OBJECTIVE To investigate regulatory effects of hyperoside(Hyp)on IP3/PKC/TRPV4 pathway in rat cerebral basilar artery(CBA)subjected to global cerebral ischemia-reperfusion(I/R).METHODS The model of global cerebral I/R...OBJECTIVE To investigate regulatory effects of hyperoside(Hyp)on IP3/PKC/TRPV4 pathway in rat cerebral basilar artery(CBA)subjected to global cerebral ischemia-reperfusion(I/R).METHODS The model of global cerebral I/R in rats was established by four-vessel occlusions methods.The treated rats were administrated with Hyp(50 mg·kg^-1)group,Hyp(50 mg·kg^-1)+HC-067047(10 mg·kg^-1),Hyp(50 mg·kg^-1)+2APB(2 mg·kg^-1),Hyp(50 mg·kg^-1)+BisI(2.5 mg·kg^-1),Hyp(50 mg·kg^-1)+2APB(2 mg·kg^-1)+BisI(2.5 mg·kg^-1).Hematoxylin-eosin(HE)and Nissl staining were performed and the contents of methane dicarboxylic aldehyde(MDA),neuron-specific enolase(NSE),S100β and the activity of lactic dehydrogenase(LDH)in serum were measured by enzyme-linked immunosorbnent assay(ELISA).The specific blocker N-nitro-L-arginine-methyl-ester(L-NAME)and indomethacin(Indo)were used to delete the prostacyclin(PGI2)and nitric oxide(NO)dependent relaxation.The protein expression level of TRPV4 was detected by Western blotting.Ca2+intensity in vascular smooth muscle cells was measured by confocal laser scanning microscope and flow cytometry was performed to observe the apoptosis of CBA endothelial cells after in vivo administration.RESULTS Hyp induced a dose-dependent relaxation of CBA in IR rats via a PGI2 and NO independent manner,as evidenced by alleviated patho⁃logical changes and up-regulated expression of TRPV4 protein in the endothelial cells from cerebral vessels.Hyp signifi⁃cantly reduced the contents of MDA,NSE,S100βand the activity of LDH in serum and decreased the fluorescence intensity of Ca2+in cerebral vascular smooth muscle cells by in vivo administration.The apoptotic rate of endothelial cells in Hyp treated group was significantly less than that in IR group.CONCLUSION Hyp does in fact ameliorate I/R injury by regulatingIP3/PKC/TRPV4 pathway.展开更多
OBJECTIVE To predict the potential targets of hyperoside(Hyp)on improving ischemia/reperfusion injury by network pharmacology,and explore its possible mechanism combined with related literature.METHODS The action targ...OBJECTIVE To predict the potential targets of hyperoside(Hyp)on improving ischemia/reperfusion injury by network pharmacology,and explore its possible mechanism combined with related literature.METHODS The action targets of Hyp and ischemia/reperfusion injury were obtained by TCMSP,Swiss Target Prediction,Pharm Mapper,Similarity ensemble approach,Online Mendelian Inheritance in Man,DisGENT and database.The common targets of drugs and diseases were screened by Omishare and STRING database respectively,and the protein-protein interaction(PPI)network map was constructed.Then the interaction network between Hyp and disease targets was constructed by Cytoscape software and topological cross-linking analysis was carried out.Then the interaction network between Hyp and disease targets was constructed and cross-linked analysis was carried out by using Cytoscape software.The gene ontology(GO)of the core target was analyzed by David database,and then the related pathways of the core target were enriched by KEGG database.RESULTS A total of 54 GO enrichment processes were obtained by GO enrichment analysis of 44 common genes,including 38 biological processes(BP),15 cell composition(CC)processes,and 1 molecular functional(MF)process.43 items were obtained by signal pathway enrichment analysis in KEGG database.CONCLUSION It is suggested that the mechanism of Hyp may be related to PI3K-Akt,RAP1,RAS,VEGF and other signal transduction pathways.The above results laid a theoretical foundation for the study of the mechanism and clinical application of the treatment of ischemia/reperfusion injury.展开更多
OBJECTIVE Dengue virus belongs to the Flaviviridaefamily,and causes dengue fever and its related complications.Currently,there are no antiviral agents or licensed vaccines against dengue in humans.Houttuyniacordata Th...OBJECTIVE Dengue virus belongs to the Flaviviridaefamily,and causes dengue fever and its related complications.Currently,there are no antiviral agents or licensed vaccines against dengue in humans.Houttuyniacordata Thunb.(Saururaceae)is documented to possess antiviral activity against several medically important viruses.METHODS The in vitro activities of the total ethyl acetate(EA)extracts of two batches of H.cordata,five EA fractions,and four of its constituent polyphenols(chlorogenic acid,hyperoside,quercetin,and quercitrin)against the new guinea C strain of dengue-2 virus were investigated.RESULTS Using the plaque reduction test,the total EA extracts of H.cordatainhibited viral infectivity when pre-incubated with virus before the viral adsorption stage,but exhibited no dose-dependent response when added to the cells at 6h post-infection.The 50% inhibitory concentration(IC50)of total EA extracts from two batches of H.cordata added before the viral adsorption stage were 0.24±3.1μg·mL-1 and 0.04±4.6μg·mL-1.However,only one out of five tested EA fractions showed considerably- weaker IC50 of 333μg·mL1.The pure polyphenol compounds displayed some anti-dengue activity,with their combinations yielding greater antiviral effects,especially the combination of chlorogenic acid and hyperoside with a high selectivity index.However,the enhanced efficacy of the polyphenol combinations was still less than that of the total EA extracts which revealed absence of cytotoxicity.Therefore,there may be other compounds in H.cordatathat contribute to the superior efficacy of the EA extracts.CONCLUSION We conclude that H.cordata possesses anti-dengue-2 virus activity,and harbors potential for the development of antiviral agents against dengue.展开更多
基金National Natural Science Foundation of China(81173596)Natural Science Foundation of the Department of Education of Anhui Province(KJ2015A157)
文摘OBJECTIVE To investigate regulatory effects of hyperoside(Hyp)on IP3/PKC/TRPV4 pathway in rat cerebral basilar artery(CBA)subjected to global cerebral ischemia-reperfusion(I/R).METHODS The model of global cerebral I/R in rats was established by four-vessel occlusions methods.The treated rats were administrated with Hyp(50 mg·kg^-1)group,Hyp(50 mg·kg^-1)+HC-067047(10 mg·kg^-1),Hyp(50 mg·kg^-1)+2APB(2 mg·kg^-1),Hyp(50 mg·kg^-1)+BisI(2.5 mg·kg^-1),Hyp(50 mg·kg^-1)+2APB(2 mg·kg^-1)+BisI(2.5 mg·kg^-1).Hematoxylin-eosin(HE)and Nissl staining were performed and the contents of methane dicarboxylic aldehyde(MDA),neuron-specific enolase(NSE),S100β and the activity of lactic dehydrogenase(LDH)in serum were measured by enzyme-linked immunosorbnent assay(ELISA).The specific blocker N-nitro-L-arginine-methyl-ester(L-NAME)and indomethacin(Indo)were used to delete the prostacyclin(PGI2)and nitric oxide(NO)dependent relaxation.The protein expression level of TRPV4 was detected by Western blotting.Ca2+intensity in vascular smooth muscle cells was measured by confocal laser scanning microscope and flow cytometry was performed to observe the apoptosis of CBA endothelial cells after in vivo administration.RESULTS Hyp induced a dose-dependent relaxation of CBA in IR rats via a PGI2 and NO independent manner,as evidenced by alleviated patho⁃logical changes and up-regulated expression of TRPV4 protein in the endothelial cells from cerebral vessels.Hyp signifi⁃cantly reduced the contents of MDA,NSE,S100βand the activity of LDH in serum and decreased the fluorescence intensity of Ca2+in cerebral vascular smooth muscle cells by in vivo administration.The apoptotic rate of endothelial cells in Hyp treated group was significantly less than that in IR group.CONCLUSION Hyp does in fact ameliorate I/R injury by regulatingIP3/PKC/TRPV4 pathway.
基金National Natural Science Foundation of China(81170148)and Major Project of Natural Science Foundation of the Department of Education of Anhui Province(KJ2019ZD32)。
文摘OBJECTIVE To predict the potential targets of hyperoside(Hyp)on improving ischemia/reperfusion injury by network pharmacology,and explore its possible mechanism combined with related literature.METHODS The action targets of Hyp and ischemia/reperfusion injury were obtained by TCMSP,Swiss Target Prediction,Pharm Mapper,Similarity ensemble approach,Online Mendelian Inheritance in Man,DisGENT and database.The common targets of drugs and diseases were screened by Omishare and STRING database respectively,and the protein-protein interaction(PPI)network map was constructed.Then the interaction network between Hyp and disease targets was constructed by Cytoscape software and topological cross-linking analysis was carried out.Then the interaction network between Hyp and disease targets was constructed and cross-linked analysis was carried out by using Cytoscape software.The gene ontology(GO)of the core target was analyzed by David database,and then the related pathways of the core target were enriched by KEGG database.RESULTS A total of 54 GO enrichment processes were obtained by GO enrichment analysis of 44 common genes,including 38 biological processes(BP),15 cell composition(CC)processes,and 1 molecular functional(MF)process.43 items were obtained by signal pathway enrichment analysis in KEGG database.CONCLUSION It is suggested that the mechanism of Hyp may be related to PI3K-Akt,RAP1,RAS,VEGF and other signal transduction pathways.The above results laid a theoretical foundation for the study of the mechanism and clinical application of the treatment of ischemia/reperfusion injury.
基金The project supported by a research grant from the National University of Singapore
文摘OBJECTIVE Dengue virus belongs to the Flaviviridaefamily,and causes dengue fever and its related complications.Currently,there are no antiviral agents or licensed vaccines against dengue in humans.Houttuyniacordata Thunb.(Saururaceae)is documented to possess antiviral activity against several medically important viruses.METHODS The in vitro activities of the total ethyl acetate(EA)extracts of two batches of H.cordata,five EA fractions,and four of its constituent polyphenols(chlorogenic acid,hyperoside,quercetin,and quercitrin)against the new guinea C strain of dengue-2 virus were investigated.RESULTS Using the plaque reduction test,the total EA extracts of H.cordatainhibited viral infectivity when pre-incubated with virus before the viral adsorption stage,but exhibited no dose-dependent response when added to the cells at 6h post-infection.The 50% inhibitory concentration(IC50)of total EA extracts from two batches of H.cordata added before the viral adsorption stage were 0.24±3.1μg·mL-1 and 0.04±4.6μg·mL-1.However,only one out of five tested EA fractions showed considerably- weaker IC50 of 333μg·mL1.The pure polyphenol compounds displayed some anti-dengue activity,with their combinations yielding greater antiviral effects,especially the combination of chlorogenic acid and hyperoside with a high selectivity index.However,the enhanced efficacy of the polyphenol combinations was still less than that of the total EA extracts which revealed absence of cytotoxicity.Therefore,there may be other compounds in H.cordatathat contribute to the superior efficacy of the EA extracts.CONCLUSION We conclude that H.cordata possesses anti-dengue-2 virus activity,and harbors potential for the development of antiviral agents against dengue.
