SIRT1/AMPK and Akt/eNOS signaling pathways are involved in endothelial protection of total aralosides of Aralia elata (Miq) Seem against high‐fat diet‐induced atherosclerosis in ApoE−/− mice

Abstract

Total aralosides of Aralia elata (Miq) Seem (TASAESs) possess multiple pharmacological activity, such as anti‐inflammation, antioxidation, and antiapoptosis. However, there is no literature reporting the antiatherosclerotic effect and mechanism of TASAES so far. The aim of this study was to investigate the antiatherosclerotic effects in high‐fat diet‐induced ApoE−/− mice and potential mechanism of TASAES in ox‐LDL‐injured endothelial cells. In vivo assay, our data demonstrated that TASAES significantly reduced the atherosclerotic plaque size and caspase‐3 expression level in aortic valve. In vitro, we found that TASAES could increase endothelial cell viability, attenuated mitochondrial membrane potential depolarization, and endothelial cells apoptosis. In addition, we found that TASAES could activate SIRT1/AMPK and Akt/eNOS signaling pathways. Importantly, EX527, SIRT1 siRNA, and LY294002, Akt siRNA, remarkably abolished the antiapoptotic effects of TASAES. In conclusion, this study demonstrated that SIRT1/AMPK and Akt/eNOS signaling pathways are involved in endothelial protection of TASAES against atherosclerotic mice, suggesting that TASAES is a candidate drug for atherosclerosis treatment.

Araloside C attenuates atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy

“…Recently, many natural products have been studied to determine their impact on atherosclerosis [18]. Our group and several others have reported that TASAES exerts therapeutic effects on myocardial damage [34,35] and atherosclerosis [22,23]. AsC, isolated from TASAES, was also reported to have powerful cardioprotective effects against ischemia-reperfusion injury in our previous study [20,21].…”

“…After rinsing, the sections were incubated for 1 h with the secondary antibody at room temperature and then incubated with 0.5 g/L DAPI containing antifluorescence quenching agent for 5 min. Images were obtained with a the Tissue FAXS microscope (Tissue FAX plus; Tissue Gnostics, Vienna, Austria) and analyzed based on our previous method [22].…”

“…Moreover, we found that total saponins of Aralia elata (Miq.) (TASAES) protected against endothelial cell injury and atherosclerosis in ApoE-/-mice [22,23]. According to the emerging reports of the cardioprotective effects of AsC and the endothelial protective effects of TASAES, we believe that the antiatherosclerotic effects of AsC and its possible molecular mechanism need to be elucidated.…”

The atheroprotective roles of heart-protecting musk pills against atherosclerosis development in apolipoprotein E-deficient mice

“…It is well-established that dyslipidemia is a crucial risk factor for atherosclerosis and regulation of blood lipid profiles has been given priority in the treatment of atherosclerotic CVDs (2,5). Moreover, therapeutic approaches protecting against vascular intimal impairment have been proved to inhibit atheroma lesion progression (6,7). Currently, several modern drugs such as statins have been used for the treatment of atherosclerosis.…”

SIRT1-Mediated Protective Effect of Aralia elata (Miq.) Seem against High-Glucose-Induced Senescence in Human Umbilical Vein Endothelial Cells

“…Previous studies showed that triterpenoid saponins from AS leaves exert antitumor effects [18], and the bark and roots of AS have been used as tonics and diuretics in the treatment of the common cold, gastric ulcer, diabetes, neurasthenia, hepatitis, and inflammatory diseases in Chinese folk medicine [19]. Furthermore, AS exhibits a series of pharmacological functions, including anti-inflammatory, antioxidant, hypolipidemic, and antidiabetic properties [20,21]. Despite the development and application of AS, few studies have focused on it in preventing EC senescence.…”