Astragaloside IV ameliorates spinal cord injury through controlling ferroptosis in H2O2-damaged PC12 cells in vitro

Ann Transl Med, 2022 · DOI: 10.21037/atm-22-5196 · Published: November 1, 2022

Spinal Cord Injury Pharmacology Genetics

Simple Explanation

Spinal cord injury (SCI) can lead to paralysis and fatality. Ferroptosis, a form of cell death, is involved in SCI. Astragaloside IV (AS-IV), from Astragalus membranaceus, may help motor function recovery in SCI. This study explores AS-IV's effects on PC12 cells damaged by H2O2. The study used cell viability assays and flow cytometry to assess how AS-IV, FIN56 (a ferroptosis inducer), and TFEB siRNA affect PC12 cells injured by H2O2. They also measured caspase-3 and LDH levels, ROS, and analyzed cell structures using electron microscopy and Western blot to examine protein expression. The study found that AS-IV promotes cell growth, reduces apoptosis, and lowers ROS and LDH levels in damaged PC12 cells. AS-IV also increases TFEB expression. Blocking TFEB with siRNA reversed AS-IV's benefits, and FIN56 further enhanced this reversal.

Study Duration

Not specified

Participants

PC12 pheochromocytoma cells

Evidence Level

In vitro study

Key Findings

1
AS-IV treatment (1.0 μM for 48 h) significantly increased the viability of PC12 cells and enhanced their proliferation.
2
AS-IV reduced ROS production and reversed mitochondrial morphology changes in H2O2-treated PC12 cells, suggesting it inhibits ferroptosis.
3
Knockdown of TFEB reversed the protective effects of AS-IV, while FIN56 enhanced the effects of si-TFEB, indicating that TFEB-mediated ferroptosis is involved in H2O2-induced cell injury.

Research Summary

This study investigated the potential of Astragaloside IV (AS-IV) to alleviate spinal cord injury (SCI) by controlling ferroptosis in H2O2-damaged PC12 cells in vitro. The results indicated that AS-IV promotes cell proliferation and inhibits apoptosis in the SCI cell model. AS-IV was found to enhance TFEB expression in H2O2-damaged PC12 cells. Furthermore, AS-IV-mediated expression of TFEB was remarkably attenuated by TFEB knockdown, indicating the importance of the TFEB pathway. The findings suggest that AS-IV can protect PC12 cells against oxidative injury mediated by H2O2 via expression of TFEB and the subsequent suppression of ferroptosis, potentially serving as a clinical treatment for SCI.

Practical Implications

Potential Therapeutic Target

Ferroptosis may represent a potential therapeutic target for SCI, and AS-IV can be further explored for its role in preventing ferroptosis.

Drug Development

AS-IV derivatives with high water solubility and bioavailability could be developed for clinical applications.

Further Research

More in-depth research, development and utilization of AS-IV are required.

Study Limitations

1
The study was conducted in vitro using PC12 cells, which may not fully represent the complex in vivo environment of SCI.
2
The clinical development and promotion of AS-IV has been stagnant due to the low output of astragalus and the difficulty in chemical synthesis, leading to a lack of clinical data support.
3
The specific mechanisms of TFEB in ferroptosis of SCI were not fully elucidated.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury