Breviscapine regulates lipid metabolism of microglia via the ADORA1/PPARα/ACOX1 pathway to promote spinal cord injury recovery.

Spinal cord injury (SCI) is a disabling disorder with limited therapeutic approaches currently available. The activation of microglia and the consequent dysregulation of lipid metabolism play a crucial role in the pathological process of SCI. Breviscapine (Bre), as a traditional Chinese medicinal extract, has demonstrated potential regulatory effects on lipid metabolism; however, the specific mechanism underlying its role in SCI recovery remains undefined. This study aims to investigate the mechanism through which Bre regulates microglial lipid metabolism via the adenosine A1 receptor (ADORA1)/peroxisome proliferator-activated receptor α (PPARα)/acyl-CoA oxidase 1 (ACOX1) pathway, thereby facilitating SCI recovery. Through the establishment of a mouse model of SCI, we discovered that Bre treatment could significantly improve lipid metabolism in the injured spinal cord area, modulate the inflammatory microenvironment of the spinal cord, and promote the recovery of motor functions in mice. Mechanistic studies revealed that Bre upregulated the expression of ADORA1, which subsequently activated PPARα and its downstream target ACOX1, enhancing lipid metabolism in microglia. This metabolic shift reduced lipid accumulation and inflammatory responses, thereby promoting the formation of a neuroprotective microenvironment. Our research findings Bre in promoting SCI recovery and emphasize the significance of the ADORA1/PPARα/ACOX1 pathway as a potential therapeutic target for SCI.