RESUMEN
BACKGROUND: Every year, approximately 17 million people worldwide die due to coronary heart disease, with China ranking second in terms of the death toll. Myocardial ischemia-reperfusion injury (MIRI) significantly influences cardiac function and prognosis in cardiac surgery patients. Jiawei Danshen Decoction (JWDSD) is a traditional Chinese herbal prescription that has been used clinically for many years in China to treat MIRI. The underlying molecular mechanisms, however, remain unknown. To investigate the proteomic changes in myocardial tissue of rats given JWDSD for MIRI therapy-based proteomics. METHODS: MIRI rat model was created by ligating/releasing the left anterior descending coronary artery. For seven days, the drugs were administered twice daily. The model was created following the last drug administration. JWDSD's efficacy in improving MIRI was evaluated using biochemical markers and cardiac histology. Tandem mass tag-based quantitative proteomics (TMT) technology was also used to detect proteins in the extracted heart tissue. To analyze differentially expressed proteins (DEPs), bioinformatics analysis, including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways, were employed. Furthermore, western blotting confirmed the potential targets regulated by JWDSD. RESULTS: The histopathologic characteristics and biochemical data showed JWDSD's protective effects on MIRI rats. A total of 4549 proteins were identified with FDR (false discovery rate) ≤1%. Twenty overlapping were identified (162 DEPs and 45 DEPs in Model/Control or JWDSD/Model group, respectively). Of these DEPs, 16 were regulated by JWDSD. GO analysis provided a summary of the deregulated protein expression in the categories of biological process (BP), cell component (CC), and molecular function (MF). KEGG enrichment analysis revealed that the signaling pathways of neutrophil extracellular trap formation, RNA polymerase, serotonergic synapse, and linoleic acid metabolism are all closely related to JWDSD effects in MIRI rats. Furthermore, T-cell lymphoma invasion and metastasis 1 (TIAM1) was validated using western blotting, and the results were consistent with proteomics data. CONCLUSIONS: Our study suggests that JWDSD may exert therapeutic effects through multi-pathways regulation in MIRI treatment. This work may provide proteomics clues for continuing research on JWDSD in treating MIRI.
RESUMEN
yeyachun and danshen exist as Chinese patent medicine, Xuemai Tong, and are clearly effective at alleviating liver fibrosis (LF). Previous studies have indicated that triterpenoids from yeyachun (EFT), and phenolic acids from danshen (SMP) are effective in the treatment of LF. The regulation of intestinal flora is an effective method for treating LF. The aim of this study was to investigate the effect of a mixture of EFT and SMP on carbon tetrachloride (CCl4) induced LF. Our results showed the mixture significantly decreased liver damage and fibrosis index, and maintained liver tissue composition, compared to the model group. Moreover, the imbalance of symptoms of intestinal flora was improved. The mixture also caused changes to metabolites of gut flora. Furthermore, the expression of CD68 in liver tissues from the treated groups was significantly decreased when compared to the model group. However, no significant difference was observed from microstructure of gut tissues and LPS concentrations in the serum between mixture treated mice and model mice. This study suggests that the mixture of EFT and SMP had a significant effect on CCl4 induced LF, and the mechanism of this action, at least in part, involved the regulation of intestinal flora and their metabolites.