# Dehydrocostus Lactone Inhibits Microglia‐Mediated Neuroinflammation by Targeting CYP2A6 to Improve Ischemic Brain Injury

## TL;DR

This study shows that dehydrocostus lactone reduces brain inflammation after stroke by targeting a specific enzyme, improving recovery.

## Contribution

DHC is shown to inhibit neuroinflammation via CYP2A6, offering a novel therapeutic strategy for ischemic stroke.

## Key findings

- DHC reduced inflammatory factors and improved neurological deficits in a mouse stroke model.
- CYP2A6 was identified as a key target of DHC in mediating its anti-inflammatory effects.
- Combining DHC with a CYP2A6 inhibitor enhanced its anti-inflammatory impact.

## Abstract

Neuroinflammation is an important factor in ischemic stroke. Dehydrocostus lactone (DHC) plays an anti‐inflammatory role in certain diseases. However, the role of DHC in neuroinflammation after ischemic stroke remains unclear.

DHC was administered to lipopolysaccharide (LPS)‐treated BV2 cells and a middle cerebral artery occlusion (MCAO) model to detect the levels of inflammatory factors using quantitative real‐time PCR, western blotting, and behavioral tests. Morphological changes in microglia were observed using immunofluorescence. The Swiss Target Prediction database was used to predict the target of DHC. Finally, a specific inhibitor of the target protein was used to investigate its potential synergistic role in neuroinflammation, both with and without being combined with DHC.

The expression of inflammation‐related factors both in vivo and in vitro was improved by DHC, and the neurological deficits in mice after MCAO were improved in the DHC administration group. In addition, the Swiss Target Prediction showed that CYP2A6 was a target of DHC. Specifically, the combination of DHC with the CYP2A6 inhibitor showed that DHC exerts anti‐inflammatory effects in a CYP2A6‐dependent manner.

Mechanistically, DHC inhibited neuroinflammation by binding to the target CYP2A6. Our study suggests that DHC is a promising new strategy for treating ischemic stroke.

Dehydrocostus lactone (DHC) inhibits microglia‐mediated neuroinflammation by targeting CYP2A6, reducing the release of pro‐inflammatory factors and improving nerve function impairment, thereby alleviating ischemic brain injury.