Borneol-loaded liposomes modified with 5-hydroxy-1H-pyrazole-3-carboxylic acid enhance neuroprotection and brain specific for ischemic stroke therapy.
L’essentiel
Ischemic stroke is a cardiovascular and cerebrovascular disease with high mortality and disability rates, characterized by complex pathophysiological mechanisms. In this study, 5-hydroxy-1H-pyrazole-3-carboxylic acid compound (3g) was identified to possess excellent radical scavenging ability and neuroprotective effect in the oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cell model, as well as chelating effect on Fe3+. To improve the BBB permeability of compound 3g, 3g-borneol co-loaded liposomes (3g-BO-Lips) were prepared using the solvent injection method. 3g-BO-Lips reduced the OGD/R-induced ROS level in SH-SY5Y cells and restored the mitochondrial membrane potential. The imaging experiments confirmed that 3g-BO-Lips had brain-specific property and could accumulate in the ischemic area in middle cerebral artery occlusion/reperfusion (MCAO/R) mice model. In vivo pharmacodynamic studies revealed that 3g-BO-Lips significantly reduced infarct volume, suppressed inflammatory responses, restored behavioral and cognitive abilities in MCAO/R mice. These findings indicate that 3g-BO-Lips possesses the potential to target ischemic brain regions, exhibiting significant therapeutic efficacy in cerebral ischemia treatment with promising application prospects.
Synthèse détaillée
Résumé original
Ischemic stroke is a cardiovascular and cerebrovascular disease with high mortality and disability rates, characterized by complex pathophysiological mechanisms. In this study, 5-hydroxy-1H-pyrazole-3-carboxylic acid compound (3g) was identified to possess excellent radical scavenging ability and neuroprotective effect in the oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cell model, as well as chelating effect on Fe3+. To improve the BBB permeability of compound 3g, 3g-borneol co-loaded liposomes (3g-BO-Lips) were prepared using the solvent injection method. 3g-BO-Lips reduced the OGD/R-induced ROS level in SH-SY5Y cells and restored the mitochondrial membrane potential. The imaging experiments confirmed that 3g-BO-Lips had brain-specific property and could accumulate in the ischemic area in middle cerebral artery occlusion/reperfusion (MCAO/R) mice model. In vivo pharmacodynamic studies revealed that 3g-BO-Lips significantly reduced infarct volume, suppressed inflammatory responses, restored behavioral and cognitive abilities in MCAO/R mice. These findings indicate that 3g-BO-Lips possesses the potential to target ischemic brain regions, exhibiting significant therapeutic efficacy in cerebral ischemia treatment with promising application prospects.