ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Objective:To investigate the effect of alcohol extract of Magnoliae Officinalis Cortex,alcohol extract of Polygalae Radix and their compatibility on fecal metabolites of rats,analyze its potential metabolic pathways,and provide experimental basis for exploring the possible mechanism of Magnoliae Officinalis Cortex relieving gastrointestinal motility disorders induced by Polygalae Radix. Method:Forty male SD rats were randomly divided into the normal group,alcohol extract of Magnoliae Officinalis Cortex group(3.50 g·kg-1),alcohol extract of Polygalae Radix group(1.75 g·kg-1) and compatibility group (3.5 g·kg-1 of alcohol extract of Magnoliae Officinalis Cortex+1.75 g·kg-1 of alcohol extract of Polygalae Radix).Fecal samples were collected within 24 h after continuous gavage for 3 days.The fecal metabolites in each group was detected by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS),mobile phase was acetonitrile-0.1%formic acid solution for gradient elution,data collection range was m/z 50-1 200 under positive and negative ion mode of electrospray ionization.The characteristic biomarkers and corresponding metabolic pathways were analyzed or screened by Progenesis QI v2.0,SIMCA-P 14.0,SPSS 20.0,MetaboAnalyst 4.0 and other softwares. Result:A total of 17 characteristic metabolic markers were screened out,including 5-formiminotetrahydrofolic acid,L-3-hydroxykynurenine,7,8-dihydropteroic acid,etc.The main related pathways included biosynthesis of unsaturated fatty acids,linoleic acid metabolism,vitamin B6 metabolism,etc. Conclusion:The mechanism of Magnoliae Officinalis Cortex relieving gastrointestinal motility disorders induced by Polygalae Radix may be related to purine metabolism,folate biosynthesis,tryptophan metabolism and primary bile acid biosynthesis.