ABSTRACT
The purpose of the present study was to examine the protective action and mechanisms of quercetin on the blood-brain barrier (BBB) in rats subjected to transient middle cerebral artery occlusion (tMCAO) and reperfusion. Quercetin (10, 30, 50 mg/kg) was intraperitoneally administered at the onset of reperfusion. The results showed that quercetin significantly reduced cerebral infarct volume, neurological deficit, BBB permeability and ROS generation via Sirt1/Nrf2/HO-1 signaling pathway. Moreover, EX527, a selective inhibitor of Sirt1, reversed these neuroprotective effects. Our findings indicate that quercetin has neuroprotective effects against cerebral ischemia-reperfusion injury by protecting BBB through Sirt1 signaling pathway in MCAO rats.
Subject(s)
Brain Ischemia , Neuroprotective Agents , Reperfusion Injury , Animals , Blood-Brain Barrier/metabolism , Brain Ischemia/drug therapy , Infarction, Middle Cerebral Artery/drug therapy , Molecular Structure , Neuroprotective Agents/pharmacology , Quercetin/pharmacology , Rats , Rats, Sprague-Dawley , Reperfusion Injury/drug therapy , Sirtuin 1ABSTRACT
In this study, bioinformatics methods such as molecular docking and network pharmacology were adopted to establish Xiaoxuming Decoction (XXMD) "compound-vasodilatory and vasoconstrictory related G protein-coupled receptors (GPCR) targets" network, then the vascular function regulatory effective components and the potential targets of XXMD were analyzed. Based on the XXMD herb sources, the chemical structures of the compounds were retrieved from the national scientific data sharing platform for population and health pharmaceutical information center, TCMSP database and the latest research literatures. The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties. Then, five kinds of vasodilatory and vasoconstrictory related GPCR crystal structure including 5-HT receptors (5-HT1AR, 5-HT1BR), AT1R, ß2-AR, hUTR and ETB were retrieved from RCSB Protein Data Bank database or constructed by homology modeling of Discovery Studio 4.1 built-in modeling tools. After virtual screening by Libdock molecular docking, the highest rated 50 compounds of each target were collected and analyzed. The collected data were further used to construct and analyze the network by Cytoscape 3.4.0. The results showed that most of the chemical composition effects were associated with different vasodilatory and vasoconstrictory related GPCR targets, while a few effective components could be applied to multiple GPCR targets at the same time, therefore forming synergies and vasorelaxant effects of XXMD.
