OBJECTIVE Using bioinformatics methods,to establish Xiao-Xu-Ming decoction(XX.MD) "compound-vasoconstriction G Protein-Coupled Receptors(GPCR) targets" network,and analyze the vasoconstriction regulatory eff...OBJECTIVE Using bioinformatics methods,to establish Xiao-Xu-Ming decoction(XX.MD) "compound-vasoconstriction G Protein-Coupled Receptors(GPCR) targets" network,and analyze the vasoconstriction regulatory effective components and the potential targets of XXMD.METHODS Ac.cording to the XXMD herb sources,we retrieved the chemical structures from the national scientific da.ta sharing platform for population and health pharmaceutical information center,TCMSP database and the latest research literature.The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties.Five kinds of vasoconstriction GPCR crystal structure including 5-HT receptors(5-HT1 AR,5-HT1 BR),AT1 R,β2-AR,hUTR and ETB were retrieved from Bank Pro.tein Data Bank database or homology modeling using Discovery Studio 4.1 built-in modeling tools.After virtual screening by Libdock molecular docking,the highest rated 50 compounds of each target were col.lected and analyzed.The collected data were further used to construct and analyze the network.RE.SULTS 859 single compound structures information in XXMD were generalized following the screen.ing of obtained 2043 compounds.The complicated compound-vasoconstriction GPCR targets network of XXMD was then constructed and analyzed by molecular docking with the above five kinds of GPCR target receptors.Most of the chemical composition effects were associated with different vasoconstric.tion GPCR targets,while a few effective components can be applied to multiple GPCR targets at the same time,therefore forming synergies.CONCLUSION Vasorelaxant effects of XXMD may not only result from the collaborative interaction between a variety of active ingredients in Chinese medicine and multi.ple targets,but also from the interaction between some effective component and multiple targets.展开更多
Carpesii Fructus is the fruit of Carpesium abrotanoides L.and is recorded in the Chinese Pharmacopoeia(2015 Edition).Carpesium abrotanoides broadly distribute in China.Traditionally,Carpesii Fructus was used as a para...Carpesii Fructus is the fruit of Carpesium abrotanoides L.and is recorded in the Chinese Pharmacopoeia(2015 Edition).Carpesium abrotanoides broadly distribute in China.Traditionally,Carpesii Fructus was used as a parasiticide,especially for ascariasis,pinworms and tapeworm disease.In ancient times,the Carpesium plants were used as traditional Chinese,Korean and Japanese herbal medicines for the treatment of several diseases.Carpesii Fructus was first recorded in the book "Newly Revised Canon of Materia Medica" in the Tang Dynasty of China.The original plant is Compositae Arte.misia santonica(Seriphidium cinum) from middle east Persian.At present,Carpesium abrotanoides issometimes confused with the Lappula family in species classification.In the Song Dynasty of China,"KaiYang Materia Medica" recorded that the best Carpesii Fructus was from Persian.The main compo.nents of Carpesii Fructusare terpenes,phenolic compounds,flavonoids and coumarins.Including telekin,3-epi-isotelekin,11β-13-dihydro-1-epi-inuviscolide,carabrone,carabrol,terpene lactone,gerilin,carpesia,valeric acid,oleic acid,linolenic acid,thirty-one alkane,sterol,etc.The chemical components isolated from whole plants of carpesia are more than 143.In clinical practice,Carpesii Fructus is mainly used as antiparasitic drugs and usually combined with other drugs since the poor efficacy as single drug.Its toxic reaction is closely related to the dose of the drug.Carpesia,asa main component of Carpesii Fructus,might lead to adverse reactions also.At present,Major issuesof Carpesii Fructusare the lack of phar.macological research,as well as lack of in-depth study on the material basis.Therefore,further studies are needed on the drug development and clinical usuage.展开更多
OBJECTIVE To enhance the quality and efficiency of chlorogeninc acid by investigating the differences among the chlorogeninc acid polymorphs in bioavailability and solubility.METHODS Determinative method was used to a...OBJECTIVE To enhance the quality and efficiency of chlorogeninc acid by investigating the differences among the chlorogeninc acid polymorphs in bioavailability and solubility.METHODS Determinative method was used to analyze the solubility of chlorogeninc acid polymorphs;solid chlorogeninc acid in different forms were orally administered to the rats,and a HPLC method was established to determinate plasma lever of metabolite-acyclovir and the bioavailability was analyzed.RESULTS The indirect pharmacokinetic parameters of Chlorogeninc acid,as the metabolites of the form Ⅰ,Ⅱ,Ⅲ,were as follows:cmaxwas 0.37,0.34 and 0.44mg·L-1,respectively;AUC0→twas 0.71,0.76 and 0.79mg·L-1·h,respectively.CONCLUSION The solubility of form Ⅲ was larger than the other forms′.The solubility of Chlorogeninc acid polymorphs:form Ⅰ,form Ⅱ,form Ⅲ were merely the same,there was no statistically significant difference in pharmacokinetic parameters among these three forms.展开更多
OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was ...OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was applied to the rightcerebral ventricle immediately after transient middle cerebral artery occlusion.Brain water content,Evans blue leakage and the expression of aquaporin-4(AQP-4),matrix metalloproteinase-9(MMP-9),zonula occludens-1(ZO-1)and occludin were measured.RESULTS After treatment with antiCKLF1 antibody,brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion,but not changed in contralateral hemisphere.Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9,and upregulated the expression of ZO-1 and Occludin.These results suggest that CKLF1 is involved in BBB disruption after reperfusion.CONCLUSION Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity,possibly via inhibiting the expression of AQP-4 and MMP-9,and increasing the expression of tight junction protein.展开更多
OBJECTIVE To investigate the cerebralvasorelaxant material basis of Xiaoxuming decoction.METHODS According to the Xiaoxuming decoction herb sources,we retrieved the chemical structure from the literatures and the Chin...OBJECTIVE To investigate the cerebralvasorelaxant material basis of Xiaoxuming decoction.METHODS According to the Xiaoxuming decoction herb sources,we retrieved the chemical structure from the literatures and the Chinese Natural Product Database(http://pharmdata.ncmi.cn).By using microvessel tension system,we checked the vasorelaxanteffects of Xiaoxuming decoction anti-cerebral ischemia effective components group(XXMDECG)and the available composition compounds on pre-contracted basilar artery ring.RESULTS963 compoundsin the decoction,including 81Fangfeng,77 Mahuang,130 Shengjiang,31 Guizhi,91 Huangqin,127 Renshen,73 Chuanxiong,44 Shaoyao,39 Xingren,42 Fangji,62 Fuzi and 166 Gancao were collected.The five largest number classes of compounds in the decoction are volatile oil(32%),flavone(32%),alkaloid(13%),saponin(7%),polyphenol and organic acid(5%).XXMDECG at concentration from 1 to 400μg·mL-1can dilate the KCl(60 mmol·L-1)and ET-1(0.01μmol·L-1)pre-contracted rat basilar artery rings in a dose-dependent manner.There are 6 compounds with vasorelaxant ratio more than 50%at the concentration of 10μmol·L-1.CONCLUSION Xiaoxuming decoction contains abundant chemical structure.It has the material basis of multiple ingredients and multiple targets.The XXMDECG are able to dilate the rat basilar artery rings in a dose-dependent manner.The network interactions between varies of chemical compounds in Xiaoxuming decoction and the vasoconstriction associated targets result in the comprehensive regulation mechanisms of vascular function.展开更多
基金supported by Major Scientific and Technological Project of China(2013ZX095081042013ZX09402203)+1 种基金 CAMS Innovation Fund for Medical Sciences(2016-I2M-3-007) Central Public Scientific Re.search Institution Fundamental Project(2014CX05)
文摘OBJECTIVE Using bioinformatics methods,to establish Xiao-Xu-Ming decoction(XX.MD) "compound-vasoconstriction G Protein-Coupled Receptors(GPCR) targets" network,and analyze the vasoconstriction regulatory effective components and the potential targets of XXMD.METHODS Ac.cording to the XXMD herb sources,we retrieved the chemical structures from the national scientific da.ta sharing platform for population and health pharmaceutical information center,TCMSP database and the latest research literature.The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties.Five kinds of vasoconstriction GPCR crystal structure including 5-HT receptors(5-HT1 AR,5-HT1 BR),AT1 R,β2-AR,hUTR and ETB were retrieved from Bank Pro.tein Data Bank database or homology modeling using Discovery Studio 4.1 built-in modeling tools.After virtual screening by Libdock molecular docking,the highest rated 50 compounds of each target were col.lected and analyzed.The collected data were further used to construct and analyze the network.RE.SULTS 859 single compound structures information in XXMD were generalized following the screen.ing of obtained 2043 compounds.The complicated compound-vasoconstriction GPCR targets network of XXMD was then constructed and analyzed by molecular docking with the above five kinds of GPCR target receptors.Most of the chemical composition effects were associated with different vasoconstric.tion GPCR targets,while a few effective components can be applied to multiple GPCR targets at the same time,therefore forming synergies.CONCLUSION Vasorelaxant effects of XXMD may not only result from the collaborative interaction between a variety of active ingredients in Chinese medicine and multi.ple targets,but also from the interaction between some effective component and multiple targets.
基金supported by CAMS Initiative for Innovative Medicine(CAMS-I2M,2016II2M-3-007) National Natural Science Foundation of China(81470159)
文摘Carpesii Fructus is the fruit of Carpesium abrotanoides L.and is recorded in the Chinese Pharmacopoeia(2015 Edition).Carpesium abrotanoides broadly distribute in China.Traditionally,Carpesii Fructus was used as a parasiticide,especially for ascariasis,pinworms and tapeworm disease.In ancient times,the Carpesium plants were used as traditional Chinese,Korean and Japanese herbal medicines for the treatment of several diseases.Carpesii Fructus was first recorded in the book "Newly Revised Canon of Materia Medica" in the Tang Dynasty of China.The original plant is Compositae Arte.misia santonica(Seriphidium cinum) from middle east Persian.At present,Carpesium abrotanoides issometimes confused with the Lappula family in species classification.In the Song Dynasty of China,"KaiYang Materia Medica" recorded that the best Carpesii Fructus was from Persian.The main compo.nents of Carpesii Fructusare terpenes,phenolic compounds,flavonoids and coumarins.Including telekin,3-epi-isotelekin,11β-13-dihydro-1-epi-inuviscolide,carabrone,carabrol,terpene lactone,gerilin,carpesia,valeric acid,oleic acid,linolenic acid,thirty-one alkane,sterol,etc.The chemical components isolated from whole plants of carpesia are more than 143.In clinical practice,Carpesii Fructus is mainly used as antiparasitic drugs and usually combined with other drugs since the poor efficacy as single drug.Its toxic reaction is closely related to the dose of the drug.Carpesia,asa main component of Carpesii Fructus,might lead to adverse reactions also.At present,Major issuesof Carpesii Fructusare the lack of phar.macological research,as well as lack of in-depth study on the material basis.Therefore,further studies are needed on the drug development and clinical usuage.
基金The project supported by the Ministry of Science and Technology of China(2007FY130100)the 12th Five-Year Plan project(2012ZX09301002-001-013)
文摘OBJECTIVE To enhance the quality and efficiency of chlorogeninc acid by investigating the differences among the chlorogeninc acid polymorphs in bioavailability and solubility.METHODS Determinative method was used to analyze the solubility of chlorogeninc acid polymorphs;solid chlorogeninc acid in different forms were orally administered to the rats,and a HPLC method was established to determinate plasma lever of metabolite-acyclovir and the bioavailability was analyzed.RESULTS The indirect pharmacokinetic parameters of Chlorogeninc acid,as the metabolites of the form Ⅰ,Ⅱ,Ⅲ,were as follows:cmaxwas 0.37,0.34 and 0.44mg·L-1,respectively;AUC0→twas 0.71,0.76 and 0.79mg·L-1·h,respectively.CONCLUSION The solubility of form Ⅲ was larger than the other forms′.The solubility of Chlorogeninc acid polymorphs:form Ⅰ,form Ⅱ,form Ⅲ were merely the same,there was no statistically significant difference in pharmacokinetic parameters among these three forms.
基金The project supported by National Natural Science Foundation of China(81302760)the Chinese Postdoctoral Science Foundation Project(2013M542510)
文摘OBJECTIVE To investigate the role of chemokine-like factor 1(CKLF1),a novel C-C chemokine,on brain-blood barrier(BBB)integrity in rat focal cerebral ischemia and reperfusion model.METHODS Antibodies against CKLF1 was applied to the rightcerebral ventricle immediately after transient middle cerebral artery occlusion.Brain water content,Evans blue leakage and the expression of aquaporin-4(AQP-4),matrix metalloproteinase-9(MMP-9),zonula occludens-1(ZO-1)and occludin were measured.RESULTS After treatment with antiCKLF1 antibody,brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24 h after reperfusion,but not changed in contralateral hemisphere.Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9,and upregulated the expression of ZO-1 and Occludin.These results suggest that CKLF1 is involved in BBB disruption after reperfusion.CONCLUSION Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity,possibly via inhibiting the expression of AQP-4 and MMP-9,and increasing the expression of tight junction protein.
基金The project supported by Major Scientific and Technological Special Project for "Significant New Drug Creation"(2013ZX09508104,2013ZX09402203)by Central Public Scientific Research Institution Fundamental Project(2014CX05)
文摘OBJECTIVE To investigate the cerebralvasorelaxant material basis of Xiaoxuming decoction.METHODS According to the Xiaoxuming decoction herb sources,we retrieved the chemical structure from the literatures and the Chinese Natural Product Database(http://pharmdata.ncmi.cn).By using microvessel tension system,we checked the vasorelaxanteffects of Xiaoxuming decoction anti-cerebral ischemia effective components group(XXMDECG)and the available composition compounds on pre-contracted basilar artery ring.RESULTS963 compoundsin the decoction,including 81Fangfeng,77 Mahuang,130 Shengjiang,31 Guizhi,91 Huangqin,127 Renshen,73 Chuanxiong,44 Shaoyao,39 Xingren,42 Fangji,62 Fuzi and 166 Gancao were collected.The five largest number classes of compounds in the decoction are volatile oil(32%),flavone(32%),alkaloid(13%),saponin(7%),polyphenol and organic acid(5%).XXMDECG at concentration from 1 to 400μg·mL-1can dilate the KCl(60 mmol·L-1)and ET-1(0.01μmol·L-1)pre-contracted rat basilar artery rings in a dose-dependent manner.There are 6 compounds with vasorelaxant ratio more than 50%at the concentration of 10μmol·L-1.CONCLUSION Xiaoxuming decoction contains abundant chemical structure.It has the material basis of multiple ingredients and multiple targets.The XXMDECG are able to dilate the rat basilar artery rings in a dose-dependent manner.The network interactions between varies of chemical compounds in Xiaoxuming decoction and the vasoconstriction associated targets result in the comprehensive regulation mechanisms of vascular function.
