Precision clinical medicine · 2025
Drug pair-derived synergistic therapy of flavonoids luteolin and astragaloside IV promotes neural repair following spinal cord injury via antioxidant and neuroprotective effects.
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Lin Wei, Zhang Peng, Liu Defeng, Feng Yihui, Su Dongdong, Sun Xin, Yuan Na, Zhou Xin, Liu Zhen, Liu Shen, Gao Huiqian, Li Liming, Wang Wenzhao, Tian Ting, Zheng Jihui
Аннотация
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.
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.