Investigation of cardiovascular protective effect of Shenmai injection by network pharmacology and pharmacological evaluation

Abstract

Background: Shenmai injection (SMI) has been used in the treatment of cardiovascular disease (CVD), such as heart failure, myocardial ischemia and coronary heart disease. It has been found to have efficacy on doxorubicin (DOX)induced cardiomyopathy. The aims of this study were to explore the underlying molecular mechanisms of SMI treatment on CVD by using network pharmacology and its protective effect on DOX-induced cardiotoxicity by in vitro and in vivo experiment based on network pharmacology prediction.Methods: Network pharmacology method was used to reveal the relationship between ingredient-target-disease and function-pathway of SMI on the treatment of CVD. Chemical ingredients of SMI were collected form TCMSP, BATMAN-TCM and HIT Database. Drugbank, DisGeNET and OMIM Database were used to obtain potential targets for CVD. Networks were visualized utilizing Cytoscape software, and the enrichment analysis was performed using IPA system. Finally, cardioprotective effects and predictive mechanism confirmation of SMI were investigated in H9c2 rat cardiomyocytes and DOX-injured C57BL/6 mice.Results: An ingredient-target-disease & function-pathway network demonstrated that 28 ingredients derived from SMI modulated 132 common targets shared by SMI and CVD. The analysis of diseases & functions, top pathways and upstream regulators indicated that the cardioprotective effects of SMI might be associated with 28 potential ingredients, which regulated the 132 targets in cardiovascular disease through regulation of G protein-coupled receptor signaling. In DOX-injured H9c2 cardiomyocytes, SMI increased cardiomyocytes viability, prevented cell apoptosis and increased PI3K and p-Akt expression. This protective effect was markedly weakened by PI3K inhibitor LY294002. In DOX-treated mice, SMI treatment improved cardiac function, including enhancement of ejection fraction and fractional shortening. Conclusions: Collectively, the protective effects of SMI on DOX-induced cardiotoxicity are possibly related to the activation of the PI3K/Akt pathway, as the downstream of G protein-coupled receptor signaling pathway.

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“…When used in combination with chemotherapy drugs, it has a synergistic effect and can reduce the side effects of chemotherapy drugs [ 59 ]. The main components of Shenmai injection are saponins, sugars, amino acids, flavonoids, lignans, organic acids, and other substances [ 60 ]. Shenmai can reduce the level of inflammatory factors, increase anti-inflammatory factors, and reduce the content of white blood cells, c-reactive protein, and procalcitonin when used for the adjuvant treatment of severe pneumonia.…”

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“…Traditional Chinese medicine has unique advantages in regulating oxidative stress and cell injury. Shenmai injections are a commonly used drug for myocardial protection in clinics, with confirmed efficacy [ 27 ]. Many studies have shown that Shenmai injection can alleviate myocardial cell damage caused by many factors, including ischemia-reperfusion, doxorubicin, and hydrogen peroxide.…”

LuQi Formula Regulates NLRP3 Inflammasome to Relieve Myocardial-Infarction-Induced Cardiac Remodeling in Mice

“…e heart was examined in the long-axis view at the papillary muscle level, and an M-mode echocardiogram of the mid ventricle was recorded. Cardiac function indices including LVEF, LVFS, LVIDd, and LVIDs were recorded [16]. Evidence-Based Complementary and Alternative Medicine 2.4.…”