Ginsenoside Rg1 regulates astrocytes to promote angiogenesis in spinal cord injury via the JAK2/STAT3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng C. A. Mey) is a common traditional Chinese medicine used for anti-inflammation, anti-apoptosis, anti-oxidative stress, and neuroprotection. Ginsenosides Rg1, the main active components isolated from ginseng, may be a feasible therapy for spinal cord injury (SCI). AIMS OF THE STUDY: SCI causes endothelial cell death and blood vessel rupture, ultimately resulting in long-term neurological impairment. As a result, encouraging spinal angiogenesis may be a feasible therapy for SCI. This investigation aimed to validate the capacity of ginsenoside Rg1 in stimulating angiogenesis within the spinal cord. MATERIALS AND METHODS: Rats with SCI were injected intraperitoneally with ginsenoside Rg1. The effectiveness of ginsenoside Rg1 was assessed using the motor function score and the motor-evoked potential (MEP). Immunofluorescence techniques were applied to identify the spinal cord's angiogenesis. Angiogenic factors were examined through Western Blot (WB) and Immunohistochemistry. Oxygen-glucose deprivation (OGD) was employed to establish the hypoxia-ischemia model in vitro, and astrocytes (As) were given ginsenoside Rg1 and co-cultured with spinal cord microvascular endothelial cells (SCMECs). Immunofluorescence, wound healing test, and tube formation assay were used to identify the co-cultured SCMECs' activity. Finally, network pharmacology analysis and siRNA transfection were applied to verify the mechanism of ginsenoside Rg1 promoting angiogenesis. RESULTS: The rats with SCI treated with ginsenoside Rg1 indicated more significant functional recovery, more pronounced angiogenesis, and higher levels of angiogenic factor expression. In vitro, the co-culture system with ginsenoside Rg1 intervention improved SCMECs' capacity for proliferating, migrating, and forming tubes, possibly by promoting the expression of vascular endothelial growth factor (VEGF) in As via the janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. CONCLUSION: Ginsenoside Rg1 can regulate As to promote angiogenesis, which may help to understand the mechanism of promoting SCI recovery.

Ginsenoside Rg1 promotes astrocyte-to-neuron transdifferentiation in rat and its possible mechanism.

INTRODUCTION: Neuronal loss caused by spinal cord injury (SCI) usually contributes to irreversible motor dysfunction. Promoting neuronal regeneration and functional recovery is vital to the repair of SCI. AIMS: Astrocytes, activated by SCI with high proliferative capacity and proximity to neuronal lineage, are considered ideal cells for neuronal regeneration. As previous studies identified several small molecules for the induction of astrocyte-to-neuron, we confirmed that ginsenoside Rg1, a neuroprotective herb, could promote the direct transdifferentiation of astrocyte-to-neuron in rat. METHODS AND RESULTS: Immunofluorescence staining showed that 26.0 ± 1.5% of the induced cells exhibited less astroglial properties and more neuronal markers with typical neuronal morphologies, reflecting 20.6 ± 0.9% of cholinergic neurons and 22.3 ± 1.9% of dopaminergic neurons. Western blot and qRT-PCR revealed that the induced cells had better antiapoptotic ability and Rg1-promoted neuronal transdifferentiation of reactive astrocytes might take effect through suppressing Notch/Stat3 signal pathway. In vivo, a revised SCI model treated by Rg1 was confirmed with faster functional recovery and less injury lesion cavity. CONCLUSION: In summary, our study provided a novel strategy of direct transdifferentiation of endogenous rat reactive astrocytes into neurons with Rg1 and promotion of neuronal regeneration after SCI.