基于生物网络调控下的中药复方多靶整合作用的研究思路与方法

世界医学发展趋势将从治疗为主到强调预防为主,从对病源的对抗治疗到重视人体的整体治疗,从集体疗法到强调个体化治疗,从重视对病灶的改善到重视生态环境的改善,从着重化学药品到重视发掘天然植物药物。并认为成功的疾病治疗模式必须使机体代谢网络中的异常或缺陷部分正常化,同时又不得干扰其他维系健康所必须的代谢途径调控。中医药学正是具有这样的特点和优势,显示其理论体系的科学性与合理性。中医从整体出发,辨证施治,调和阴阳,维持机体内外环境的协调统一。方剂是实施对疾病调控的主要形式,并强调随病情发展变化而随证加减的动态调控,这是当代医学所追求的目标。

生物温敏性水凝胶的研究

采用明胶和N 异丙基丙烯酰胺 (NIPAM )为原料 ,制备了配比不同的明胶 /聚N 异丙基丙烯酰胺 (Gel/PNIPAM)水凝胶系列 ,研究了 pH值、温度对水凝胶的溶胀度和溶胀速度的影响。结果表明 ,明胶 /PNIPAM水凝胶对pH值、温度有明显的响应性 ,且随着组分中NIPAM配比的增加 ,水凝胶的温敏性明显增加 ;对水凝胶的溶胀动力学研究表明 ,体系配比对溶胀的影响与最低溶液临界温度 (LCST)有关 ,当温度大于LCST时 ,溶胀速度及溶胀度随明胶含量的增加而增加 ,当温度低于LCST且配比为 1/ 1(质量比 )时 。

Molecular Biological Mechanisms of Yuan Zhi Powder in the Treatment of Alzheimer's Disease: an Analysis Based on Network Pharmacology

Objective To predict the main active ingredients,potential targets and molecular mechanisms of Yuan Zhi powder in treatment of dementia by using network pharmacology.Methods A database of chemical constituents of Yuan Zhi powder was constructed by using databases and literatures.Potential targets were predicted by reverse molecular docking,and then a component-target network was constructed.The target network of Alzheimer's disease(AD)was mapped and analyzed to obtain the“active ingredient-AD target”network.The key targets were screened through network analysis.Finally,the rationality of the prediction was analyzed by comparing with the target reported in the literatures.Results There were180chemical constituents acting on the AD target,and the targets included three key targets(cyclooxygenase-2,muscarinic acetylcholine receptor M1,and muscarinic acetylcholine receptor M2)and an important target(acetylcholine esterase).Alzheimer's disease may be treated by regulating the activity of acetylcholine receptors and the binding toβ-amyloid protein,and its biological process may be concentrated in the acetylcholine receptor signal pathway,negative regulation of synaptic transmission and so on.Conclusion The fact that Yuan Zhi powder can treat AD is consistent with the characteristics of multi-components-multitargets-multiple pathways of traditional Chinese medicine.The important targets obtained from network analysis have a large proportion in literature research,so network analysis have some rationality.

Mechanism Prediction of Monotropein for the Treatment of Colorectal Cancer by Network Pharmacology Analysis

Objective To discover the pharmacological mechanisms of monotropein in colorectal cancer by network pharmacology methods.Methods The main-candidate-target network was constructed by the prediction of targets of monotropein, collection of therapeutic targets of colorectal cancer drugs, and construction of the target network and layers of screening. The data were interpreted by pathway enrichment and target score calculation.Results This study:(1) Demonstrated the potential of monotropein to be a multi-target drug against colorectal cancer using a computational approach;(2) Discovered 10 candidate targets of monotropein, among which protein kinase B(AKT1)exhibited the highest relevance and importance to colorectal cancer and proto-oncogene tyrosine-protein kinase Src(SRC),Bruton’s tyrosine kinase(BTK), and heat shock protein HSP 90-alpha(HSP90 AA1) also exhibited high relevance;(3) Observed 32 possible pathways related to the effects of monotropein on colorectal cancer, which might explain the mechanism of its action;and(4) Established a method to assess the importance of targets in the network.Conclusions This study offered clues for the mechanism of the bioactivities of monotropein against colorectal cancer by network analysis. Monotropein has the potential to be a multi-target drug against colorectal cancer, which lays the foundation for its clinical applications and further study.

Network pharmacology： an important breakthrough in traditional Chinese medicine research

Objective： To study the relationship between traditional Chinese medicine （TCM） research and network pharmacology. Methods： Discuss the common features of TCM and network pharmacology through the analysis of the characteristics of TCM, the background of network pharmacology, so as better interpretation of TCM and in-depth understanding of TCM research and network pharmacology. Results： Multicomponent and multitarget characteristics of TCM as same as the study thought of network pharmacology. Network pharmacology breaks through the research model of linear and coincides with the complexity of TCM, provides technical support for rational design of TCM formulae, both and a new way in the research of TCM. It becomes a new strategy for modern TCM research. Conclusion： Network pharmacology is an important breakthrough in TCM research, its research promote modernization and internationalization process of TCM conduce to the research and development of TCM and have important significance for the integration of Chinese and Western medicine.

Potential Targets and Molecular Mechanism of Quercetin Against Knee Osteoarthritis

Objective The objective of this study was to clarify the potential mechanism of quercetin against knee osteoarthritis(KOA)based on network pharmacology and molecular docking.Methods The targets of quercetin were predicted by PubChem and Swiss Target Prediction databases,and the targets of KOA were obtained by DisGeNET,OMIM,and GeneCards databases.Then,the targets of quercetin and KOA were intersected to find the potential targets of quercetin against KOA.The protein–protein interaction network was constructed through the STRING database,and the core targets were screened.Gene ontology(GO)functions enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using DAVID database.The drug–target–pathway–disease network was constructed by Cytoscape software,and the molecular docking verification was performed by Vina.Results There were 49 potential targets for quercetin against KOA,including 10 core targets.GO functions enrichment analysis showed that the biological process of quercetin against KOA mainly involved the negative regulation of apoptotic process,collagen catabolic process,and extracellular matrix disassembly.KEGG pathway enrichment analysis showed that quercetin against KOA was closely related to PI3K-Akt signaling pathway,Rap 1 signaling pathway,FoxO signaling pathway,Ras signaling pathway,TNF signaling pathway,and ErbB signaling pathway.The results of molecular docking showed that the binding energies between ligand and receptors were less than−5 kcal·mol−1.Conclusions The molecular mechanism of quercetin against KOA involves many targets and pathways,which can regulate the proliferation and apoptosis of chondrocytes,degradation of extracellular matrix,and inflammatory reaction.Quercetin can stably bind to the active pockets of core target proteins,thereby exerting the effect against KOA.