Protocatechuic aldehyde promotes the functional recovery of spinal cord injury by activating the Wnt/β-catenin signaling pathway

Context/objective: This study aimed to explore the anti-inflammatory and neuroprotective effects of protocatechuic aldehyde (PCA) in rats with spinal cord injury (SCI) and to clarify the molecular mechanisms underlying its pharmacological effects.

Design: Male Sprague Dawley rat model of moderate spinal cord contusion were established.

Setting: Third-class first-class hospital.

Outcome measures: The Basso, Beattie, and Bresnahan scores and performance on the inclined plane test were evaluated. Histological analyses were performed via hematoxylin and eosin staining. Apoptosis in the spinal cord and neurons was detected by 5 terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling staining. Apoptotic factors (Bax, Bcl-2, and cleaved Caspase-3) were also evaluated. iNOS, IL-1β, IL-10, TNF-α, Wnt-3α, β-catenin, iBA-1, and NeuN were assessed by real-time reverse transcription-polymerase chain reaction (RT-PCR), western blotting (WB), and enzyme-linked immunosorbent assay. Cell viability and the immunofluorescence of IL-1β were measured in PC-12 cells.

Results: Using WB and quantitative reverse transcription-PCR, we confirmed that PCA treatment activated the Wnt/β-catenin signaling axis in vivo and in vitro. Hematoxylin and eosin staining and hindlimb motor functional evaluation revealed that treatment with PCA improved tissue protection and functional recovery via the Wnt/β-catenin axis. The upregulation of TUNEL-positive cells, downregulation of neurons, elevated apoptosis-associated factors in rats, and increased apoptotic rates were observed in microglia and PC-12 after PCA application. Finally, PCA mitigated SCI-induced inflammation by targeting the Wnt/β-catenin axis.

Conclusion: This study provided preliminary evidence that PCA inhibits neuroinflammation and Apoptosis through the Wnt/β-catenin pathway, thereby attenuating the secondary injury after SCI and promoting the regeneration of injured spinal tissues.

Protocatechuic aldehyde; Spinal cord injury; Wnt/β-catenin.