Astragaloside IV promotes neuronal axon regeneration by inhibiting the PTEN/AKT pathway

Background

Neuronal survival and regeneration are critical aspects of recovery from ischemic brain injuries. Astragaloside IV (AS-IV), a saponin extracted from the traditional Chinese medicine Astragalus membranaceus, has shown promise in promoting neuronal health. This study investigates the effects of AS-IV on neuronal survival and apoptosis post-oxygen-glucose deprivation (OGD), focusing on the modulation of the PTEN/AKT signaling pathway.

Methods

Rat primary neuronal cells were isolated and subjected to OGD to simulate ischemic conditions. Afterwards, cells were treated with low and high doses of AS-IV. Neuronal viability and apoptosis were assessed using MTT and flow cytometry (FCM) assays. Immunofluorescence and Western blot analyses were performed to evaluate the expression of neuronal markers and proteins involved in the PTEN/AKT pathway.

Results

Post-OGD, neuronal cells exhibited decreased viability and increased apoptosis, which were significantly mitigated by AS-IV. Immunofluorescence showed enhanced Tuj1 expression, indicating increased neuronal purity and survival, enhanced NF200 expression, indicating increased axon lengths. FCM results revealed reduced apoptosis rates, particularly with higher doses of AS-IV. Western blot analysis confirmed inhibition of PTEN and activation of AKT, facilitating enhanced neuronal survival and axona regeneration. Additionally, overexpression of PTEN negated the anti-apoptotic effects of AS-IV, underscoring the critical role of the PTEN/AKT pathway in AS-IV mediated neuroprotection.

Conclusion

AS-IV enhances neuronal survival and axona regeneration by modulating the PTEN/AKT pathway, highlighting its potential as a therapeutic agent for ischemic brain injuries. These findings suggest that targeting this pathway could be a strategic focus for developing effective neuroprotective therapies.