Total saponins of Aralia elata(Miq)Seem protect tumor necrosis factor-α-induced human umbilical vein endothelial cells via PI3K/Akt and NF-κB signal pathways / 中国药理学与毒理学杂志

ABSTRACT

It is now thought that atherosclerosis,although due to enhanced lipid deposition,is mainly the result of a series inflammatory process.Total saponins of Aralia elata (Miq)Seem(TASAES)from the Chinese traditional herb Longya Araliachinensis L.,a folk medicine used for treating various diseases, increasing energy and improving the body′s ability to prevent hypoxia in Asian countries has attracted widespread attention. However, the ability of TASAES on inflammation-triggered vascular endothelial cell injury, a key early event in the pathogenesis of atherosclerosis, and its potential mechanisms of this protection have never been demonstrated. The present study determined the anti-inflammatory and anti-apoptoticactivities and protective mechanisms of the total aralosides of Araliaelata(Miq)Seem (TASAES) ameliorate tumor necrosis factor-α (TNF-α)-induced human umbilical vein endothelial cells (HUVECs) injury. Our results indicate that TASAES pretreatment provided cytoprotective effects by suppressing TNF-α-induced HUVECs apoptosis, mitochondrial membrane depolarization, caspase-3 activation, and modulation of inflammatory factors (IL-6, MCP-1 and VCAM-1), meanwhile inhibiting NF- κB transcription. Furthermore, the effect was correlated with the activation of the PI3K/Akt signal pathway. Blocking Akt activation with the PI3K inhibitor LY294002 effectively reversed the protective effect of TASAES against TNF-α-induced cell apoptosis.Moreover,the PI3K inhibitor partially blocked the effects of TASAES on the increasing of Bcl-2 and Bcl-xl protein expression,and inactivation of Bax protein expression. In conclusion, the results showed that TASAES decreased the inflammation and apoptosis of HUVECs caused by TNF-α treatment,and PI3K played a crucial role in enhancing cell sur-vival during this process.