Astragaloside IV Alleviates Brain Injury Induced by Hypoxia via the Calpain-1 Signaling Pathway

by Selleckchem | Jun 07 2023

Long-term hypoxia can induce oxidative stress and apoptosis in hippocampal neurons that can lead to brain injury diseases. Astragaloside IV (AS-IV) is widely used in the antiapoptotic therapy of brain injury diseases. However, its mechanism of action is still not fully understood. In this study, we investigated the effect of AS-IV on hypoxia-induced oxidative stress and apoptosis in hippocampal neurons and explored its possible mechanism. In vivo, mice were placed in a hypoxic circulatory device containing 10% O2 and gavaged with AS-IV (60 and 120 mg/kg/d) for 4 weeks. In vitro, mouse hippocampal neuronal cells (HT22) were treated with hypoxia (1% O2) for 24 hours in the presence or absence of AS-IV, MDL-28170 (calpain-1 inhibitor), or YC-1 (HIF-1α inhibitor). The protective effect of AS-IV on brain injury was further explored by examining calpain-1 knockout mice. The results showed that hypoxia induced damage to hippocampal neurons, impaired spatial learning and memory abilities, and increased oxidative stress and apoptosis. Treatment with AS-IV or calpain-1 knockout improved the damage to hippocampal neurons and spatial learning and memory, attenuated oxidative stress and inhibited cell apoptosis. These changes were verified in HT22 cells. Overexpression of calpain-1 abolished the improvement of AS-IV on apoptosis and oxidative stress. In addition, the effects of AS-IV were accompanied by decreased calpain-1 and HIF-1α expression, and YC-1 showed a similar effect as AS-IV on calpain-1 and caspase-3 expression. In conclusion, this study demonstrates that AS-IV can downregulate the calpain-1/HIF-1α/caspase-3 pathway and inhibit oxidative stress and apoptosis of hippocampal neurons induced by hypoxia, which provides new ideas for studying the antiapoptotic activity of AS-IV.

Comments:

In this study, the researchers investigated the mechanism of action of Astragaloside IV (AS-IV) in protecting against hypoxia-induced oxidative stress and apoptosis in hippocampal neurons. They used both in vivo and in vitro methods to study the effects of AS-IV on mice and hippocampal neuronal cells (HT22), respectively.

The results showed that hypoxia led to damage to hippocampal neurons, impaired spatial learning and memory abilities, and increased oxidative stress and apoptosis. However, treatment with AS-IV or calpain-1 knockout improved the damage to hippocampal neurons and spatial learning and memory, attenuated oxidative stress and inhibited cell apoptosis. The researchers also found that the effects of AS-IV were accompanied by decreased expression of calpain-1 and HIF-1α, and that YC-1, a HIF-1α inhibitor, had a similar effect as AS-IV on calpain-1 and caspase-3 expression.

Based on these findings, the researchers concluded that AS-IV can downregulate the calpain-1/HIF-1α/caspase-3 pathway and inhibit oxidative stress and apoptosis of hippocampal neurons induced by hypoxia. This study provides new insights into the antiapoptotic activity of AS-IV and may have implications for the development of therapies for brain injury diseases.