Abstract
Cerebral ischemia-reperfusion injury significantly contributes to global morbidity and mortality. Loganin is a natural product with various neuroprotective effects; however, it lacks targeted specificity for particular cells or receptors, which may result in reduced therapeutic efficacy and an increased risk of side effects. To address the limitations of loganin, we developed LA-1, a novel compound incorporating an Arg-Gly-Asp (RGD) peptide to target integrin receptor αvβ3, enhancing brain-targeting efficacy. LA-1 exhibited optimal nanoscale properties, significantly improved cell viability, reduced ROS production, and enhanced survival rates in vitro. In vivo, LA-1 decreased infarct sizes, improved neurological function, and reduced oxidative stress and neuroinflammation. Proteomic analysis showed LA-1 modulates PI3K/Akt and Nrf2/HO-1 pathways, providing targeted neuroprotection. These findings suggest LA-1's potential for clinical applications in treating cerebral ischemia-reperfusion injury.