfamily member 6(FAS)and Sodium dependent dopamine transporter(SLC6A3).Conclusions:In order to solve the key scientific problems of property-efficacy relationship,property-efficacy relationship network were constructed under the different scales based on the relationship of the medicinal efficacy of biological network building technology.The unique ideas and methods were set up to explain the mechanism of bitter expression of EHD and EPR in different aspects,and it is of great significance to reveal the modern biological mechanism of property. |
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