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Electrical stimulation (ES) of the spinal cord is a promising therapy for functional rehabilitation after spinal cord injury (SCI). However, the specific mechanism of action is poorly understood. We designed and applied an implanted ES device in the SCI area in rats and determined the effect of ES on the treatment of motor dysfunction after SCI using behavioral scores. Additionally, we examined the molecular characteristics of the samples using proteomic and transcriptomic sequencing. The differential molecules between groups were identified using statistical analyses. Molecular, network, and pathway-based analyses were used to identify group-specific biological features. ES (0.5 mA, 0.1 ms, 50 Hz) had a positive effect on motor dysfunction and neuronal regeneration in rats after SCI. Six samples (three independent replicates in each group) were used for transcriptome sequencing; we obtained 1026 differential genes, comprising 274 upregulated genes and 752 downregulated genes. A total of 10 samples were obtained: four samples in the ES group and six samples in the SCI group; for the proteome sequencing, 48 differential proteins were identified, including 45 up-regulated and three down-regulated proteins. Combined transcriptomic and proteomic studies have shown that the main enrichment pathway is the hedgehog signaling pathway. Western blot results showed that the expression levels of Sonic hedgehog (SHH) (P

Objective: Spinal cord injury (SCI) often leads to severe physiological and pathological changes in patients. Erxian Decoction (EXD) is effective in the postoperative treatment of spinal cord injury, but its specific mechanism of action is poorly defined. Methods: Network pharmacology and molecular docking were used to predict the potential mechanisms of EXD in SCI. In vivo studies were used to validate the above predictions. For in vivo study, the rats were pretreated with or without EXD (5.76 g/kg, by intragastric gavage). Multiple molecular biological test methods to identify molecular mechanisms. One-way analysis of variance (ANOVA) was used with Bonferroni's post-hoc test to identify the differences between groups. Results: In vivo studies have shown that EXD improved motor function at 7dpi in SCI rats (P < 0.0001), significantly reduced spinal cord edema (P = 0.0139), upregulated 5-HT, GFAP, and TMEM119 expression. Through network pharmacology analysis, we found that Akt1 in EXD plays a role in treating SCI. The underlying mechanism may be the inhibition of apoptosis after activation of Akt1 phosphorylation. Molecular docking revealed that the key compounds could spontaneously bind to the Akt1 protein. Pharmacological inhibition of Akt1 activation by MK-2206, attenuated the anti-apoptotic effect of EXD on SCI in rats (P < 0.0001). Conclusions: EXD inhibits apoptosis by activating Akt1, reduce spinal cord edema and restore behavioral function after SCI in rats.