# Anti‐Inflammatory Treatment of Subarachnoid Hemorrhage by Self‐Assembled Silymarin Nanoparticles

## TL;DR

This study shows that silymarin nanoparticles can reduce brain inflammation and improve recovery after subarachnoid hemorrhage in mice.

## Contribution

The novel use of self-assembled silymarin nanoparticles to treat neuroinflammation after SAH is introduced.

## Key findings

- Silymarin nanoparticles with 150 nm diameter effectively cross the blood-brain barrier.
- They reduce early brain injury and neuroinflammation via the Nrf2/STING pathway.
- Long-term cognitive improvements were observed in SAH mice treated with the nanoparticles.

## Abstract

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.

Herein, nanoparticles self‐assembled from silymarin have been developed and they are applied in the treatment of neuroinflammation following subarachnoid hemorrhage. The findings reveal that these silymarin nanoparticles can inhibit neuroinflammation through the stimulator of interferon gene/interferon regulatory factor 3 pathway.© 2025 WILEY‐VCH GmbH