A Quantitative Serum Proteomic Analysis Helps to Explore the Comprehensive Mechanism and Identify Serum Biomarkers of Shengmai Injection’s Effect on Isoproterenol-Induced Myocardial Ischemia in Rats

Abstract

Shengmai injection (SMI), a traditional Chinese medicine formula with the nature of multicomponent and multi-target, has been widely used in clinic for treating cardiovascular diseases in China; however, its comprehensive mechanism of action remains unclear. In this study, a TMT-based quantitative serum proteomics was performed to explore SMI’s global mechanism and help identify serum biomarkers of its effect on isoproterenol (ISO)-induced myocardial ischemia rats. The results of TMT-based proteomic analysis identified 227, 100, and 228 differentially expressed proteins (DEPs) for the model compared to the control group, SMI pretreatment + model compared to the model group, and SMI pretreatment + model compared to the control group, respectively. Based on bioinformatics analyses of gene ontology (GO), KEGG pathways, and the protein-protein interaction (PPI) networks for the DEPs, it is concluded that the comprehensive mechanism of SMI’s effect on ISO-induced myocardial ischemia injury includes regulation of energy metabolism, reducing endothelial cell permeability, regulation of vessel and cardiac contractility, anti-inflammation, and prevention of cell apoptosis. Furthermore, 10 common DEPs were found, and six of them were regulated in model vs. control group, while back-regulated in SMI pretreatment + model vs. model group. Among them, three functional proteins of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Fas apoptotic inhibitory molecule 3 (FAIM3), and uncharacterized protein (M0R5J4), which were verified by the PRM analysis, might be the potential serum biomarkers on SMI’s effects. Overall, this serum proteomics of SMI not only provides insights into the comprehensive mechanism underlying SMI’s effects on ischemic heart disease but also helps identify serum biomarkers for directing SMI’s cardioprotective effects.

Integrated transcriptomic and proteomic analyses of plerocercoid and adult Spirometra mansoni reveal potential important pathways in the development of the medical tapeworm

“…According to GO enrichment analysis, among the DEPs in adults versus plerocercoids, the top three enriched BP (translation, glycolytic process and microtubule-based process), MF (ribosome, GTPase activity and ferric iron binding) and CC (ribosome, dynein complex and small ribosomal subunit) categories indicate that most belong to energy metabolism-related and genetic information processing proteins. These annotations cover functions that are important to parasite metabolism, lifestyle and survival [ 37 , 38 ], and they are also enriched in the annotated proteomes of other parasites, such as M. corti and T. ovis [ 23 , 39 ]. The COG pathway enrichment analysis showed that the largest three groups (36% of the DEPs) were associated with "general function prediction only", "translation, ribosomal structure and biogenesis" and "posttranslation modification, protein turnover, chaperones", such as serine/threonine protein phosphatase, arginyl-tRNA synthetase and glutathione transferase.…”

[8]‐Gingerol exerts anti‐myocardial ischemic effects in rats via modulation of the MAPK signaling pathway and L‐type Ca2+ channels

“… 31 , 32 The ISO‐induced MI model was often recognized as a ubiquitous model for evaluating cardioprotective drugs. 33 , 34 , 35 , 36 High‐dose subcutaneous injection of ISO can cause a significant reduction in the blood and oxygen supplies to the myocardium, which is responsible for serious damage to the structure and the functional changes seen on ECGs, and eventually leads to apoptosis and necrosis of myocardial cells. 37 It is similar to the changes caused by human MI.…”

Classic mechanisms and experimental models for the anti‐inflammatory effect of traditional Chinese medicine

“…In fact, due to the complexity of Chinese medicine and the inter‐relationship of signaling pathways, TCM, especially Chinese medicine preparations, may affect most of the signaling pathways. Many outstanding studies using omics technology such as transcriptomics, 52 proteomics 53 and metabolomics have revealed the mechanisms of the anti‐inflammatory effects of TCM 54 and show that it is possible that multiple pathways may be involved in these effects.…”