Protective Effect of Methoxsalen on Spinal Cord Injury in the Rat Model via Regulation of the PI3K/Akt Pathway.

BACKGROUND: Spinal cord injury (SCI) is a major cause of disability, and the management of secondary injury remains challenging. OBJECTIVES: This study evaluated the protective effects of methoxsalen against SCI and investigated its potential mechanism of action. METHODS: Network pharmacology and molecular docking were performed to identify the molecular targets of methoxsalen for the treatment of SCI. SCI was induced in rats by laminectomy, and methoxsalen (12 and 24 mg/kg, p.o.) was administered for 14 days after SCI induction. Motor function was assessed using the Basso, Beattie, and Bresnahan (BBB) score, and spinal cord inflammation was evaluated by assessing water deposition and inflammatory cytokine levels in SCI rats. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to assess the mRNA expression of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) in SCI rats. RESULTS: Molecular docking data showed that methoxsalen interacted with AKT, PI3K, and nuclear factor-κB (NF-κB), with binding energies of -9.1, -9.2, and -9.4 kcal/mol, respectively. The BBB score was significantly improved in the methoxsalen-treated group compared with the SCI group. MDA (18.6 ± 0.9 nmol/mg) and ROS (1.30 ± 0.04-fold) levels were significantly reduced, whereas GSH (92.0 ± 2.2 µM/mg) and SOD (54.2 ± 1.3 U/mg) levels were increased in the methoxsalen-treated group compared with the SCI group. Methoxsalen treatment ameliorated inflammatory alterations and cytokine levels in rats with SCI. The mRNA expression of PI3K, AKT, and NF-κB was attenuated in spinal cord tissue from methoxsalen-treated rats with SCI. CONCLUSIONS: Methoxsalen treatment improved motor function in rats with SCI by modulating the PI3K/AKT signaling pathway.