Cyclovirobuxine D Brain-Targeted Liposomes Improve Cerebral Ischemia-Reperfusion Injury via Anti-Oxidant Stress and Activating Autophagy

One of the main issues faced by nervous system diseases is that drugs are difficult to enter the brain. The previous study suggested that Cyclovirobuxine D (CVBD) encapsulated in Angiopep-conjugated Polysorbate 80-Coated Liposomes showed a better brain targeting by intranasal administration. Therefore, this study concentrated on the protection and mechanism of CVBD brain-targeted liposomes in treating CIRI. Middle cerebral artery occlusion-reperfusion induced CIRI model rats to explore the protective effect of CVBD brain-targeted liposome on CIRI. Moreover, the protective effect of CVBD liposomes on OGD/R-injuredIP:HT2cells203.8.109.20wasOn:examinedThu,by28cellJlfusion2022degree,10:29:57cellproliferation curve and cell viabil-ity. OGD/R-injured HT22 cell was infected bmRFP-GFP-LC3 adenovirus. The autophagosome and autophagy flow were Copy right: American Scientific Publishers observed by laser confocal microscopy, and autophagy-related protiexpressions were analyzed by Western blot. The Delivered by Ingen a classic autophagy inhibitor, chloroquine, was used to explore the autophagy-regulated mechanism of CVBD brain-targeted liposomes in treating CIRI. CVBD liposomes increased cell viability and decreased ROS level, improved oxidative stress protein expressions and activated autophagy in vitro. Furthermore, CVBD liposomes reversed the decrease of cell viability, increase of ROS level, and reduction of protein expressions associated with anti-oxidative stress and autophagy induced by chloroquine. Collectively, CVBD liposomes inhibited CIRI via regulating oxidative stress and enhancing autophagy level in vivo and in vitro.