Scutellarin exerts protective effects against atherosclerosis in rats by regulating the Hippo–FOXO3A and PI3K/AKT signaling pathways. Issue 10 (19th March 2019)

• Record Type: Journal Article
• Authors: Fu, Yufeng; Sun, Shuangyong; Sun, Huijun; Peng, Jinyong; Ma, Xiaodong; Bao, Liuchi; Ji, Renpeng; Luo, Chunxu; Gao, Cong; Zhang, Xiaoxue; Jin, Yue
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 10(2019:Oct.)
• Page Start: 18131
• Page End: 18145
• Publication Date: 2019-03-19
• Subjects: antioxidation -- apoptosis -- atherosclerosis -- Hippo–FOXO3A -- PI3K/AKT -- scutellarin; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28446
• Languages: English
• ISSNs: 0021-9541

Abstract

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. Abstract : Accumulating evidence shows that endothelial cell injury‐induced apoptosis plays a key role in the development and pathogenesis of atherosclerosis. Reactive oxygen species (ROS) triggers the activation of multiple signaling pathways and promotes apoptosis of cells. Our present study suggests that scutellarin exerts protective effects against atherosclerosis by inhibiting the formation of ROS and endothelial cell injury and apoptosis via regulating Hippo–FOXO3a and PI3K/AKT signal pathway.