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.

Mechanism of Sinitang against Myocardial Ischemia-reperfusion Injury： Prediction Based on Network Pharmacology and Verification by Cellular Experiments / 中国实验方剂学杂志

ObjectiveTo predict the mechanism of Sinitang in treating myocardial ischemia-reperfusion injury （MI/RI） based on network pharmacology and verify the prediction results by cellular experiments. MethodThe traditional Chinese medicine system pharmacology database and analysis platform （TCMSP） was employed for retrieval of the main components and potential targets of Sinitang. Online Mendelian Inheritance in Man （OMIM） and GeneCards were employed to obtain the targets of Sinitang in treating MI/RI. STRING was employed to construct the protein-protein interaction （PPI） network， and DAVID to perform gene ontology （GO） annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment. Finally， cellular experiments were carried out to verify the predicted anti-MI/RI mechanism of Sinitang. ResultA total of 105 active ingredients and 234 targets of Sinitang were screened out， among which 116 targets were predicted to be involved in the treatment of MI/RI. The GO annotation gave 587 entries， including 417 biological process entries， 101 cell component entries， and 69 molecular function entries. The KEGG analysis enriched 125 signaling pathways， involving vascular endothelial growth factor （VEGF）， phosphoinositide 3-kinase/protein kinase B （PI3K/Akt）， forkhead box transcription factor O （FoxO）， hypoxia-inducible factor-1 （HIF-1） apoptosis and other signaling pathways. The results of cell viability assay showed that Sinitang increased the survival rate of H9C2 cells damaged by hypoxia/reoxygenation （H/R）. Sinitang decreased the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and creatine kinase-MB （CK-MB） in H9C2 cells damaged by H/R. The results of flow cytometry demonstrated that Sinitang decreased the apoptosis rate of H9C2 cells damaged by H/R. Western blot showed that Sinitang down-regulated the expression of Bcl-2 related X protein （Bax） and up-regulated that of B-cell lymphoma-2 （Bcl-2） in H/R-injured H9C2 cells. ConclusionSinitang treats MI/RI in a multi-target and multi-pathway manner， which involves the signaling pathways associated with apoptosis.

Research Progress on Hepatotoxicity Mechanism and Attenuation Methods of Psoraleae Fructus / 中国实验方剂学杂志

Psoraleae Fructus is the dried and mature fruit of the legume Psoralea corylifolia. It is warm in nature， pungent and bitter in flavor， and attributive to the kidney and spleen meridians. Its main effect include warming the kidney and assisting Yang， absorbing Qi and relieving asthma， warming the spleen and relieving diarrhea， etc.， and it also can for external use of eliminating wind and freckle. Clinically， Psoraleae Fructus is mainly used for the treatment of impotence due to kidney deficiency， soreness of waist and knees， vitiligo， etc. The existing studies have shown that Psoraleae Fructus has a variety of pharmacological effect， such as anti-tumor， anti-oxidant， anti-bacterial， anti-inflammatory， promoting bone growth and protecting cardiovascular. But at the same time， many studies at home and abroad have found that taking Psoraleae Fructus and its compounds for a long time or in large doses can cause liver toxicity， phototoxicity， nephrotoxicity， etc. The most common is liver toxicity， most of the clinical reports on the toxicity of psoralen are caused by drug-induced liver injury events， which limits the clinical use of Psoraleae Fructus and can't exert its proper therapeutic effect. Therefore， it is particularly important to fully understand the toxicological mechanism of liver injury caused by Psoraleae Fructus and its attenuation methods. In this paper， by consulting the domestic and foreign related literatures in recent years that reported the hepatotoxicity of Psoraleae Fructus， the four aspects of clinical report on liver injury， hepatotoxic components， toxicological mechanisms and attenuation methods of Psoraleae Fructus were reviewed， including bile acid stasis and oxidative stress. The hepatotoxicity of Psoraleae Fructus was discussed in terms of reaction， mitochondrial damage， liver fat deformation， etc.， and the attenuation methods of Psoraleae Fructus were summarized from the aspects of compatibility attenuation and processing attenuation， aiming to comprehensively and objectively clarify Psoraleae Fructus. The potential toxicological mechanism of lipid-induced hepatotoxicity and research progress in attenuation were expected to provide a theoretical basis for further study of Psoraleae Fructus hepatotoxicity and clinical rational use of drugs.