Scutellarin exerts protective effects against atherosclerosis in rats by regulating the Hippo–FOXO3A and PI3K/AKT signaling pathways

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.

Angiotensin type 1 receptor regulates yes‑associated protein in vascular endothelial cells

“…VECs. Recent studies have revealed that Ang II increases EC YAP phosphorylation (23), and that angiotensin-converting enzyme 2 activation attenuates pulmonary vascular remodeling via the induction of pulmonary arterial cell apoptosis by upregulating YAP phosphorylation (24). The present results were consistent with these recent studies because they indicated that Ang II increased YAP phosphorylation and regulated VEC activity.…”

<p>Metformin Activates the AMPK-mTOR Pathway by Modulating lncRNA <em>TUG1</em> to Induce Autophagy and Inhibit Atherosclerosis</p>

“…Rats in the control group were fed a normal diet, whereas all other rats were fed a high-fat diet and vitamin D 3 to induce AS (the composition of the rat diet is listed in Table S1) and was in accordance with the literature. 23,24,25 Food was provided adlibitum. After allowing the rats to acclimatize for in the corresponding group.…”

MicroRNA sequences modulating inflammation and lipid accumulation in macrophage “foam” cells: Implications for atherosclerosis

“…Notably, the atheroprotective effect of steady laminar flow in major arteries is linked with inhibition of Hippo/YAP effector function[ 228 ] while activation of this pathway is linked with vascular remodelling, and switching of arterial smooth muscle cells to the “synthetic” proliferative phenotype in response to biochemical stretch[ 229 ]. The effector function of YAP is linked with accelerated atherosclerosis in apoE -/- mice[ 230 ], while the herbal extract Scutellarin can protect against atherosclerosis in rats by modulating the Hippo-YAP-Forkhead box (FOXO)3A transduction pathway[ 231 ].…”