Background Atherosclerosis (AS), one of the leading causes of deaths and disabilities, is a kind of vascular disease of lipid disorders and chronic inflammation. Guanxinping (GXP) has been administrated in the treatment of AS for nearly 20 years with satisfying clinical response. This study aimed to explore its underlying mechanisms of anti-atherosclerotic effect in AS. Methods Male ApoE−/− mice were randomized into five groups and fed with either standard diet (control group, CON) or high-fat diet (HFD) for 12 weeks. HFD mice were further divided randomly and either fed continually with HFD as a model group, or atorvastatin (ATO), or low-dose GXP (LGXP), or high-dose GXP (HGXP). After 12 weeks, the body weight, serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) were detected. Moreover, serum inflammation cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) concentrations were measured. The structure of aortic tissues was examined by hematoxylin-eosin staining. The mRNA expression of TNF-α, IL-6, and IL-1β were assessed by qPCR. The protein expressions of ICAM-1, VCAM-1, MCP-1, IL-6, IL-1β, p38MAPK, ERK1/2, JNK, IκB-α, and NF-κBp65 in the aorta were also detected. Results GXP treatment reduced serum TG, TC, and LDL-c levels in ApoE−/− mice. Moreover, GXP reduced lipid accumulation in the aorta of ApoE−/− mice, induced by HFD. Furthermore, GXP ameliorated the aorta morphological damage and reduced the serum TNF-α, IL-6, and IL-1β levels. GXP also attenuated the protein expression of ICAM-1, VCAM-1, MCP-1, IL-6, IL-1β, p38MAPK, ERK1/2, JNK, and NF-κBp65, whereas it increased the IκBα level in aortic tissues of ApoE−/− mice. Conclusions Our results show that GXP could ameliorate atherosclerosis, which is mediated by inhibition of the MAPK/NF-κB signaling pathway in ApoE−/− mice. This study provides evidence that GXP might be a promising drug for the treatment of AS.
The traditional Chinese medicine (TCM) formula, Sheng Huang Chong Ji (SHCJ) is largely applied for treating Alzheimer’s disease (AD), but not much is known regarding its active compounds, molecular targets, and mechanism of action. The current study aimed to predict the potential molecular mechanism of SHCJ against AD based on network pharmacology combined with in vitro validation. Using public databases, SHCJ’s active compounds, their potential targets, and AD-related genes were screened, while Cytoscape Version 3.7.2 was used to build protein–protein interaction (PPI) and compound-disease-target (C-D-T) networks. Analysis of enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) terms was then carried out in R 4.0.2, including associated packages. Subsequently, molecular docking analysis was performed with AutoDock Vina 1.1.2, with intro experiments involving SH-SY5Y cells used to further investigate the mechanism of SHCJ against AD. Finally, a total of 56 active compounds of SHCJ and 192 SHCJ-AD-related targets were identified. Quercetin was identified as the top potential candidate agent. HSP90AA1, AKT1, and MAPK1 represent potential therapeutic targets. The PI3K-Akt signaling pathway potentially represents a core one mediating the effects of SHCJ against AD. Additionally, molecular docking analysis indicated that quercetin could combine well with AKT1 and multiple apoptosis-related target genes. During cell experiments, a significant increase in cell viability along with a decrease in Aβ25-35-induced apoptosis was observed after treatment with SHCJ. Furthermore, SHCJ significantly increased the phosphorylation of PI3K and Akt while reversing Aβ25-35-induced apoptosis-related protein expression downregulation.
Background: Observational studies have suggested associations between iron status and myocardial infarction (MI). However, it’s role as a risk factor or as a subeffect because of myocardial infarction is uncertain. Methods: We performed a literature search of genome-wide studies that evaluate iron status. We used a two-sample Mendelian randomization approach to evaluate the causality of iron status on myocardial infarction risk, using 2 cohorts: GIS (n=23,986) and UK Biobank(n=361,194). The two-sample MR study was conducted to estimate causal relationship between iron status and MI, with the inverse-variance weighted (IVW)method, weighted-median method. Moreover, MR-Egger regression, MR-PRESSO and leave-one-out analysis were performed to evaluate the potential pleiotropy effect. Results: Genome-wide association studies of iron status were evaluated. No associations were found in relation to myocardial infarction: iron [odds ratio(OR)=1.03[95% confidence interval CI,0.79-1.35];p-value=8.09×10−1], ferritin(OR=0.99[95% CI, 0.99-1.00];p-value=3.62×10−1), transferrin(OR =0.99[95% CI, 0.99-1.00];p-value=5.98×10−1), transferrin saturation(OR =0.99[95% CI, 0.99-1.00];p-value=4.55×10−1). MR-Egger, MR-PRESSO, and leave-one-out analysis did not indicate horizontal pleiotropy. Conclusion: Our MR study suggested that genetically predicted iron status was not causally associated with MI among the European populations.
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