Improving anti-oxidant stress treatment of subarachnoid hemorrhage through self-assembled nanoparticles of oleanolic acid.

ABSTRACT

Subarachnoid hemorrhage (SAH) is a life-threatening acute hemorrhagic cerebrovascular disease, with early brain injury (EBI) being the main cause of high mortality and severe neurological dysfunction. Oxidative stress plays a crucial role in the pathogenesis of EBI. In this study, we synthesized antioxidant stress nanoparticles based on self-assembled oleanolic acid (OA) using the solvent volatilization method. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) techniques were employed to analyze and understand the self-assembly mechanism of oleic acid nanoparticles (OA NPs). The TUNEL assay, Nissl staining, and brain water content measurements were conducted to investigate the impact of OA NPs on cortical neuronal injury. Additionally, Western blot analysis was performed to investigate the antioxidant stress mechanism of OA NPs. The result showed that OA NPs exhibited a spherical structure with an average diameter of 168 nm. The application of OA NPs in SAH has been found to contribute to the reduction of keap1 protein levels and an increase in the nuclear level of Nrf2. As a result, the transcription of antioxidant stress proteins, including HO1 and NQO1, is triggered. The activation of the antioxidant stress pathway by OA NPs ultimately leads to a decrease in neuron damage and an improvement in neurological dysfunction. In conclusion, we successfully designed and synthesized OA NPs that can efficiently target the site of SAH. These nanoparticles have demonstrated their potential as antioxidants for the treatment of SAH, offering significant clinical applications.