Synergistic drug pair shows promise for spinal cord injury recovery

Spinal cord injury remains one of the most challenging neurological conditions to treat, largely because damage continues to worsen long after the initial trauma. Secondary injury processes—driven by excessive reactive oxygen species, inflammation, and cell death—create a hostile microenvironment that blocks neural regeneration. Current clinical strategies focus on surgery, rehabilitation, and limited pharmacological interventions, yet long-term functional recovery is often minimal. Many experimental therapies fail because they target only one aspect of this complex pathology. As growing evidence suggests that multi-target regulation is essential for meaningful repair, there is an urgent need to explore therapeutic strategies capable of simultaneously modulating oxidative stress, inflammation, and neural regeneration.

In a study published (DOI: 10.1093/pcmedi/pbaf037) on December 18, 2025, in Precision Clinical Medicine, researchers from the University of Health and Rehabilitation Sciences, Tianjin Medical University General Hospital, and Shandong University investigated whether a synergistic drug-pair approach could improve recovery after severe spinal cord injury. Using both oxidative stress-induced neuronal cell models and a rat spinal cord injury model, the team evaluated the combined effects of luteolin and astragaloside IV—two bioactive compounds derived from traditional herbal medicine. Their findings demonstrate that the dual-compound therapy significantly enhances neural repair and functional recovery by simultaneously reducing oxidative stress and neuroinflammation.

The researchers first tested the luteolin-astragaloside IV combination in a cellular model designed to mimic oxidative stress-induced neuronal injury. While each compound alone provided limited protection, their combination significantly reduced reactive oxygen species accumulation and improved cell survival, demonstrating a clear synergistic antioxidant effect.

The team then evaluated the therapy in a rat model of severe spinal cord injury. Animals receiving a single, localized injection of the combined treatment showed progressive improvements in motor function over five weeks, as measured by standardized behavioral tests. These functional gains were accompanied by striking histological changes. The injured spinal cords exhibited reduced tissue cavitation, smaller lesion areas, and improved structural integrity.

Further analysis revealed that the combined treatment suppressed excessive activation of microglia and astrocytes—key drivers of post-injury inflammation and glial scar formation—while enhancing the presence of neurofilament-positive nerve fibers and serotonin-related neural pathways. Computational network pharmacology and molecular docking analyses suggested that the therapy acts through multiple interconnected molecular targets involved in oxidative stress regulation, inflammation control, and apoptosis. Together, these findings indicate that the luteolin-astragaloside IV pairing promotes recovery by reshaping the injury microenvironment rather than acting on a single repair mechanism.

"Spinal cord injury is not driven by a single pathological process, so it is unlikely that a single-target drug can achieve meaningful recovery," said one of the study's senior authors. "What makes this strategy compelling is the way these two compounds complement each other—one strongly counteracts oxidative stress, while the other supports neural protection and regeneration. By working together, they create conditions that are far more favorable for repair. This study provides a strong rationale for exploring synergistic, multi-component therapies in the treatment of complex neurological injuries."

The study offers important insights for the future design of spinal cord injury therapies. By demonstrating that a carefully selected drug pair can outperform single-compound treatments, it supports a shift toward multi-target strategies for neurological repair. Although the current findings are based on preclinical models, they lay the groundwork for developing safer, more effective combination therapies that may reduce reliance on high-dose steroids or invasive interventions. Beyond spinal cord injury, this synergistic approach could inform treatment strategies for other neurodegenerative and traumatic conditions where oxidative stress and inflammation play central roles, advancing the broader field of regenerative and precision medicine.