Bioinformatics Forecast On The Molecular Mechanisms For The Treatment Of Coronary Heart Disease By The Common Drug Pairs Of Invigorating Qi, Promoting Blood Circulation And Blood-breaking Drugs

Objective1. To explore the regularities of common syndrome and Chinese herbal medicines (CHMs) on CHD.2. To forecast the molecular mechanisms of CHD treatment by the common drug pairs of invigorating qi, promoting blood circulation and blood-breaking drugs.MethodsThe data set on CHD was downloaded from Chinese BioMedical literature database. The regularities of traditional Chinese medicine (TCM) syndrome and CHMs on CHD were mined out by data slicing algorithm based on algorithms of discrete derivative, and key words directed text mining. The results were demonstrated with tables and networks, and then the main TCM syndrome of CHD and its corresponding CHMs could be obtained. CHMs which were strongly associated with the top TCM syndrome were selected for the study and some CHMs were recruited by manual analysis method. Through retrieved PubChem, human target proteins of the CHMs were obtained. Meanwhile, CHD genes were got through PubMed "Gene" database. Then the proteins and genes were imported into IPA platform respectively to get the corresponding networks, pathways and molecules etc. by compared and analyzed these networks, pathways, molecules etc., the molecular mechanisms for the treatment of CHD could be explored and forecasted.Results 1. Qi deficiency and blood stasis was the main TCM syndrome of CHD found with text mining. CHMs such as astragalus, ginseng, salvia miltiorrhiza and notoginseng were intimately associated with each other and they were also often used as the pairs of invigorating qi and promoting blood circulation for treatment of CHD with qi deficiency and blood stasis syndrome. These four CHMs plus blood-breaking drugs rhizoma sparganii and rhizoma curcumae by manual analysis method were seclected for this study to explored the molecular mechanisms for the treatment of CHD.2. Altogether there were12common molecules between CHD gene networks and three drug pairs networks found with bioinformatics analysis. And the target molecules of drug pairs such as CYP3A4, HIF1A, ESR1, ALB, MMP2, PPARD, PLA2G7, YP2C19, ESR2, PPARA, PPARG,OPRM1were included.3. There were certain regularities between CHD pathways and three drug pairs pathways discovered. For example, drug pairs of invigorating qi and promoting blood circulation had a high correlation with Cardiovascular Singnaling; while invigorating qi drug pairs had a high correlation with Cytokine Singnaling and Cellular Growth, Proliferation and Development; and drug pairs of promoting blood circulation had a high correlation with Nuclear Receptor Signaling; drug pairs of promoting blood circulation and blood-breaking drugs had a high correlation with Metabolic Pathway.4. Altogether there were12common molecules between CHD gene pathways and three drug pairs pathways found. And the target molecules of drug pairs such as CYP3A4, HIF1A, ESR1, ALB, MMP2, PPARD, PLA2G7, YP2C19, ESR2, PPARA, PPARG, OPRM1were included. Among these common targets of networks and pathways, HIF1A, ESR1and CYP3A4were the common targets of three drug pairs; PPARD and PLA2G7were the common targets of drug pairs of invigorating qi and promoting blood circulation; OPRM1was the common targests of promoting blood circulation and blood-breaking drug pairs; MMP2and ALB were the targets of invigorating qi drugs pairs; ESR2, CYP2C19, PPARG and PPARA were the targets of promoting blood circulation drugs pairs.Conelusions1. Qi deficiency and blood stasis was the main TCM syndrome of CHD which reflected the basic pathogenesis of CHD in TCM. Astragalus, in combination with ginseng, salvia miltiorrhiza and notoginseng, were used as the common drug pairs for treatment of CHD in TCM. The results of text mining reflected the clinical diagnosis and treatment of CHD in TCM.2. Altogether there were12common targets such as HIFIA、ESR1、CYP3A4in the biological networks and pathways between CHD gene and three drug pairs. Three drug pairs through these targets regulate CHD pathways, networks may be the mechanisms of the drug pairs for the treatment of CHD, which also reflect the drug pairs may regulate CHD through multi-targets and multi-pathways.3. There were certain regularities between CHD pathways and three drug pairs pathways, and these regularities reflect characteristics of the three drug pairs on the impact of CHD. Three drug pairs had something in common for affecting CHD. For example,three of them could regulate the pathways such as Hypoxia Signaling in Cardiovascular System, HIF1α Signaling, VEGF Signaling through HIF1A. However, three of them had something different, for example, salvia miltiorrhiza and notoginseng, rhizoma sparganii and rhizoma curcumae could regulate G-Protein Coupled Receptor Signaling through OPRM1, and astragalus and ginseng could regulate the pathways such as HIF1α Signaling and IL-8Signaling through MMP2. The similarities and differences between the durg pairs reflect the molecular mechanisms of CHD treatment by the durg pairs alone or together, which provide the theoretical basis of molecular mechanisms for CHD treatment by the durg pairs alone or together, and also provide the molecular theoretical thinking for similarities and differences of efficacy and indications based on the theory of traditional Chinese medicine between the durg pairs.4. It is an effective approach to explore and forecast the molecular network mechanisms of disease in TCM through combined text mining technology with bioinformatics analysis.