Artesunate protects against ischemic stroke through THBS2/CD36/TLR4 pathway.

Area of Science:

• Neuroscience
• Pharmacology
• Biomedical Research

Background:

• Stroke is a leading cause of death and disability with limited treatment options.
• Artesunate (ART), a derivative of artemisinin, possesses anti-inflammatory and neuroprotective properties.
• The precise mechanisms of ART in mitigating ischemic stroke are not fully understood.

Purpose of the Study:

• To investigate the underlying mechanisms of Artesunate (ART) in protecting against experimental ischemic stroke.
• To elucidate ART's role in regulating specific molecular pathways involved in stroke pathology.

Main Methods:

• Utilized transient middle cerebral artery occlusion (tMCAO) mouse models and oxygen-glucose deprivation/reperfusion (OGD/R) cellular models.
• Employed transcriptomic sequencing, molecular docking, cellular thermal shift assay (CETSA), and in vitro experiments.
• Investigated the THBS2/CD36/TLR4 signaling pathway and the effects of THBS2 overexpression.

Main Results:

• ART significantly reduced infarct volume, improved neurological function, and decreased neuronal apoptosis, oxidative stress, and inflammation.
• Transcriptomic analysis identified Thrombospondin 2 (THBS2) as a key target of ART.
• ART demonstrated high affinity for THBS2, inhibited the THBS2/CD36/TLR4 pathway, and attenuated OGD/R-induced damage.

Conclusions:

• Artesunate (ART) exhibits significant neuroprotective effects against experimental ischemic stroke.
• ART exerts its therapeutic benefits by downregulating the THBS2/CD36/TLR4 signaling pathway.
• ART holds potential as a therapeutic agent for ischemic stroke treatment.