| Based on the syndrome differentiation theory of traditional Chinese medicine, the TCM formula is the combination of several herbal medicines under the direction of the theory of principal, subordinate, adjuvent and guide. There are thousands and hundreds of compounds in one formula, several of them take responsibilities for curing diseases in a multi-target way. Additionally, there might be physical and chemical interactions during the manufacturing process of herbal medicine, which may produce various kinds of complex substances. Thus, the therapeutic mechanism of TCM formula must be very complicated as a result of its complex composition. Therefore, to explain the therapeutic mechanism of TCM using morden science technologies is always the main objectve of the modernization of traditonal Chinese medicine.Metabolomics is a newly developed strategy. It is’the quantitative measurement of the multi-parametric metabolic response of living systems to pathophysiological stimuli or genetic modifications’. Metabolomics is a new tool to holistically investigate metabolites in vivo responding to a disease process or drug therapy, which seasonably match the mechanism study of TCM.Shexiang Baoxin Pill (SBP), which consists of seven kinds of medicinal materials including Moschus, Radix Ginseng, Cortex cinnamomi, Styrax, Calculus Bovis, Venenum Bufonis and Borneolum Syntheticum, is a widely used TCM formula for the treatment of coronary heart diseases (CHD) in clinic for more than30years. Pharmacological research presented that SBP can improve the flow of coronary artery, decrease oxygen consume of cardiac muscle, slow down the heart rate, improve the function of constriction of left chamber, and enhance the function of the heart.. Simplified formula of TCM is based on the theory of traditional Chinese medicine, combined with the current developing method and technology, and consisted of active ingredients which take main responsibilities of a TCM formula. It is a new way to develope TCM new drugs. We have settled the composition of simplified formula of SBP (SFSBP) according to the results of our previous studies, which laid a foundation for the second development of SBP.In this study, the metabolomics method as well as the advanced LC-MS technique was applied to investigate the therapeutic mechanisms and protection effects of SFSBP and SBP on acute myocardial infraction (AMI) rats through animal experiment.Firstly, we investigate the therapeutic mechanism of SBP in treating MI rats through metabolomics strategy. Twenty seven biomarkers have been identified. These biomarkers mainly involved in oxidative injury, dysfunction of energy metabolism, dysfunction of amino acid metabolism and inflammation induced by AMI. The therapeutic mechanism of SBP mainly related to the inhibiting dysfunction of energy metabolism, oxidative injuryand inflammationinduced by AMI, while the therapeutic mechanism of the positive control medicine Polypill to inhibiting oxidative injury and inflammation of MI. Take a combination of results of Partial Least Squares Discriminant Analysis (PLS-DA) and regulation effects of identified biomarkers, it comes to a conclusion that the therapeutic effect of SBP was superior to Polypill. When compared the therapeutic effect of Polypill on MI with its’five constitutes mono-therapy groups (simvastatin, atenolol, ramipril, hydrochlorthiazide, and aspirin), both results of PLS-DA score plots and evaluation of biomarkers demonstrated that the therapeutic effect of Polypill was superior to mono-therapy groups (simvastatin, atenolol, ramipril, hydrochlorthiazide, and aspirin).when compared the therapeutic effect of SBP and SFSBP on AMI, we found that the therapeutic mechanism of SFSBP was mainly involved in regulating dysfunction of energy metabolism, oxidative injury and inflammation, which nearly as similar as SBP. Whereas, the PLS-DA score plot of SBP and SFSBP demonstrated that SBP group was closer to sham group than SFSBP, indicating that the therapeutic effect of SBP was superior to SFSBP. Additionally, both results of PLS-DA score plots and regulation of identified biomarkers showed that the therapeutic effect of SFSBP was better than its’constitutes components treated groups (muscone, cinamic acid, bufalin, ginsenoside Re, ginsenoside Rbl, cholic acid and broneol). Considering the fact that each mono-therapy treated groups was presented at a higher dose concentration than SFSBP treated group, it comes to a conclusion that the combination therapy strategy of SFSBP was indeed more efficient than mono-therapy groups and there might a synergistic effect.Secondly, we investigate the preventative effect of SBP, SFSBP and its’seven constitutes components on AMI rats through metabolomics technology. Twenty eight biomarkers have been identified, which mainly related to tryptophan metabolism and pyrimidine metabolism. The therapeutic effects of SBP and SFSBP were mainly on regulating biomarkers of tryptophan metabolism, and related to oxidative injury, dysfunction of platelet metabolism, hypertrophy, inflammation and dysfunction of energy metabolism. When evaluated reverse effect of different administered groups on identified biomarkers, we found that the regulation effect of SFSBP was mainly in inhibiting inflammation, oxidative injury and dysfunction of platelet metabolism induced by AMI, while the therapeutic effect of SBP was mainly involved in regulating hypertrophy, inflammation, oxidative injury and dysfunction of energy metabolism. Although the reverse effect of SBP and SFSBP treatments were almost the same, but the PLS-DA score plots showed that SBP treated group was closer to sham group, indicating that the reverse effect of SFSBP was inferior to SBP, more studies should be carried out to improve the composition of SFSBP. In addition, therapeutic effects of SFSBP and its’seven constitutes treated groups were also studied through integral analysis (PLS-DA) and evaluation of identified biomarkers (reverse effect of amount and degree of biomarkers), the results demonstrated that the reverse effect of SFSBP was superior to mono-therapy groups (muscone, cinamic acid, bufalin, ginsenoside Re, ginsenoside Rb1, cholic acid and broneol). Furthermore, considering the fact that each single-component treated groups was presented at a higher dose concentration than SFSBP treated group, indicating that there might a synergistic effect of combination therapy strategy of SFSBP. |
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