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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-VO-induced 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.
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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-HT1AR,5-HT1BR),AT1R,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.
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OBJECTIVE: To investigate the protective effects of the effective components group of Xiao-Xu-Ming decoction (XXM) on focal cerebral ischemia rats. METHODS: The model of focal cerebral ischemia was made by middle cerebral artery occlusion (MCAO) with nylon suture. The neuroethological score and the staying time on slope board were gotten after 48 h of the operation. The percentage of cerebral infarction volume to total brain volume was calculated by TTC staining. Furthermore, the content of MDA, the activities of SOD and GSH-Px, and the activity of NOS in the brain tissue were detected by photospectrometer analysis system. RESULTS: The effective components group of Xiao-Xu-Ming decoction could significantly reduce the scores of neurological deficits , alleviate the cerebral infarction volume, improve the activity of SOD, reduce the content of MDA, and decrease the activity of iN-OS, but have no effect on the activity of GSH-Px. CONCLUSION: The effective components group of Xiao-Xu-Ming decoction may attenuate the focal cerebral ischemia injury in rats, and the mechanism is related to regulate the balance between oxidation and anti-oxidation and decrease the activity of iNOS in the brain tissue. Copyright 2012 by the Chinese Pharmaceutical Association.