Drug pair-derived synergistic therapy of flavonoids luteolin and astragaloside IV promotes neural repair following spinal cord injury via antioxidant and neuroprotective effects.

BACKGROUND

Spinal cord injury (SCI) induces a damaging oxidative microenvironment exacerbating secondary injury. The traditional Chinese medicine (TCM) drug-pair Dangshen and Huangqi, known for antioxidant and neuroprotective effects, yields key components luteolin (Lut) and astragaloside IV (AST), both promising in oxidative stress-related neurological disorders but unexplored in combination for SCI.

METHODS

We investigated the synergistic antioxidant effects of Lut-AST combination therapy using an in vitro oxidative stress model in PC12 cells, and subsequently assessed its neuroprotective efficacy through behavioral assessments and histopathological analyses in a rat model of severe SCI. Finally, we utilized network pharmacology and molecular docking to predict and explore the potential of the Lut-AST drug pair for treating SCI through multi-target therapy.

RESULTS

Our study demonstrated that the Lut-AST drug pair synergistically attenuated oxidative stress-induced cytotoxicity. Lut-AST treatment effectively promoted nerve repair and functional recovery in SCI rats. A significant recovery of motor functions was observed accompanied byh reduced accumulation of reactive oxygen species. Neuroinflammation and glial scars were largely alleviated, while the distribution of 5-hydroxytryptamine and neurofilament-positive nerve fibers was evidently increased.

CONCLUSION

These findings confirm Lut-AST's therapeutic efficacy in mitigating post-SCI oxidative stress and unveil novel insights into traditional Chinese medicine's inherent multi-component synergistic interactions, suggesting potentiated outcomes through integrated antioxidant mechanisms and multi-target regulation. This study provides a paradigm for optimizing TCM-derived neuroprotective strategies by leveraging component synergy, informing novel combinatorial therapies for SCI management.