Protective Effects of Total Saponins of Aralia elata (Miq.) on Endothelial Cell Injury Induced by TNF-α via Modulation of the PI3K/Akt and NF-κB Signalling Pathways

Abstract

Atherosclerosis is an arterial disease associated with inflammation. Hence, the discovery of novel therapeutic agents for suppressing inflammatory responses is urgent and vital for the treatment of atherosclerosis in cardiovascular diseases. The total saponins of Aralia elata (Miq.) Seem. (TAS) are the main components extracted from the Chinese traditional herb Longya Aralia chinensis L., a folk medicine used in Asian countries for treating numerous diseases, enhancing energy and boosting immunity. However, the protective effects of TAS against inflammation-triggered vascular endothelial dysfunction, a critical early event during the course of atherosclerosis, and the potential mechanisms of this protection have been not demonstrated. Accordingly, the aim of this study was to investigate the anti-inflammatory and anti-apoptotic effects and the protective mechanisms of TAS, and show how TAS ameliorates human umbilical vein endothelial cell (HUVEC) damage caused by tumour necrosis factor-α (TNF-α). The results indicated that TAS exerted cytoprotective effects by inhibiting TNF-α-triggered HUVEC apoptosis, mitochondrial membrane potential depolarisation, and the regulation of inflammatory factors (IL-6, MCP-1, and VCAM-1) while suppressing NF-κB transcription. Furthermore, this phenomenon was related to activation of the phosphoinositide 3-kinase (PI3K)/Akt signalling pathway. Blocking the Akt pathway with LY294002, a PI3K inhibitor, reversed the cytoprotective effect of TAS against TNF-α-induced endothelial cell death. Moreover, LY294002 partially abolished the effects of TAS on the upregulation of the Bcl-2 family of proteins and the downregulation of Bax protein expression. In conclusion, the results of our study suggest that TAS suppresses the inflammation and apoptosis of HUVECs induced by TNF-α and that PI3K/Akt signalling plays a key role in promoting cell survival and anti-inflammatory reactions during this process.

Aspirin Enhances the Protection of Hsp90 from Heat-Stressed Injury in Cardiac Microvascular Endothelial Cells Through PI3K-Akt and PKM2 Pathways

“…The molecule related to cellular apoptosis, Cyt-C, was induced in the whole process of heat stress, which was in agreement with the results of apoptosis rate during heat stress. The complex of Hsp90 with Akt and PKM2 caused by physical interaction directly mediates the stability and activation of Akt and PKM2, which are indispensable for regulating their downstream survival proteins, such as HSF-1 and Bcl-2, which is critical for their biological functions in regulating glycolysis, mitochondria respiration and apoptosis [23][24][25][26][27]. In addition, Hsp70 can assist the process through integrating with these complexes [23].…”

Rice Protein Exerts Anti-Inflammatory Effect in Growing and Adult Rats via Suppressing NF-κB Pathway

“…Upon activation of NF-κB, the transcription of a number of inflammatory genes can be activated, e.g., tumor necrotic factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), monocyte chemoattractant protein-1 (MCP-1), etc. [1,[16][17][18][19]. This is the basic functional mechanism through which the NF-κB transcription factor induces an inflammatory response.…”

Effect of alcohol tincture of Aralia elata on the organism of rats and their gut microbiota against the background of excessive fat diet

“…Studies on laboratory mice with non-alcohol steatohepatitis caused by diet with high content of fat, confirmed the healing effect of arazolides from A. еlata, isolated from the plant's roots (Luo et al, 2015). Molecular mechanisms of anti-inflam-matory and anti-apoptotic action have been studied and general protective effect of saponins of A. еlata was proved in cases of damage to endothelial cells of blood vessels on the example of endothelium of the umbilical vein of a human, affected by necrosis factor-α (TNF-α) (Zhou et al, 2018).…”