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And therefore, proteomics and metabolomics have been applied to explore SMI’s molecular mechanism. Systems biology methodologies, such as genomics, proteomics, and metabolomics, have showed significant advantages in studying the specific symptoms in TCM and the herbal formula’s comprehensive mechanism of action ( Cai et al., 2018 Jiang and Li, 2020).
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Moreover, it is still lacking reasonable and accessible biomarkers for SMI’s treatment in cardiovascular diseases.
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However, 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. In addition, 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). SMI prevented myocardial ischemia reperfusion injury by reducing myocardial apoptosis and enhancing vascular endothelial growth factor (VEGF)–related angiogenesis ( Lin et al., 2018). It showed SMI protected cardiomyopathy by alleviating myocardial endoplasmic reticulum stress and caspase-12–dependent apoptosis ( Chen et al., 2015a), or inducing myocardial mitochondrial autophagy via caspase-3/beclin-1 axis ( Cao et al., 2020). SMI’s favorable clinical applications have attracted great interests in pharmacological studies, especially for its cardioprotective effects. And recent meta-analysis also showed SMI add-on therapy increased efficacy for chemotherapy in patients with non–small cell lung cancer ( Duan et al., 2018) and the treatment of chronic obstructive pulmonary disease ( Huang et al., 2019). According to the systematic reviews and meta-analysis, compared with Western medicine alone, SMI adjuvant therapy significantly improved cardiac function of patients with intradialytic hypotension ( Chen et al., 2013) or chronic heart failure ( Wang et al., 2020). 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. 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. 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. control group, while back-regulated in SMI pretreatment + model vs. Furthermore, 10 common DEPs were found, and six of them were regulated in model vs. 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. 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.
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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. 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.