Salvianolic acid A ameliorates renal ischemia/reperfusion injury by activating Akt/mTOR/4EBP1 signaling pathway

Abstract

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 with vehicle treatment, Sal A significantly attenuated kidney injury after renal I/R injury, accompanied by decreases in plasma creatinine, blood urea nitrogen levels, the number of apoptosis-positive tubular cells, and kidney oxidative stress. Sal A also activated phosphorylated protein kinase B (p-Akt) and phosphorylated-mammalian target of rapamycin (p-mTOR) compared with vehicle-treated I/R injury rats. In H/R-injured HK-2 cells, Sal A can reduce the levels of reactive oxygen species in a dose-related manner. Similar to the results from in vivo experiments, in vitro Sal A also increased the protein expression of phosphorylated-eukaryotic initiation factor 4E binding protein 1 (p-4EBP1) compared with vehicle. Furthermore, the cytoprotective activity of Sal A was inhibited by LY294002 and rapamycin. These findings indicate that Sal A can ameliorate renal I/R injury and promote tubular cell survival partly via the Akt/mTOR/4EBP1pathway. Sal A could be a candidate compound to prevent ischemic tissue damage.

Activation of the AMPK-SIRT1 pathway contributes to protective effects of Salvianolic acid A against lipotoxicity in hepatocytes and NAFLD in mice

“…Sal A also attenuated angiotensin Ⅱ-induced apoptosis in murine peritoneal macrophages (Li et al, 2016) and protected cardiomyocytes from toxicity induced by arsenic trioxide, via inhibition of the MAPK pathway (Zhang et al, 2017). Furthermore, Sal A improved ischemia-reperfusion-stimulated injury in brain, renal, and intestines (Hou et al, 2016;Song et al, 2018;Zu et al, 2018). In the liver, Sal A significantly reduced chronic alcohol feedingor carbon tetrachloride-induced liver injury in rats (Wu et al, 2007;Shi et al, 2018a).…”

Clemaichinenoside protects renal tubular epithelial cells from hypoxia/reoxygenation injury in vitro through activating the Nrf2/HO‐1 signalling pathway

“…First, we only evaluated the effect of AR on renal I/R injury in vitro. An in vivo animal study will be considered in subsequent studies . Second, how AR can be delivered to the injured kidney and how AR can induce Nfr2 translocation will be considered in the following studies.…”

Supramolecular Nanofibers Containing Arginine-Glycine-Aspartate (RGD) Peptides Boost Therapeutic Efficacy of Extracellular Vesicles in Kidney Repair

“…The cells were grown at 37 °C in a humidified 5% CO 2 atmosphere. To mimic IRI in vitro , HK-2 cells were incubated in a humidified hypoxic/ischemic chamber at 37 °C for 6 h (5% CO 2 , 1% O 2 , and 94% N 2 atmosphere), as previously reported. , Subsequently, HK-2 cells were incubated in a reoxygenated environment with 95% air and 5% CO 2 for an additional 24 h, during which time cells were incubated with RGD hydrogels loaded with EVs without let-7a-5p (EV-inhibitor let‑7a‑5p ) or EV-inhibitor NC .…”