ABSTRACT
Danshen injection (DI) is effective in treating cardiovascular and cerebrovascular diseases, including ischemic stroke (IS), including IS, but its mechanism is unclear. A middle cerebral artery occlusion model was used to simulate ischemia/reperfusion (I/R) injury in SD rats. Overexpression of hypoxia-inducible factor 1α (HIF-1α) was achieved by AAV-HIF-1α. Rats were treated with DI or saline. Neurological scores and infarction rates were assessed. I/R damage was examined by HE, 2,3,5-triphenyltetrazolium and Nissl stainings. Expression levels of relative proteins [TNF-α, IL-6, IL-1ß, SOD, MDA, ROS, HIF-1α, CXC chemokine receptor 4 (CXCR4) and NF-κB] were measured. DI treatment improved neurological scores and reduced infarction rates, suggesting that it inhibits inflammation and oxidative stress. The expression levels of HIF-1α, CXCR4 and NF-κB were decreased. However, the effectiveness of DI on inflammation inhibition was lost after HIF-1α overexpression. DI may directly target HIF-1α to suppress neuroinflammation and reduce I/R injury by suppressing the HIF-1α/CXCR4/NF-κB signaling pathway.
Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit , NF-kappa B , Neuroinflammatory Diseases , Rats, Sprague-Dawley , Receptors, CXCR4 , Reperfusion Injury , Salvia miltiorrhiza , Signal Transduction , Animals , Receptors, CXCR4/metabolism , Reperfusion Injury/metabolism , Reperfusion Injury/drug therapy , NF-kappa B/metabolism , Signal Transduction/drug effects , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Male , Rats , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Infarction, Middle Cerebral Artery/metabolism , Infarction, Middle Cerebral Artery/drug therapy , Brain Ischemia/metabolism , Brain Ischemia/drug therapyABSTRACT
The title compound, C18H22N2O5, was synthesized by nitrification of its enol precursor. The pyrrolidine ring plane adopts a twisted conformation about the C-C bond linking the spiro centre and the C=O group remote from the N atom. It makes dihedral angles of 71.69â (9) and 88.92â (9)°, respectively, with the benzene ring plane and the plane defined by the four C atoms that form the seat of the of the cyclo-hexane chair. At the spiro centre, the NH group is axial and the C=O group is equatorial with respect to the cyclo-hexane ring. In the crystal, inversion dimers linked by pairs of N-Hâ¯O hydrogen bonds generate R 2 (2)(8) loops. The dimers are linked by C-Hâ¯O inter-actions, generating a three-dimensional network.
