ABSTRACT
ObjectiveTo investigate the potential pharmacological mechanism of Xinmaikang tablets in the treatment of atherosclerosis cardiovascular disease by using network pharmacology and cell experimental validation. MethodThe components of Xinmaikang tablets were searched by BATMAN-TCM database and the active ingredients and potential targets were screened. The atherosclerosis related disease targets were searched in GeneCards and online mendelian inheritance in man（OMIM） disease databases. The therapeutic targets were obtained by mapping the intersection of the tablets and disease targets. Therapeutic targets were uploaded to STRING database to construct protein-protein interaction（PPI） network. Cytoscape software was used to create a "drug-active component-therapeutic target" network map， and a network topology algorithm was used to screen key action targets. David software was used for gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） function enrichment analysis. The key targets of drug therapy were validated by in vitro cell assay. ResultA total of 19 active ingredients， 132 potential targets and 4703 atherosclerotic disease-related target genes of Xinmaikang tablets were retrieved and screened， and 84 intersection targets were obtained. 3 key therapeutic targets of Xinmaikang tablets in the treatment of atherosclerotic diseases were screened， including Calmodulin 1（CALM1）， voltage-dependent L-type calcium channel subunit alpha-1C（CACNA1C） and Phosphatidylinositol 4，5-bisphosphate 3-kinase catalytic subunit alpha isoform（PIK3CA）. A total of 313 biological processes， 89 molecular functions and 53 cell components were obtained by GO enrichment. A total of 40 pathways were obtained from KEGG functional enrichment， including purine metabolism， renin secretion， CGMP/PKG signaling pathway and so on. In vitro cell experiment results verified that Xinmaikang tablets can up-regulate the expression of CALM1 and CACNA1C， down-regulate the expression of PIK3CA， so as to inhibit the activity of inflammatory response， and play a therapeutic role in atherosclerotic diseases. ConclusionXinmaikang tablets may treat atherosclerosis cardiovascular disease through betulin， methyleugenol and other compounds， through purine metabolism， renin secretion， cGMP/PKG signaling pathway and other pathways， which acts on CALM1， CACNA1C， PIK3CA and other targets.
ABSTRACT
<p><b>OBJECTIVES</b>To investigate the safety and efficacy of yangxinkang tablets in patients with chronic heart failure (CHF) and syndrome of qi and yin deficiency, blood stasis, and water retention.</p><p><b>METHODS</b>In a double-blinded, randomized, placebo-controlled, multicenter clinical trail, 228 patients with CHF New York Heart Association (NYHA) class II or III in stage C were assigned by randomized block method to two groups in a 1:1 ratio to undergo either conventional Western treatment or conventional treatment plus yangxinkang tablets for 4 weeks. The outcome measure were effect of cardiac function, Chinese medicine (CM) syndromes, scores of symptoms, signs, and quality of life measured by Minnesota Living with heart failure questionnaire (MLHFQ) before and after the treatment.</p><p><b>RESULTS</b>Totally 112 patients were analyzed in the treatment group and 109 in the control group. They were comparable in NYHA functional class, basic parameters and primary diseases before treatment. Cardiac function and CM syndromes were greatly ameliorated in both groups after treatment. Total effective rates of cardiac function and CM syndrome in the treatment group were significantly higher than those in the control group (P<0.05). Total symptom score and sign score in the treatment group decreased significantly after treatment (P<0.01), which were significantly lower than those in the control group (P<0.05). There were statistically significant differences in post-treatment scores of gasp, cough with phlegm, pulmonary rales and jugular vein engorgement between the two groups (P<0.05 or P<0.01). Three MLHFQ scores decreased significantly in both groups after treatment (P<0.01). Post-treatment total scale score and physical subscale score in the treatment group and the reduction of them showed statistically significant differences (P<0.05) as compared with the control group. There was no significant difference between the two groups in emotional subscale score and the reduction after treatment (P>0.05). There was no obvious adverse reaction in either group noted during the study.</p><p><b>CONCLUSIONS</b>Yangxinkang tablets were safe and efficacious in improving cardiac function, CM syndromes, symptoms, signs, and quality of life in patients with CHF class II or III in stage C on the base of conventional treatment.</p>