Xiao-Xu-Ming decoction has been widely used to treat stroke and sequelae of stroke. We have previously shown that the active fractions of Xiao-Xu-Ming decoction attenuate cerebral ischemic injury. However, the global ...Xiao-Xu-Ming decoction has been widely used to treat stroke and sequelae of stroke. We have previously shown that the active fractions of Xiao-Xu-Ming decoction attenuate cerebral ischemic injury. However, the global protein profile and signaling conduction pathways regulated by Xiao-Xu-Ming decoction are still unclear. This study established a two-vessel occlusion rat model by bilateral common carotid artery occlusion. Rats were intragastrically administered 50 or 150 mg/kg Xiao-Xu-Ming decoction for 4 consecutive weeks. Learning and memory abilities were measured with Morris water maze. Motor ability was detected with prehensile test. Coordination ability was examined using the inclined screen test. Neuronal plasticity was observed by immunofluorescent staining. Differentially expressed proteins of rat hippocampus were analyzed by label-free quantitative proteomics. Real time-polymerase chain reaction and western blot assay were used to identify the changes in proteins. Results showed that Xiao-Xu-Ming decoction dramatically alleviated learning and memory deficits, and motor and coordination dysfunction, and increased the expression of microtubule-associated protein 2. Xiao-Xu-Ming decoction extract remarkably decreased 13 upregulated proteins and increased 39 downregulated proteins. The regulated proteins were mainly involved in oxidation reduction process, intracellular signaling cascade process, and protein catabolic process. The signaling pathways were mainly involved in ubiquitin mediated proteolysis and the phosphatidylinositol signaling system. Furthermore, there was an interaction among Rab2 a, Ptpn1, Ppm1 e, Cdk18, Gorasp2, Eps15, Capza2, Syngap1 and Mt-nd1. Protein analyses confirmed the changes in expression of MTND1. The current findings provide new insights into the molecular mechanisms of Xiao-Xu-Ming decoction extract's effects on chronic cerebral hypoperfusion.展开更多
OBJECTIVE Xiao-xu-ming decoction(XXMD),a well-known traditional Chinese herbal prescription,has been widely used to treat stroke.It is recorded in″Bei Ji Qian Jin Yao Fang″written by Si-miao Sun of the Chinese ancie...OBJECTIVE Xiao-xu-ming decoction(XXMD),a well-known traditional Chinese herbal prescription,has been widely used to treat stroke.It is recorded in″Bei Ji Qian Jin Yao Fang″written by Si-miao Sun of the Chinese ancient Tang Dynasty.In our previous study,the active fraction of XXMD(XXM)against cerebral ischemia has been prepared by modern separation and purification techniques.This study was to investigate XXM against lipopolysaccaride(LPS)-induced neuroinflammation in mice.METHODS LPS is an endotoxin from the outer membrane of Gram-negative bacteria that activates inflammation.XXM was pre-treated in BALB/C mice followed by injected intraperitoneally with LPS(5 mg·kg-1).The effects of XXM on LPS-induced pro-inflammatory factors and proteins were measured by ELISA,Western blot,and immunofluorescence in vivo.RESULTS Mice treated with XXM showed significantly decreased proinflammatory factors level,including IL-1β(P<0.01),IL-6(P<0.01),TNF-α(P<0.05),and MCP-1(P<0.01).Furthermore,XXM also significantly inhibited the inflammatory pathway proteins expression induced by LPS,including TLR4,MyD 88,and COX-2.CONCLUSION XXM possesses anti-neuroinflammation in mice and might be a promising therapeutic agent for stroke.展开更多
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
OBJECTIVE Vascular dementia(VD) refers to a progressive decline in memory and cognitive function caused by chronic cerebral ischemia.2-Vessels occlusion(2-VO) has been widely used as a model of VD.Xiao-Xu-Ming decocti...OBJECTIVE Vascular dementia(VD) refers to a progressive decline in memory and cognitive function caused by chronic cerebral ischemia.2-Vessels occlusion(2-VO) has been widely used as a model of VD.Xiao-Xu-Ming decoction,a well-known traditional Chinese medicine prescrip.tion,has been widely used to treat stroke and sequelae of stroke.The present study was to investigate the mechanism of Xiao-Xu-Ming decoction(XXM) against chronic cerebral ischemia injury in rats.METHODS After XXM treatment,rats were performed a memory testing with Morris water maze and motor ability testing using prehensile test and inclined screen test.Neuronal plasticity was observed by immunofluorescent staining with MAP2 antibody.Differentially expressed proteins of rat hippocampus were analyzed by Label-free quantitative proteomics.RESULTS XXM significantly alleviated 2-VOinduced learning and memory deficits,motor ability dysfunction,and neuronal plasticity injury in rats.The mechanism might be involved in up-regulation of 39 proteins and down-regulation of 13 proteins in the hippocampus of rats after XXM treatment vs 2-VO group rats.Gene ontology and pathway analysis showed that the regulated proteins are mainly involved in oxidation reduction process,intracellular signaling cascade process,and protein catabolic process,etc.The signal pathways are mainly involved in ubiquitin mediated proteolysis and phosphatidylinositol signaling system.CONCLUSION Current findings provide new insights into the molecular mechanisms of XXM on chronic cerebral ischemia.展开更多
基金supported in part by the National Natural Science Foundation of China,No.81473383(to YHW)the Significant New-Drugs Creation of Science and Technology Major Projects in China,No.2018ZX09711001-003-019(to YHW)the Innovation Fund for Graduate of Beijing Union Medical College of China,No.2017-1007-02(to XC)
文摘Xiao-Xu-Ming decoction has been widely used to treat stroke and sequelae of stroke. We have previously shown that the active fractions of Xiao-Xu-Ming decoction attenuate cerebral ischemic injury. However, the global protein profile and signaling conduction pathways regulated by Xiao-Xu-Ming decoction are still unclear. This study established a two-vessel occlusion rat model by bilateral common carotid artery occlusion. Rats were intragastrically administered 50 or 150 mg/kg Xiao-Xu-Ming decoction for 4 consecutive weeks. Learning and memory abilities were measured with Morris water maze. Motor ability was detected with prehensile test. Coordination ability was examined using the inclined screen test. Neuronal plasticity was observed by immunofluorescent staining. Differentially expressed proteins of rat hippocampus were analyzed by label-free quantitative proteomics. Real time-polymerase chain reaction and western blot assay were used to identify the changes in proteins. Results showed that Xiao-Xu-Ming decoction dramatically alleviated learning and memory deficits, and motor and coordination dysfunction, and increased the expression of microtubule-associated protein 2. Xiao-Xu-Ming decoction extract remarkably decreased 13 upregulated proteins and increased 39 downregulated proteins. The regulated proteins were mainly involved in oxidation reduction process, intracellular signaling cascade process, and protein catabolic process. The signaling pathways were mainly involved in ubiquitin mediated proteolysis and the phosphatidylinositol signaling system. Furthermore, there was an interaction among Rab2 a, Ptpn1, Ppm1 e, Cdk18, Gorasp2, Eps15, Capza2, Syngap1 and Mt-nd1. Protein analyses confirmed the changes in expression of MTND1. The current findings provide new insights into the molecular mechanisms of Xiao-Xu-Ming decoction extract's effects on chronic cerebral hypoperfusion.
基金The project supported by National Natural Science Foundation of China(81473383,81573645)
文摘OBJECTIVE Xiao-xu-ming decoction(XXMD),a well-known traditional Chinese herbal prescription,has been widely used to treat stroke.It is recorded in″Bei Ji Qian Jin Yao Fang″written by Si-miao Sun of the Chinese ancient Tang Dynasty.In our previous study,the active fraction of XXMD(XXM)against cerebral ischemia has been prepared by modern separation and purification techniques.This study was to investigate XXM against lipopolysaccaride(LPS)-induced neuroinflammation in mice.METHODS LPS is an endotoxin from the outer membrane of Gram-negative bacteria that activates inflammation.XXM was pre-treated in BALB/C mice followed by injected intraperitoneally with LPS(5 mg·kg-1).The effects of XXM on LPS-induced pro-inflammatory factors and proteins were measured by ELISA,Western blot,and immunofluorescence in vivo.RESULTS Mice treated with XXM showed significantly decreased proinflammatory factors level,including IL-1β(P<0.01),IL-6(P<0.01),TNF-α(P<0.05),and MCP-1(P<0.01).Furthermore,XXM also significantly inhibited the inflammatory pathway proteins expression induced by LPS,including TLR4,MyD 88,and COX-2.CONCLUSION XXM possesses anti-neuroinflammation in mice and might be a promising therapeutic agent for stroke.
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 National Natural Science Foundation of China(81473383) National Science and Technology Major Project of China(2018ZX09711001-003-019)+1 种基金 CAMS Innovation Fund for Medical Sciences(2016-I2M-3-007) Innovation Fund for Graduate of Beijing Union M
文摘OBJECTIVE Vascular dementia(VD) refers to a progressive decline in memory and cognitive function caused by chronic cerebral ischemia.2-Vessels occlusion(2-VO) has been widely used as a model of VD.Xiao-Xu-Ming decoction,a well-known traditional Chinese medicine prescrip.tion,has been widely used to treat stroke and sequelae of stroke.The present study was to investigate the mechanism of Xiao-Xu-Ming decoction(XXM) against chronic cerebral ischemia injury in rats.METHODS After XXM treatment,rats were performed a memory testing with Morris water maze and motor ability testing using prehensile test and inclined screen test.Neuronal plasticity was observed by immunofluorescent staining with MAP2 antibody.Differentially expressed proteins of rat hippocampus were analyzed by Label-free quantitative proteomics.RESULTS XXM significantly alleviated 2-VOinduced learning and memory deficits,motor ability dysfunction,and neuronal plasticity injury in rats.The mechanism might be involved in up-regulation of 39 proteins and down-regulation of 13 proteins in the hippocampus of rats after XXM treatment vs 2-VO group rats.Gene ontology and pathway analysis showed that the regulated proteins are mainly involved in oxidation reduction process,intracellular signaling cascade process,and protein catabolic process,etc.The signal pathways are mainly involved in ubiquitin mediated proteolysis and phosphatidylinositol signaling system.CONCLUSION Current findings provide new insights into the molecular mechanisms of XXM on chronic cerebral ischemia.
