Mechanism of Buyang Huanwu Decoction mediating Cav1-regulated Wnt pathway to promote neural regeneration in cerebral ischemic mice

Promoting neural repair after cerebral ischemia (CI) is one of the important intervention strategies. Buyang Huanwu Decoction (BHD) is a traditional Chinese medicine prescription commonly used for the treatment of CI.Previous studies by the research group have shown that BHD can promote neural regeneration after CI. The core cause of motor, sensory, and autonomic dysfunction caused by CI injury is neuronal death. Promoting endogenous neural regeneration is of great significance for neural repair after CI. In this context, the Wnt pathway promotes endogenous neural regeneration worthy of attention. This study aims to elucidate the mechanism by which BHD promotes neural regeneration after CI, focusing on how it mediates caveolin-1 (Cav1) to regulate the Wnt signaling pathway. Using the middle cerebral artery occlusion (MCAO) technique, a CI model was created. To establish the neuroprotective properties of BHD and determine the ideal therapeutic dosage for CI, neurobehavioral scores and pathological alterations were found across several groups of mice after varying doses of BHD were administered. Furthermore, Cav1 knockout (Cav1-/-) mice were used to confirm Cav1's function in BHD-mediated neuronal regeneration following CI. In CI models, BHD was shown to enhance neural regeneration. In vivo research indicate that its mechanism of action is through Cav1 stimulation of the Wnt signaling pathway, which causes related brain-derived trophic factors to be upregulated. This study confirmed, using knockout mice, that BHD promotes nerve regeneration following CI. The results indicate that Cav1 control of the Wnt signaling pathway is likely the mechanism by which this impact is mediated, so offering insights into the possible mechanism of action of BHD and reaffirming Cav1's function in brain regeneration following CI. [Display omitted] •Cav1 is a key target for neural repair regulation after cerebral ischemia.•Neural regeneration after CI is regulated by the Cav1/Wnt/β-catenin axis.•BHD promotes neural regeneration after CI by regulating Cav1/Wnt/β-catenin.