Trichosanthis peel injection improves functional recovery after spinal cord injury associated with the modulation of neuroinflammation and oxidative stress

INTRODUCTION: Spinal cord injury (SCI) leads to irreversible neurological deficits mainly through inflammation, oxidative stress, and apoptosis. Trichosanthis Peel Injection (TPI), a traditional Chinese medicine with known anti-inflammatory and antioxidant properties, has not yet been evaluated for its therapeutic potential in SCI. OBJECTIVE: To investigate whether TPI promotes functional recovery after SCI and to explore its underlying mechanisms through multi-target analysis. METHODS: A mouse model of SCI was established, and TPI was administered daily for 28 days. Motor recovery was assessed using Basso-Beattie-Bresnahan (BBB) scoring, footprint analysis, and rotarod testing. Lesion size, inflammation, oxidative stress, and apoptosis were analyzed through histology, immunofluorescence, ELISA, qPCR, and western blotting. Network pharmacology and molecular docking were applied to predict key compounds and potential targets. RESULTS: TPI significantly improved locomotor function, reduced lesion size, and attenuated inflammatory responses, as shown by decreased TNF-α, IL-6, and IL-1β expression and enhanced M2 microglial polarization. TPI also decreased ROS and MDA levels while increasing SOD activity and preserving neuronal morphology. Network analysis identified quercetin, luteolin, and kaempferol with potential regulatory roles in TNF signaling pathways. CONCLUSION: TPI promotes functional recovery after SCI, potentially involving coordinated modulation of inflammation, oxidative stress, and apoptosis. These findings highlight the neuroprotective potential of TPI in a mouse model of spinal cord injury, underscoring the need for further translational research.