| Most of pungent/bitter Traditional Chinese medicine(TCM)which can activate blood and dissolve stasis are often used for the treatment of cardiovascular diseases with significant effects.Different tastes will lead to different efficacy.Therefore,further study of mechanism helps to explain the intrinsic relevance of TCM’s taste and efficacy.On the basis of the pharmacological research on Chinese medicine for activating blood and removing stasis,the systematic research on the microscopic level will be more helpful to explain the drugs’ regulation on the organism and explore the mechanism of blood-activating stasis-resolving herbs with a bitter/pungent taste.Biological network method is an interdisciplinary subject that has been developing rapidly in recent years.It not only accords with the theory of TCM to depict human life activities from a holistic perspective,but also shows the interaction between biomolecules at the micro level.As an important part of biological network,metabolic network is an abstract expression of a series of complex and orderly human biochemical reactions and metabolic pathways.The quantitative metabolic network adding with certain data and algorithm conducts quantitative analysis on the relationship between drug and target and the relationship between target and target in metabolic network by establishing a mathematical model,which analyzes the law of change in its quantity.This method can more accurately describe the effect of drugs on human metabolic networks and can be used to predict and judge potential active compounds.Calculating and analyzing data of the action of pungent/bitter TCM which can activate blood and dissolve stasis on the metabolic pathway of human body based on the quantitative metabolic network,so as to reveal the relationship between the components of TCM and the biological molecular network of human body is helpful to explain systematically the mechanism of the effect of the pungent/bitter TCM which can activate blood and dissolve stasis.In this paper,the herb-component-target network was constructed with 9 blood-activating stasis-resolving herbs as the carrier.Networks with same tastes were fused.Then,pungent taste target network,bitter taste target network,pungent and bitter taste network were obtained.Comparing and analyzing these three networks,pharmacological effects of herbs with same tastes and different tastes were illustrated,respectively.The lipid metabolic network which was co-regulation by three kinds of herbs was selected to construct quantitative metabolic network model.It can predict the lipid lowering effect of the ingredients of TCM.Finally,the results of the network quantitative analysis were further verified by cell biological experiments.This study provides new ideas for the mechanism research of traditional Chinese medicine.This study includes four aspects:1.Establishment of medicinal taste characteristic networkA representative sample of 9 pungent/bitter TCM which can activate blood and dissolve stasis was selected.Based on data mining and virtual screening of pharmacophores,information of Chinese medicine ingredients and their targets were collected to construct the herbcomponent-target networks.Three kinds of targets were obtained by fusing networks with same tastes.Through the pathway annotation of these targets,it was found that the three kinds of targets were all involved in signal transduction,metabolic system,immune system,coagulation.and biological stress and other metabolic pathways.The number of targets of pungent/bitter TCM participating in the same metabolic pathway is different.It shows the consistency and specificity of the three types of herbs that have the same efficacy,and provides data support for mechanism research of TCM and study on correlation between taste and efficacy.2.Correlation between TCM’s taste and efficacySeeking the intersection and complement of the three types of targets,it is divided into seven regions.They are divided into seven regions.Pharmacological effects of herbs with same tastes and different tastes were illustrated.The experimental results showed that pungent/bitter TCM which can activate blood and dissolve stasis were involved in the processes of cancer,inflammation/immune,lipid metabolism,coagulation,and vascular injury,and so on.The unique targets of pungent TCM are mainly involved in the regulation of lipid metabolism;the unique targets of bitter TCM are mainly involved in the regulation of coagulation and lipid metabolism;the unique targets of pungent&bitter taste are mainly involved in the regulation of the development and progression of cancer;the intersection targets of pungent and bitter tastes is mainly involved in regulation of inflammation and nervous system;pungent and pungent&bitter taste intersections targets are mainly involved in regulation of inflammation and energy metabolism;the intersection targets of bitterness and pungent&bitter taste are mainly involved in the regulation of endothelial injury,vascular neovascularization,and diabetes.Herbs with different tastes have their own characteristics,these characteristics were similar to the efficacy of pungent/bitter TCM in TCM theory.It is helpful to explain correlation between taste and efficacy of the pungent/bitter TCM which can activate blood and dissolve stasis.3.Analysis method based on quantitative metabolic networkThe lipid metabolic network which was co-regulation by three kinds of herbs was selected to construct quantitative metabolic network model.Based on the topological parameters,the scale-free nature,small-world nature,connectivity,and heterogeneity of the networks built were evaluated.It shows that the network built is reasonable.This study explored the quantitative analysis method of networks through docking and Dijkstra algorithm,and then,the effect of components of TCM on reducing lipid metabolism is calculated.The potential effective components such as curcumin,Curcumin,Normethoxycurcumin,etc were obtained.This study constructed HepG2 cell fat accumulation model,this model was used to verify the activity of medicinal ingredients.The results showed that the optimal concentration of Comp.1-curcumin in Turmeric was 30μmol/L,which could reduce the percentage of TG by 34.09%.The optimal concentration of Comp.2-curcumin in Turmeric was 30 μmol/L,which could reduce the percentage of TG by 20.11%.This method evaluates the reliability of quantitative metabolic networks at the cellular level.It provides a new methods for mechanism research of TCM.4.Quantitative Analysis of mechanism of the pungent/bitter TCM which can activate blood and dissolve stasisBased on the established quantitative lipid metabolism network model,the lipid-lowering efficacy of Chinese herbal components was calculated.The key lipid-lowering efficacy ingredients were identified.The quantitative results were analyzed based on literature mining.The potential lipid-lowering efficacy ingredient were obtained.The pungent/bitter TCM which can activate blood and dissolve stasis all have a certain lipid-lowering effect,which reflects the efficacy of Xin Xing Ku Xie.Comparing the quantity of effective components of pungent/bitter TCM,The number of effective components of bitter TCM is more than that of other two kinds of medicine.This method analyzes the mechanism of TCM from the overall level.It illustrates the characteristics of multi-component and multi-target of Chinese medicine.At the same time,the potential lipid-lowering ingredients screened out provide material basis and research direction for lipid-lowering Chinese medicine design.This study obtained taste characteristic targets and quantitative metabolic network model with the pungent/bitter TCM which can activate blood and dissolve stasis as the carrier.It explores the pathway of TCM with different tastes,the relationship between drug taste and efficacy,and the efficacy of TCM with different tastes on lipid metabolism networks.It provide methodological support for revealing the mechanism of Chinese medicine on the molecular and systemic levels. |
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