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Scutellarin exertsprotective effectsagainstatherosclerosis inrats by regulatingthe Hippo–FOXO3A andPI3K/AKT signalingpathways Yufeng FuShuangyong SunHuijun Sun2019 год

Scutellarin exerts protective effects against atherosclerosis in rats by regulating the Hippo–FOXO3A and PI3K/AKT signaling pathways
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Страница публикацииПубликация в OpenAlex
Аннотация: Abstract Atherosclerosis (AS), a progressive disorder, is one of the tough challenges in the clinic. Scutellarin, an extract from Herba Erigerontis, is found to have oxygen‐free radicals scavenging effects and antioxidant effects. In this study, we aimed to investigate the anti‐AS effects of scutellarin is related to controlling the Hippo–FOXO3A and PI3K/AKT signal pathway. To establish an AS model, the rats in the scutellarin and model groups were intraperitoneally injected with vitamin D 3 and then fed a high‐fat diet for 12 weeks. In addition, in vitro angiotensin II‐induced apoptosis of human aortic endothelial cells (HAECs) were used to establish models. Scutellarin significantly reduced blood lipid levels and increased antioxidase levels in both models. Additionally, scutellarin inhibited reactive oxygen species generation and apoptosis in HAECs. The impaired vascular barrier function was restored by using scutellarin in AS rats and in HAECs cells characterized by inhibiting mammalian sterile‐20‐like kinases 1 (Mst1) phosphorylation, Yes‐associated protein (YAP) phosphorylation, forkhead box O3A (FOXO3A) phosphorylation at serine 207, nuclear translocation of FOXO3A, and upregulating protein expression of AKT and FOXO3A phosphorylation at serine 253. Scutellarin significantly reduced Bcl‐2 interacting mediator of cell death (Bim), caspase‐3, APO‐1, CD95 (Fas), and Bax: Bcl‐2‐associated X (Bax) levels and activated Bcl‐2: B‐cell lymphoma‐2 (Bcl‐2). Scutellarin also significantly inhibited the expression of Mst1, YAP, FOXO3A at the messenger RNA level. When Mst1 was overexpressed or phosphoinositide 3‐kinases suppressed, the effects of scutellarin were significantly blocked. In conclusion, the results of the present study suggest that scutellarin exerts protective effects against AS by inhibiting endothelial cell injury and apoptosis by regulating the Hippo–FOXO3A and PI3K/AKT signal pathways.
Год издания: 2019
Авторы: Yufeng Fu, Shuangyong Sun, Huijun Sun, Jinyong Peng, Xiaodong Ma, Liuchi Bao, Renpeng Ji, Chunxu Luo, Cong Gao, Xiaoxue Zhang, Yue Jin
Издательство: Wiley
Источник: Journal of Cellular Physiology
Ключевые слова: Hippo pathway signaling and YAP/TAZ, FOXO transcription factor regulation, Axon Guidance and Neuronal Signaling
Другие ссылки: Journal of Cellular Physiology (HTML)
PubMed (HTML)