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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings confirm Lut-AST\u2019s therapeutic efficacy in mitigating post-SCI oxidative stress and unveil novel insights into traditional Chinese medicine\u2019s 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/pcmedi\/pbaf037","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T13:02:30Z","timestamp":1766062950000},"source":"Crossref","is-referenced-by-count":7,"title":["Drug pair-derived synergistic therapy of flavonoids luteolin and astragaloside IV promotes neural repair following spinal cord injury via antioxidant and neuroprotective effects"],"prefix":"10.1093","volume":"9","author":[{"given":"Wei","family":"Lin","sequence":"first","affiliation":[{"name":"Traditional Chinese Medicine-Western Medicine Hospital of Cangzhou Department of Orthopedics, , Cangzhou 061001 ,","place":["China"]},{"name":"Hebei Key Laboratory of Integrated Traditional and Western Medicine in Osteoarthrosis Research , Cangzhou 061001 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Medicine-Western Medicine Hospital of Cangzhou Department of Orthopedics, , Cangzhou 061001 ,","place":["China"]},{"name":"Hebei Key Laboratory of Integrated Traditional and Western Medicine in Osteoarthrosis Research , Cangzhou 061001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen","family":"Liu","sequence":"additional","affiliation":[{"name":"International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Tianjin Medical University General Hospital Department of Orthopedics, , Tianjin 300052 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqian","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences , Qingdao 266113 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