Anti-Inflammatory Treatment of Subarachnoid Hemorrhage by Self-Assembled Silymarin Nanoparticles

Subarachnoid hemorrhage (SAH) is a common hemorrhagic cerebrovascular disease with high disability rate and high mortality. Early brain injury (EBI) is the main cause of high mortality and delayed neurological dysfunction in patients with SAH. Neuroinflammation is the important pathological processes of EBI.We prepared Silymarin nanoparticles (SIM NPs) through the solvent precipitation method and investigated their role in combating EBI following SAH in mice. We found that SIM NPs with a diameter of 150 nm have the strongest ability to cross the blood-brain barrier. SIM nanoparticles are spherical and contain irregular particles inside, which may be composed mainly of silibinin and assembled through hydrogen bonding. Further in vivo experiments showed that SIM NPs improved short-term neurological dysfunction in SAH mice, reduced cortical neural damage, and reduced EBI inflammation through the Nrf2/STING pathway. Finally, water maze experiments showed that SIM NPs can improve long-term memory and learning ability in SAH mice. Based on the above results, we conclude that silymarin nanoparticles can reduce EBI after SAH by inhibiting the Nrf2/STING pathway, inhibiting neuroinflammation and M1 polarization of microglia.