Identification of traditional Chinese drugs containing active ingredients for treating myocardial infarction and analysis of their therapeutic mechanisms by network pharmacology and molecular docking / 南方医科大学学报

OBJECTIVE@#To identify traditional Chinese drugs that contain active ingredients for treatment of myocardial infarction (MI) and explore their therapeutic mechanisms using network pharmacology and molecular docking technology.@*METHODS@#The TCMSP database was used for screening the traditional Chinese drugs containing active ingredients for treating MI, and the related targets of MI and the candidate drugs were obtained from Genecards, OMIM, PharmGkb and PharmMapper databases. The common target network of the drug targets and disease targets was established using Venny2.1.0 software. GO and KEGG signal pathway enrichment analysis of the common targets was performed, and the protein-protein interaction (PPI) network was constructed for the targets. The targets in the PPI network were analyzed to identify the key targets, for which GO and KEGG pathway enrichment analyses were performed. Molecular docking was performed for the candidate ingredients and the key targets, and a total score ≥6 was used as the criteria for screening the therapeutic ingredients and their docking binding with key targets was verified. A human umbilical vein endothelial cell (HUVEC) model of oxygen-glucose deprivation (OGD) was used to validate the candidate ingredients and the key therapeutic targets for MI by Western blotting.@*RESULTS@#Our analysis identified Salvia miltiorrhiza and Dalbergiae odoriferae as the candidate drugs rich in active ingredients for treatment of MI. These ingredients involved 16 key therapeutic targets for MI, which participated in such biological processes as inflammatory response, angiogenesis, energy metabolism and oxidative stress and the pathways including HIF-1, VEGF, and TNF pathways. Sclareol and PTGS2 in Salvia miltiorrhiza and formononetin and KDR in Dalbergiae odoriferae all had high docking total scores. Western blotting showed that at medium and high doses, sclareol significantly inhibited PTGS2 expression and formononetin promoted KDR expressions in the cell models in a dose-dependent manner (P < 0.05).@*CONCLUSION@#Both Salvia miltiorrhiza and Dalbergiae odoriferae have good therapeutic effects on MI. Sclareol in Salvia miltiorrhiza and formononetin in Dalbergiae odoriferae regulate the expressions of KDR and PTGS2, respectively, to modulate the inflammatory response, angiogenesis, oxidative stress and energy metabolism and thus produce myocardial protective effects.

Cytotoxicity and apoptosis induction in human HepG2 hepatoma cells by decabromodiphenyl ethane / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the toxic effects of decabromodiphenyl ethane (DBDPE), used as an alternative to decabromodiphenyl ether in vitro.</p><p><b>METHODS</b>HepG2 cells were cultured in the presence of DBDPE at various concentrations (3.125-100.0 mg/L) for 24, 48, and 72 h respectively and the toxic effect of DBDPE was studied.</p><p><b>RESULTS</b>As evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays and nuclear morphological changes, DBDPE inhibited HepG2 viability in a time- and dose-dependent manner within a range of 12.5 mg/L to 100 mg/L and for 48 h and 72 h. Induction of apoptosis was detected at 12.5-100 mg/L at 48 h and 72 h by propidium iodide staining, accompanied with overproduction of reactive oxygen species (ROS). Furthermore, N-acetyl-L-cysteine, a widely used ROS scavenger, significantly reduced DBDPE-induced ROS levels and increased HepG2 cells viability.</p><p><b>CONCLUSION</b>DBDPE has cytotoxic and anti-proliferation effect and can induce apoptosis in which ROS plays an important role.</p>

Abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model induced by high fat diet / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To establish abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model fed with high fat diet. And then to investigate the pathological characteristics of this quail model.</p><p><b>METHODS</b>Thirty Longcheng quails were randomly divided into two groups: control group and model group (n=15). The control group quails were fed with normal diet and model group quails were fed with high fat diet for 14 days. After a 12-hour overnight fast, liver and abdominal fat at euthanasia as well as serum were collected. The levels of serum uric acid, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride, free fatty acid (FFA), and blood glucose were assayed. The activity changes of adenosine deaminase (ADA), xanthine oxidase (XOD), lipoprotein lipase (LPL), hepatic lipase (HL), and fatty acid synthetase (FAS) were analyzed.</p><p><b>RESULTS</b>Compared with control group, the abdominal fat content (0.74+/-0.63 vs. 1.36+/-0.65 g, P<0.05) and abdominal fat index (0.44%+/-0.30% vs. 0.85%+/-0.30%, P<0.01) as well as live lipid index (3.61%+/-0.65% vs. 11.33%+/-2.14%, P<0.01) in model group significantly increased; the levels of serum uric acid (210.61+/-94.76 vs. 304.25+/-141.94 micromol/L, P<0.05), total cholesterol (4.20+/-0.51 vs. 20.10+/-11.25 mmol/L, P<0.01), LDL-C (1.16+/-0.29 vs. 10.78+/-6.48 mmol/L, P<0.01), and FFA (0.39+/-0.14 vs. 0.55+/-0.15 mmol/L, P<0.01) in model group significantly increased; HDL-C (5.85+/-0.95 vs. 4.14+/-2.03 mmol/L, P<0.05) significantly decreased; the levels of triglyceride and blood glucose had no significant changes (P>0.05); the activities of ADA (9.71+/-3.05 vs. 17.19+/-5.10 U/ml, P<0.01) and XOD (10.58+/-6.88 vs. 19.22+/-9.44 U/L, P<0.01) in model group significantly increased; and FAS, LPL, HL had no significant changes (P>0.05).</p><p><b>CONCLUSIONS</b>High fat diet can induce abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model. The changes of uric acid and lipid metabolic enzyme activities may be the pathological mechanism of abdominal fat accumulation with hyperuricemia and hypercholesterolemia.</p>