Yan Zhang,Xin-yue Zhao,Meng-ting Liu,Zhu-chen Zhou,Hui-bin Cheng,Xu-hong Jiang,Yan-rong Zheng,Zhong Chen
Objective Treating peripheral nerve injury (PNI) presents a clinical challenge due to limited axon regeneration. Strychni Semen, a traditional Chinese medicine, is clinically used for numbness and hemiplegia. However, its role in promoting functional recovery after PNI and the related mechanisms have not yet been systematically studied. Methods A mouse model of sciatic nerve crush (SNC) injury was established and the mice received drug treatment via intragastric gavage, followed by behavioral assessments (adhesive removal test, hot-plate test and Von Frey test). Transcriptomic analyses were performed to examine gene expression in the dorsal root ganglia (DRGs) from the third to the sixth lumbar vertebrae, so as to identify the significantly differentially expressed genes. Immunofluorescence staining was used to assess the expression levels of superior cervical ganglia neural-specific 10 protein (SCG10). The ultra-trace protein detection technique was used to evaluate changes in gene expression levels. Results Strychni Semen and its active compounds (brucine and strychnine) improved functional recovery in mice following SNC injury. Transcriptomic data indicated that Strychni Semen and its active compounds initiated transcriptional reprogramming that impacted cellular morphology and extracellular matrix remodeling in DRGs after SNC, suggesting potential roles in promoting axon regeneration. Imaging data further confirmed that Strychni Semen and its active compounds facilitated axon regrowth in SNC-injured mice. By integrating protein–protein interaction predictions, ultra-trace protein detection, and molecular docking analysis, we identified myeloperoxidase as a potentially critical factor in the axon regenerative effects conferred by Strychni Semen and its active compounds. Conclusion Strychni Semen and its active compounds enhance sensory function by promoting axonal regeneration after PNI. These findings establish a foundation for the future applications of Strychni Semen and highlight novel therapeutic strategies and drug targets for axon regeneration. Please cite this article as: Zhang Y, Zhao XY, Liu MT, Zhou ZC, Cheng HB, Jiang XH, Zheng YR, Chen Z. Strychni Semen and its active compounds promote axon regeneration following peripheral nerve injury by suppressing myeloperoxidase in the dorsal root ganglia. J Integr Med . 2025; Epub ahead of print.
Introduction Vascular dementia (VaD) is a cognitive disorder caused by cerebrovascular lesions, often accompanied by secondary axonal damage. Given the high energy-consuming nature of neurons, efficient mitochondrial transport is essential for providing sufficient energy for axonal regrowth. However, developing drugs that effectively modulate mitochondrial transport and support axonal regeneration following VaD remains a challenge. Methods Bilateral carotid artery stenosis (BCAS) was induced in mice, and cognitive function was assessed using the Morris water maze test. Axonal regeneration was quantified via anterograde viral tracing and immunofluorescence. The oxygen-glucose deprivation (OGD) model was established in primary cortical neurons. Axonal elongation and mitochondrial motility were evaluated using live-cell imaging. Western blotting and molecular docking techniques were applied to decipher the molecular mechanisms. Results Our study found that Strychni Semen and its active compound, strychnine (but not brucine), improved cognitive function and promoted axonal regeneration in mice subjected to BCAS. Strychnine promotes post-OGD axonal mitochondrial transport, and inhibiting mitochondrial transport blocks its axon regeneration-promoting effects. Moreover, strychnine augmented the translocation of several transporter proteins to mitochondria. Molecular docking studies further indicate that the proteins DISC1 and FEZ1 may play pivotal roles in strychnine-induced mitochondrial transport. Discussion This study provides preliminary evidence supporting the therapeutic potential of Strychni Semen and its active compound, strychnine, in axonal regeneration and VaD, although the underlying molecular machinery requires further elucidation. Conclusion Our results indicate that Strychni Semen and its active compound, strychnine, encourage axonal regeneration following VaD in mice by enhancing axonal mitochondrial transport.
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