RESUMO
Background: There is a lack of effective drugs for the treatment of coronary heart disease (CHD). Sedum aizoon L (SL) has multiple effects, and there is no report on CHD in SL at present. The aim of this study is to explore the mechanisms of action of SL in the treatment of CHD based on network pharmacology and molecular docking technology. Methods: The targets and active ingredients of SL were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and CHD-related targets were obtained by searching GeneCards and DisGeNet databases. The intersection of LS active ingredient targets and CHD targets was used to construct a "drug-ingredient-disease-target" network using the Cytoscape software. The STRING database was used to construct a protein-protein interaction (PPI) network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Key targets and core active ingredients were selected and molecular docking was performed using the AutoDock software. Results: According to the predicted results, a total of 134 corresponding target genes for LS, 12 active components, 1,704 CHD-related targets, and 52 intersecting targets were obtained. GO function and KEGG pathway analysis showed that the key targets were involved with signal transducer and activator of transcription 3 (STAT3), tumor protein p53 (TP53), and vascular endothelial growth factor A (VEGFA). The molecular docking results showed that the key targets bound to the important active ingredients in a stable conformation. The core active ingredients of LS in the treatment of CHD were determined to be ursolic acid, myricetin, and beta-sitosterol. Conclusions: SL may act on targets such as STAT3, TP53, and VEGFA through tumor necrosis factor (TNF) signaling pathway, interleukin 17A (IL-17A) signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and other related pathways, thereby playing a role in preventing and treating CHD.
RESUMO
OBJECTIVE: Hypothyroidism is a disease with symptoms of collective metabolic dysfunction and systemic dysfunction due to the lack of serum thyroid hormones caused by various reasons. GLUT4 is over-expressed in monocytes of patients with hyperthyroidism, there are also studies suggesting that there is a certain regulatory relationship of GLUT1 and GLUT4 with thyroid function. This study is aimed to explore the correlation of glucose transporter 1 (GLUT1) and GLUT4 with prognosis of patients with hypothyroidism and cardiac insufficiency. METHODS: From July 2016 to October 2019, totally 116 patients with cardiac insufficiency complicated with subclinical hypothyroidism treated in our hospital were enrolled in the research group (RG), and 110 patients with cardiac insufficiency but normal thyroid function were enrolled in the control group (CG). Serum GLUT1, GLUT4, free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were detected, and the correlation between them was analyzed. Then the predictive value and risk factors of GLUT1 and GLUT4 for poor prognosis of hypothyroidism complicated with cardiac insufficiency were analyzed. RESULTS: The expression levels of GLUT1, GLUT4, FT3 and FT4 in serum of patients in RG was notably lower than that in CG, and TSH expression was remarkably higher than those in CG (P<0.05). In RG, GLUT1 and GLUT4 expression levels were positively correlated with FT3 and FT4 expression (P<0.05), but negatively correlated with TSH expression (P<0.05). ROC of GLUT1 and GLUT4 in RG in predicting poor prognosis of patients was over 0.8. Low expression of GLUT1 and GLUT4 and diabetes were independent risk factors for poor prognosis in patients with hypothyroidism complicated with cardiac insufficiency. CONCLUSION: GLUT1 and GLUT4 expression levels were significantly decreased in serum of patients with hypothyroidism complicated with cardiac insufficiency. Both of them have high predictive value for poor prognosis of patients, and are independent risk factors for poor prognosis of patients.