Repairing Effect of Ginsenoside Rh2 on Motor Function After Spinal Cord Injury
Introduction
Spinal cord injury (SCI) can lead to severe impairments in motor, sensory, and autonomic nervous system functions. It has been reported that motor function recovery can be promoted by mediating neuroinflammation as well as programmed cell death such as autophagy and pyroptosis. Strikingly, ginsenoside Rh2 (GRh-2), a kind of representative rare ginsenosides extracted from Panax ginseng, has been revealed to improve motor function and alleviate inflammation after SCI.
About SCI
SCI is a severe central nervous system disorder involving irreversible neural and multiple organ system damage, with a high incidence, high cost, a high disability rate and a low age of onset. SCI can be caused by high-intensity injuries, such as traffic accidents, falling injuries and violent injuries, or by infections, tumors, vertebral column degenerative disorders, ischemia-reperfusion injuries, and vascular causes. Given the complex pathological mechanisms and the difficulties of neural regeneration in the central nervous system, the treatment of SCI faces many challenges, and there is currently no targeted or highly effective approach to curing SCI.
| Categories of SCI | Manifestations |
| Primary injury | The directly disrupted structural integrity of neurons and nerve fibers within the spinal cord; the interruption of spinal cord continuity. |
| Secondary injury | Inflammation; tissue ischemia; imbalance in ion homeostasis, autophagy, pyroptosis, and cell apoptosis |
Restoration of motor function in SCI mice post treatment of GRh-2
GRh2 improves functional recovery after SCI, as indicated by lower hindlimb dragging ratio as well as higher BMS scores and inclined plane angles in the SCI + GRh2 group than in other groups. Meanwhile, SCI mice treated with GRh-2 present reduced glial scar area in the mouse spinal cord tissues as well as significantly increased MAP2 expression, SYN-positive synapse counts, and anterior horn neurons in the SCI + 30 mg/kg GRh2 group than in the other groups. All of these findings hint the recovery of motor function in SCI mice following treatment of GRh-2. Notably, no marked changes are viewed in terms of the hepatic and renal function or body weight of SCI mice, showing favorable safety of GRh-2.
The association between autophagy and pyroptosis after SCI
Promoting autophagy may be crucial for the functional recovery after SCI. Specifically, SCI mice show a deficiency in autophagic flux which can exacerbate neuroinflammation and motor deficits. Importantly, GRh-2 can increase the autophagic flux to recover motor function.
Also, GRh-2 inhibits pyroptosis after SCI, as evidenced by the reduction in the expression levels of pyroptosis-related markers in the SCI + GRh2 group compared to the SCI group, in terms of both the integrated density in neurons and the number of positive microglial cells. Remarkably, pyroptosis is a solubilizing and inflammatory form of programmed cell death, and excessive pyroptosis can lead to severe inflammatory reactions in the body, which further exacerbates secondary injury of SCI.
Moreover, GRh2 inhibits pyroptosis by enhancing autophagy after SCI. The effect of GRh2 on the upregulation of autophagic flux and activation of the autophagy lysosome pathway is partially blocked by 3-methyladenine (3-MA), an autophagy inhibitor.
Also, GRh-2 inhibits pyroptosis after SCI, as evidenced by the reduction in the expression levels of pyroptosis-related markers in the SCI + GRh2 group compared to the SCI group, in terms of both the integrated density in neurons and the number of positive microglial cells. Remarkably, pyroptosis is a solubilizing and inflammatory form of programmed cell death, and excessive pyroptosis can lead to severe inflammatory reactions in the body, which further exacerbates secondary injury of SCI.
Moreover, GRh2 inhibits pyroptosis by enhancing autophagy after SCI. The effect of GRh2 on the upregulation of autophagic flux and activation of the autophagy lysosome pathway is partially blocked by 3-methyladenine (3-MA), an autophagy inhibitor.
Conclusion
GRh2 enhances autophagy and suppresses pyroptosis to facilitate the recovery of motor function and suppress the inflammation after SCI, showing potential clinical applicability in addressing secondary injury of SCI.
Reference
Liu R, Jiang L, Chen Y, et al. Ginsenoside-Rh2 Promotes Functional Recovery after Spinal Cord Injury by Enhancing TFEB-Mediated Autophagy. J Agric Food Chem. 2024;72(26):14727-14746. doi:10.1021/acs.jafc.4c02379
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