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SIRT1/AMPK and Akt/eNOS signaling pathways are involved in endothelial protection of total aralosides of Aralia elata ( Miq ) S eem against high‐fat diet‐induced atherosclerosis in ApoE −/− mice
Author(s) -
Luo Yun,
Lu Shan,
Ai Qidi,
Zhou Ping,
Qin Meng,
Sun Guibo,
Sun Xiaobo
Publication year - 2019
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6269
Subject(s) - ampk , enos , protein kinase b , pterostilbene , signal transduction , pi3k/akt/mtor pathway , apoptosis , chemistry , microbiology and biotechnology , ly294002 , pharmacology , phosphorylation , resveratrol , biology , biochemistry , protein kinase a , nitric oxide synthase , enzyme
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.