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.
Highlights
Shengmai injection (SMI), a traditional Chinese medicine (TCM) formula composed of Panax ginseng C.A.Mey., Ophiopogon japonicus (Thunb.) Ker Gawl., and Schisandra chinensis (Turcz.) Baill., is widely used in clinic for treating cardiovascular diseases in China
To confirm the cardioprotective effect of SMI on ischemia injury in rats, the histology analysis and myopathological enzymatic indicators detection of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and superoxide dismutase (SOD) in serum were performed before serum proteomic study
It is found that serum LDH and CK-MB levels significantly increased and the SOD level significantly decreased in rats after ISOinduced myocardial ischemia injury, while SMI pretreatment could significantly attenuate the changes of these enzymatic indicators (Figure 2B)
Summary
Shengmai injection (SMI), a traditional Chinese medicine (TCM) formula composed of Panax ginseng C.A.Mey., Ophiopogon japonicus (Thunb.) Ker Gawl., and Schisandra chinensis (Turcz.) Baill., is widely used in clinic for treating cardiovascular diseases in China. SMI’s favorable clinical applications have attracted great interests in pharmacological studies, especially for its cardioprotective effects It showed SMI protected cardiomyopathy by alleviating myocardial endoplasmic reticulum stress and caspase12–dependent apoptosis (Chen et al, 2015a), or inducing myocardial mitochondrial autophagy via caspase-3/beclin-1 axis (Cao et al, 2020). The related mechanism studies revealed SMI alleviated oxidative stress by activation of AKT and inhibition of ERK pathways (Zhu et al, 2019) and suppressed cardiomyocyte hypertrophy via activation of the AMPK signaling pathway (Li et al, 2019) All these studies focusing on SMI’s minority action targets and its comprehensive regulation mechanisms with the nature of multicomponent and multi-target are still poorly understood. It is still lacking reasonable and accessible biomarkers for SMI’s treatment in cardiovascular diseases
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