Salvianolic acid A ameliorates renal ischemia/reperfusion injury by activating Akt/mTOR/4EBP1 signaling pathway.
Am J Physiol Renal Physiol. 2018 Jan 31. Epub 2018 Jan 31. PMID: 29384417
Salvianolic acid A (Sal A) has been shown to prevent and treat ischemic cardiovascular as well as cerebral vascular diseases. However, little is known about Sal A in renal ischemia/reperfusion (I/R) injury. In this study, a renal I/R injury model in rats and a hypoxia/reoxygenation (H/R) model to damage proximal renal tubular cells (HK-2) were used to assess whether Sal A halts the development and progression of renal I/R injury. As compared to vehicle treatment, Sal A significantly attenuated kidney injury and lowered plasma creatinine, blood urea nitrogen levels, the number of apoptosis-positive tubular cells, and kidney oxidative stress after renal I/R injury. In addition, Sal A also activated phosphorylated-protein kinase B (p-Akt) and phosphorylated-mammalian target of rapamycin (p-mTOR) compared to vehicle-treated I/R injury rats. In H/R injury HK-2 cells, Sal A can reduce the levels of reactive oxygen species (ROS) in a dose-related manner. Sal A also increased the protein expression of phosphorylated-eukaryotic initiation factor 4E binding protein 1 (p-4EBP1) compared to vehicle. Furthermore, the cytoprotective activity of Sal A was inhibited by these two LY294002 and rapamycin. These findings indicate that Sal A may ameliorate renal I/R injury and promote tubular cell survival via the Akt/mTOR/4EBP1pathway and Sal A could be a candidate compound for the prevention of ischemic tissue damage.