Aescin Protects Neuron from Ischemia-Reperfusion Injury via Regulating the PRAS40/mTOR Signaling Pathway

Abstract

Ischemic stroke is one of the major causes of disability; widely use of endovascular thrombectomy or intravenous thrombolysis leads to more attention on ischemia-reperfusion injury (I/R injury). Aescin, a natural compound isolated from the seed of the horse chestnut, has been demonstrated anti-inflammatory and antiedematous effects previously. This study was aimed at determining whether aescin could induce protective effects against ischemia-reperfusion injury and exploring the underlying mechanisms in vitro. Primary cultured neurons were subjected to 2 hours of oxygen-glucose deprivation (OGD) followed by 24 hours of simulated reperfusion. Aescin, which worked in a dose-dependent manner, could significantly attenuate neuronal death and reduce lactate dehydrogenase (LDH) release after OGD and simulated reperfusion. Aescin treatment at a concentration of 50 μg/ml provided protection with fewer side effects. Results showed that aescin upregulated the phosphorylation level of PRAS40 and proteins in the mTOR signaling pathway, including S6K and 4E-BP1. However, PRAS40 knockdown or rapamycin treatment was able to undermine and even abolish the protective effects of aescin; meanwhile, the levels of phosphorylation PRAS40 and proteins in the mTOR signaling pathway were obviously decreased. Hence, our study demonstrated that aescin provided neuronal protective effects against I/R injury through the PRAS40/mTOR signaling pathway in vitro. These results might contribute to the potential clinical application of aescin and provide a therapeutic target on subsequent cerebral I/R injury.

mTOR: A Potential New Target in Nonalcoholic Fatty Liver Disease

“…PRAS40 [ 19 ] and Raptor [ 20 ] can act together as endogenous inhibitors of mTORC1. PRAS40 is a target for insulin regulation by mTORC1 activity inhibitors [ 21 ]. The FRB domain is the main target of 13 kDa FK506- and rapamycin-binding protein (FKBP2) and is inhibited by this protein, which explains why mTORC1 is sensitive to rapamycin [ 22 ].…”

Escin suppresses immune cell infiltration and selectively modulates Nrf2/HO-1, TNF-α/JNK, and IL-22/STAT3 signaling pathways in concanavalin A-induced autoimmune hepatitis in mice

“…Currently, escin is therapeutically indicated for chronic venous insufficiency, varicose veins, hemorrhoids, hematoma, venous congestion, diabetic retinopathy, and postoperative edema. On the other hand, recent studies has shown its promising efficacy in multiple models of inflammation including a high fat diet (Avci et al 2010 ), mouse paw edema (Matsuda et al 1997 ), neuronal ischemia reperfusion injury (Gao et al 2020 ), and rat pleuritis models (Yang et al 2020 ). Yet, it is not fully investigated whether escin may have a protective effect on Con A-induced AIH or not, and if so, its underlying mechanisms.…”