Metabonomic Strategy for the Evaluation of Chinese Medicine Salvia miltiorrhiza and Dalbergia odorifera Interfering with Myocardial Ischemia/Reperfusion Injury in Rats.

Extract of Salvia miltiorrhiza and Dalbergia Odorifera (SM-DOO) has been traditionally used for the prevention and treatment of cardiovascular diseases. However, information regarding the pharmacodyamic material basis and potential mechanism remain unknown. Male Sprague-Dawley rats were divided into four groups: Sham, Model, Diltiazem, and SM-DOO group, n = 6. Rats were pretreated with homologous drugs for 7 days, and then subjected to 30 minutes of ischemia followed by 180 minutes of reperfusion. Cardioprotection effects of SM-DOO on myocardial ischemia/reperfusion (MI/R) injury rats were examined by hemodynamics, infarct area, histopathology, biochemical indicators, and Western blot analysis. Metabonomics technology was further performed to evaluate the endogenous metabolites profiling systematically. According to the results of pattern recognition analysis, a clear separation of MI/R injury in the Model group and Sham group was achieved and SM-DOO pretreatment group was located much closer to the Sham group than the Model group, which was consistent with results of biochemistry and histopathological assay. Moreover, potential biomarkers were identified to elucidate the drug mechanism of SM-DOO, which may be related with pathways of energy metabolism, especially tricarboxylic acid (TCA) cycle (citric acid) and ß-oxidation of fatty acids (3-hydroxybutyric, palmitoleic acid, heptadecanoic acid, and arachidonic acid). In addition, the protein expressions of p-AMPK and p-ACC in the SM-DOO group were significantly elevated, while the levels of carnitine palmitoyl-CoA transferase-1 (CPT-1), p-PDK, and p-PDC were dramatically reduced by SM-DOO. In conclusion, SM-DOO pretreatment could ameliorate MI/R injury by intervening with energy metabolism, especially TCA cycle and ß-oxidation of fatty acids. This work showed that the metabonomics method combinate with conventional pharmacological methods is a promising tool in the efficacy and mechanism research of traditional Chinese medicines.

Differential gene expression profiles between two subtypes of ischemic stroke with blood stasis syndromes.

Ischemic stroke is a cerebrovascular thrombotic disease with high morbidity and mortality. Qi deficiency blood stasis (QDBS) and Yin deficiency blood stasis (YDBS) are the two major subtypes of ischemic stroke according to the theories of traditional Chinese medicine. This study was conducted to distinguish these two syndromes at transcriptomics level and explore the underlying mechanisms. Male rats were randomly divided into three groups: sham group, QDBS/MCAO group and YDBS/MCAO group. Morphological changes were assessed after 24 h of reperfusion. Microarray analysis with circulating mRNA was then performed to identify differential gene expression profile, gene ontology and pathway enrichment analyses were carried out to predict the gene function, gene co-expression and pathway networks were constructed to identify the hub biomarkers, which were further validated by western blotting and Tunel staining analysis. Three subsets of dysregulated genes were acquired, including 445 QDBS-specific genes, 490 YDBS-specific genes and 1676 blood stasis common genes. Our work reveals for the first time that T cell receptor, MAPK and apoptosis pathway were identified as the hub pathways based on the pathway networks, while Nfκb1, Egfr and Casp3 were recognized as the hub genes by co-expression networks. This research helps contribute to a clearer understanding of the pathological characteristics of ischemic stroke with QDBS and YDBS syndrome, the proposed biomarkers might provide insight into the accurate diagnose and proper treatment for ischemic stroke with blood stasis syndrome.