Ginsenoside Rg1 Reduces Brain Damage from Stroke by Blocking Cell Self-Digestion

Jim Crocker
28th June, 2024

Ginsenoside Rg1 Reduces Brain Damage from Stroke by Blocking Cell Self-Digestion

Image Source: Natural Science News, 2024

Key Findings

  • Researchers at Shanghai University of Traditional Chinese Medicine found that Ginsenoside Rg1 (Rg1) can protect against brain damage caused by restoring blood flow after a stroke
  • Rg1 works by inhibiting autophagy, a process that can worsen brain injury if excessive, through multiple steps including blocking autophagy initiation and causing lysosomal dysfunction
  • The protective effects of Rg1 are mediated by activating the mTOR signaling pathway, which is crucial for its ability to reduce brain damage during reperfusion
Cerebral ischemia/reperfusion (I/R) injury is a significant challenge in treating stroke patients, often exacerbating the damage caused by the initial lack of blood flow. This injury occurs when blood flow is restored to previously ischemic brain tissue, leading to further neuronal damage. Despite the prevalence of this issue, there are currently no specific pharmaceutical agents or therapeutic interventions that effectively mitigate cerebral I/R injury. A recent study conducted by researchers at Shanghai University of Traditional Chinese Medicine has investigated the potential of Ginsenoside Rg1 (Rg1), a compound derived from Panax ginseng, in protecting against cerebral I/R injury by regulating autophagy[1]. Autophagy is a cellular process that involves the degradation and recycling of cellular components. It plays a crucial role in maintaining cellular homeostasis and has been implicated in the protection of brain tissue during I/R injury. However, excessive autophagy can lead to cell death, contributing to the worsening of cerebral I/R injury. Previous research has highlighted the importance of understanding the mechanisms of neuronal death during ischemic stroke to develop effective neuroprotective interventions[2]. In the study by Shanghai University of Traditional Chinese Medicine, the researchers established both in vitro and in vivo models to investigate the protective effects of Rg1 against I/R injury. They used SK-N-AS and SH-SY5Y cells subjected to oxygen-glucose deprivation (OGD) followed by reperfusion with Rg1 at varying concentrations. Additionally, middle cerebral artery occlusion (MCAO) mice were injected with Rg1 for three days before and on the day of surgery. The results demonstrated that Rg1 treatment significantly mitigated I/R injury in both models. The study found that the induction of autophagy contributed to I/R injury, and Rg1 effectively inhibited this process. Rg1 impeded autophagy initiation, induced lysosomal dysfunction, and inhibited cathepsin enzyme activities. These findings suggest that Rg1 exerts its protective effects by inhibiting autophagy through multiple steps. Furthermore, the researchers identified that the activation of the mTOR signaling pathway was pivotal in mediating the inhibitory effect of Rg1 on autophagy. Treatment with Torin-1, an autophagy inducer and mTOR-specific inhibitor, significantly reversed the impact of Rg1 on autophagy, thereby decreasing its protective efficacy against I/R injury. This study builds on previous findings that have explored the mechanisms of neuronal death during ischemic stroke. For instance, it has been shown that increased hydrogen peroxide (H2O2) generation is involved in hypoxia-ischemia (HI)-mediated neonatal brain injury, with the hydroxyl radical playing a significant role in this process[3]. The current study's focus on autophagy provides a new perspective on the molecular mechanisms underlying I/R injury and highlights the potential of targeting autophagy as a therapeutic strategy. The findings from this study also align with the need for rapid and effective interventions in stroke treatment. Previous research has emphasized the importance of timely reperfusion therapies, such as intravenous thrombolytic therapy (IVT) and endovascular thrombectomy (EVT), in improving long-term functional outcomes and reducing mortality in stroke patients[4]. However, these treatments can also lead to reperfusion injury, underscoring the need for additional protective strategies. Moreover, the study's results are consistent with observations of reperfusion injury in stroke patients undergoing mechanical thrombectomy. Radiological observed reperfusion injury (RORI) has been identified as a frequent occurrence in these patients and is associated with poor neurological outcomes despite successful recanalization[5]. The protective effects of Rg1 against I/R injury could potentially address this issue by providing a means to mitigate the detrimental effects of reperfusion. In conclusion, the study conducted by Shanghai University of Traditional Chinese Medicine suggests that Ginsenoside Rg1 may serve as a promising drug candidate for protecting against cerebral I/R injury by inhibiting autophagy through the activation of mTOR signaling. This research not only advances our understanding of the molecular mechanisms involved in I/R injury but also highlights the potential of Rg1 as a therapeutic intervention to improve outcomes for stroke patients.

MedicineHealthBiochem

References

Main Study

1) Ginsenoside Rg1 mitigates cerebral ischaemia/reperfusion injury in mice by inhibiting autophagy through activation of mTOR signalling.

Published 27th June, 2024

https://doi.org/10.1038/s41401-024-01334-4

Related Studies

2) Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications.

https://doi.org/10.1002/med.21817

3) Nitric oxide induces hypoxia ischemic injury in the neonatal brain via the disruption of neuronal iron metabolism.

https://doi.org/10.1016/j.redox.2015.06.007

4) Shorter Door-to-Needle Times Are Associated With Better Outcomes After Intravenous Thrombolytic Therapy and Endovascular Thrombectomy for Acute Ischemic Stroke.

https://doi.org/10.1161/CIRCULATIONAHA.123.064053

5) Reperfusion Injury Is Associated With Poor Outcome in Patients With Recanalization After Thrombectomy.

https://doi.org/10.1161/STROKEAHA.122.039337


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