Identify potential treatments of COVID-19 from Tibetan medicine Hippophae Fructus using a network pharmacological approach

OBJECTIVE Since the coronavirus disease 2019(COVID-19)outbreak in December 2019,the search for a potential treatment for COVID-19 has been a constant focus.Therefore,we identified potential treatments for COVID-19 from Hippophae Fructus,a Tibetan medicine that may act on COVID-19,using a network pharmacology approach.METHODS We collected the chemical constituents and corresponding targets of Hippophae Fructus from traditional Chinese medicine system pharmacology(TCMSP).COVID-19 related genes were predicted in pubmed-Gene,OMIM and GeneCards databases.Then,protein-protein interactions(PPIs)of key genes were analyzed by STRING database.Compound-target-diseases network was constructed using Cytoscape software.The potential pathways were determined by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses.Additionally,molecular docking was used to verify the binding effect between the active component and the target.RESULTS A total of 33 components and 192 corresponding targets in Hippophae Fructus were found.50 genes were obtained from the intersection of component targets and disease targets.These genes include IL-6,TNF,MAPK8 and PTGS2,which regulate several pathways associated with COVID-19,involving Hepatitis B,Influenza A,TNF signaling pathway and Tuberculosis.More importantly,high-node compounds such as quercetin and beta-sitosterol can well bind to key targets.CONCLUSION Some components in Hippophae Fructus can act on COVID-19 related genes and regulate multiple pathways.Perhaps Hippophae Fructus has the effect in treating COVID-19.

nfluence and mechanism of Xindakang on cardiac functions of isolated frog heart

OBJECTIVE To evaluate the effects of flavonoids from Xindakang(Hippophae Fructus flavone)on myocardial systolic and diastolic functions of isolated frog hearts and explore the possible mechanism,and provide experimental basis for improving the effect and efficacy of Xindakang on cardiac function.METHODS The isolated frog heart perfusion specimens were prepared by Yagi′s method,and the effects of different concentrations of Xindakang on myocardial contractility(0.0125,0.025,0.05,0.1 and 0.2 g·L^(-1)),heart rate and cardiac output of isolated frog heart were studied.Acetylcholine,atropine and epinephrine were administered successively to analyze the effects of Xindakang on cardiac systolic function of isolated frogs under the action of different drugs,and compared with propranolol.The effect of extracellular calcium ion concentration on the action of Xindakang was studied by using low calcium concentration,high calcium concentration and normal Ren′s solution.To study the effect and possible mechanism of Xindakang on cardiac systolic function of frog.RESULTS The concentration of Xindakang in the range of 0.0125-0.1 g·L^(-1)could weaken the contractility of isolated frog heart and increase the concentration of Xindakang.The inhibitory effect of Xindakang on contractility of isolated frog heart was enhanced,and showed obvious dose-effect relationship.Cardiac output was significantly decreased by Xindakang(P<0.01),slow heart rate(P<0.05);M receptor blocker atropine could not antagonize the contractile effect of Xindakang,and Xindakang could not completely antagonize the contractile effect of adrenalin.Xindakang could inhibit the isolated frog heart in low calcium concentration,high calcium concentration and normal Ren′s solution,and increased with the increase of extracellular calcium concentration(P<0.01).CONCLUSION Xindakang has inhibitory effect on isolated frog heart,which may be achieved by blocking the calcium channel on myocardial cell membrane and reducing the calcium concentration in myocardial cells.