Background and Purpose: Two Chinese herbal medicines Huang Qi (HQ, Astragalus mongholicus) and Dan Shen (DS, Salvia miltiorrhiza) are often combined to treat coronary heart disease (CHD). The purpose of this study was to identify the underlying synergistic effects and mechanisms of HQ and DS against CHD. Methods: The active components and targets of HQ and DS, CHD-related genes, and the biological progression were analysed by network pharmacology. The myocardial infarction (MI) rat model was established by ligating the left anterior descending coronary artery. Cardiac function was detected by ultrasonic electrocardiography. The MI size, fibrosis, cardiac hypertrophy, lipid metabolism, blood viscosity, and coagulation indexes were analysed by histological staining or chemical methods, respectively. Results: A total of 170 shared and specific seed genes of HQ and DS against CHD were identified. The shared and specific biological processes of HQ and DS against CHD were obtained. The LVEF and LVFS values significantly increased, the myocardium infarct size and fibrosis significantly decreased, the values of lipid metabolism indexes and blood viscosity indexes significantly reduced in the HQ + DS treatment group vs HQ or DS single treatment (P < 0.05); the LVEDd, LVEDs, and the CSA values significantly reduced in HQ single and HQ + DS treatment groups vs MI group (P < 0.05); the coagulation index (APTT, PT, TT, and FIB) values decreased significantly in the DS single and HQ + DS treatment groups vs MI group (P < 0.05). Conclusion: In MI rats, HQ and DS exhibited synergistic effects on improving cardiac function, reducing MI size, fibrosis, regulating hyperlipidaemia, and maintaining circulatory system homeostasis; HQ had the specific advantage of alleviating cardiac remodelling; DS had the specific advantage of regulating hypercoagulability. This study revealed that HQ and DS not only exerted synergistic effects but also exhibited complementary effects on CHD.

Coronary heart disease (CHD) is a leading cause of death and disability worldwide. Huoxue Anxin Recipe (HAR) is a novel Chinese Herbal Medicine formula of that has been used to treat CHD for several decades. Our previous study found that HAR had anti-oxidative effects, and could promote myocardial angiogenesis and improve cardiac function following myocardial infarction (MI) in rats. However, the active compounds, potential targets, and biological processes related to HAR have not been systematically investigated. Here, network pharmacology and experimental validation were used to study the protective mechanisms of HAR against CHD. We identified 124 active components, 124 verified targets, and 111 predictive targets. A total of 1192 genes related to CHD were identified by cDNA microarray and database analysis. A total of 47 putative targets of HAR against CHD were identified, including 32 verified targets and 15 predictive targets. ClueGo enrichment analysis identified 49 biological processes involved in the anti-CHD effects of HAR. Among them, the negative regulation of blood coagulation and regulation of collagen biosynthetic process were experimentally validated. After constructing a protein-protein interaction network and clustering with MECODE and ClusterONE, 162 key proteins (from ClueGo and clustering) were used to construct an internal interaction network. Complement C3 (C3), Fibrinogen alpha (FGA), Fibrinogen gamma (FGG), interleukin-6 (IL6), and Apolipoprotein A1 (APOA1) were the top 5 hub proteins identified by cytoHubber analysis. HAR limited the concentrations of C3, FGA, FGG, and IL6 and increased APOA1 levels. The results indicated that HAR could down-regulate blood coagulation, regulate collagen biosynthesis, inhibit peroxidation and inflammation injury, and promote cholesterol efflux. HAR could be a potential source of novel and effective drugs for CHD.

Objective. Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas‐exchange impairment due to a severe inflammatory process known as cytokine storm. Xuebijing injection (hereinafter referred to as Xuebijing) is a patent drug that was used to treat ARDS or severe pneumonia (SP) in China. However, its efficacy and mechanism of actions remain unclear. In this study, we used meta‐analysis and network pharmacology to assess these traits of Xuebijing. Methods. We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases for randomized controlled trials (RCTs) that evaluated Xuebijing therapy for ARDS or SP. The outcomes were total mortality, intensive care unit (ICU) stay time, and TNF‐α and IL‐6 levels. We performed a meta‐analysis using RevMan 5.3 software. The putative targets, top 10 proteins, and possible pathway of Xuebinjing on ARDS were analyzed by network pharmacology. TNF‐α and IL‐6 were further docked with the six main active components of Xuebinjing using AutoDock 4.2.6 and PyMol 1.5.0.3 software. Results. Fifteen RCTs involving 2778 patients (13 ARDS and 2 SP) were included. Compared with the control, Xuebijing treatment significantly reduced the mortality rate (risk ratio, 0.64 (95% credible interval (CrI), 0.54–0.77)), reduced the ICU stay time (mean difference (MD), ‐4.51 (95% CrI, ‐4.97–‐4.06)), reduced the TNF‐α ((MD), ‐1.23 (95% CrI, ‐1.38–‐1.08)) and IL‐6 ((MD), ‐1.15 (95% CrI, ‐1.52–‐0.78)) levels. The 56 putative targets, top 10 proteins (MAPK1 (mitogen‐activated protein kinase 1), MAPK8 (mitogen‐activated protein kinase 8), RELA (transcription factor p65), NFKB1 (nuclear factor NF‐kappa‐B p105 subunit), JUN (transcription factor AP‐1), SRC (proto‐oncogene tyrosine‐protein kinase), TNF (tumor necrosis factor), HRAS (GTPase HRas), IL6 (interleukin‐6), and APP (amyloid‐beta A4 protein)), and possible pathways (Ret tyrosine kinase, IL2‐mediated signaling events, CD4+/CD8+ T cell‐related TCR signaling, p75(NTR)‐mediated signaling, CXCR4‐mediated signaling events, LPA receptor‐mediated events, IL12‐mediated signaling events, FAS (CD95) signaling pathway, and immune system) of Xuebinjing’s action on ARDS were obtained. The molecular docking results showed that all the six components of Xuebinjing docked with TNF‐α, and two components docked with IL‐6 got the binding energies lower than ‐5. Conclusion. Our results recommended Xuebijing treatment for patients with ARDS. Xuebijing has therapeutic effects on ARDS patients partly by regulating the immune cell/cytokine pathways and thus inhibiting the cytokine storm. TNF‐α is the cytokine both directly and indirectly inhibited by Xuebijing, and IL‐6 is the cytokine mainly indirectly inhibited by Xuebijing.

Background: Improving angiogenesis in the ischemic myocardium is a therapeutic strategy for preventing, reducing, and repairing myocardial injury of coronary artery disease (CAD). Panax notoginseng saponins (PNS) have been widely used in the clinical treatment of cardiovascular diseases, demonstrating excellent efficacy, and can potentially improve angiogenesis in the ischemic myocardium. However, the effects of PNS on angiogenesis and its underlying mechanism of action remain unclear. Purpose: In this study, we aimed to evaluate the role of PNS in improving angiogenesis after myocardial infarction (MI) and explain the mechanism of PNS in improving angiogenesis in CAD from an epigenetic perspective. Study Design: The MI rat model was established by ligating the left anterior descending coronary artery permanently. The in vitro model comprised hypoxic human coronary artery endothelial cells (HCEACs). The mice and cells were then treated with PNS. Methods: Blood tests, histomorphology, polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and MassARRAY targeted methylation detection analyses were conducted in vivo and in vitro to investigate the potential mechanisms of PNS. Results: Oral PNS significantly improved myocardial injury and activated angiogenesis in MI rats. DNA methylation analysis in vitro revealed that PNS decreased the hypermethylation of microRNA 200a (miR200a). PNS improved angiogenesis in hypoxic human coronary artery endothelial cells (HCEACs) by regulating the vascular endothelial growth factor (VEGF) pathway. Conclusion: Our research shows that PNS can improve angiogenesis in rats with MI and hypoxic HCEACs and affect the level of miR200a promoter methylation and miR200a and VEGF molecular pathways.