Astragaloside IV Enhances Mitophagy to Alleviate Renal Ischemia/Reperfusion Injury via PINK1 /Parkin Pathway

Astragaloside IV (AS‐IV), a primary bioactive component of Astragalus membranaceus (AM). It is very effective in regulating renal diseases. However, the possible underlying mechanism of AS‐IV on renoprotection remains unclear. The aim of this study is to find out the regulation mechanism of AS‐IV on ischemia/reperfusion injury‐induced Acute kidney injury (IRI‐AKI). At first, AS‐IV was confirmed to significantly alleviate renal dysfunction, inflammation, and renal tubular epithelial cell apoptosis in IRI‐AKI mice. Then, it was found that AS‐IV alleviated mitochondrial dysfunction and renal tubular epithelial cell injury induced by IRI. Growing evidence has suggested that PINK1/Parkin‐mediated mitophagy plays a critical protective role in IRI. Based on this, we hypothesized that AS‐IV might exert renoprotective effects through activating the PINK1/Parkin mitophagy pathway. After 3‐MA inhibition of autophagy, AS‐IV no longer showed its protective effect on HK‐2 cells in a hypoxic environment. Through further molecular docking, cell thermal migration, and gene targeted silencing experiments, we confirmed that AS‐IV activates the PINK1/Parkin mitophagy pathway and ultimately alleviates IRI‐AKI. In summary, all these comprehensive experimental findings indicated that AS‐IV can be used as a functional food for the prevention of renal ischemia/reperfusion injury.