Reactive oxygen species (ROS) induced by high glucose and high fat of diabetes mellitus (DM) finally caused the occurrence and progression of atherosclerosis and other macrovascular complications. Paeonol (Pae) exhibits anti-inflammation, antioxidation, and antiatherosclerosis activities. However, the role of Pae in diabetic cardiopathy has not been fully understood. Therefore, we aimed to investigate the role of Pae in diabetic cardiovascular diseases. Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose and palmitic acid (HG/HP), a model DM environment and different doses of Pae. The viability and apoptotic rate of HUVECs were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assay, respectively. Oxidative indicators (ROS, malondiadehyde [MDA], superoxide dismutase [SOD]), and inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6) were detected by 2,7-dichlorodihydrofluorescein diacetate, colorimetry, and enzyme-linked immunosorbent assay. The protein levels of Sirtuin type 1 (SIRT1), Bcl-2, Bax, Cleaved caspase-3, p-p65, and p-65 were detected by Western blot. The mRNA levels of Bcl-2 and Bax were detected by quantitative real-time polymerase chain reaction. The acetylation and protein levels of forkhead box O3a (FOXO3a) were detected by immunoprecipitation assay. SIRT1 silencing was used to confirm the role of Pae in the resistance to apoptosis, oxidative stress, and inflammatory response. Pae increased SIRT1 expression, cell viability, and SOD activity and suppressed apoptosis, the levels of p-p65/p-65, ROS, MDA, and inflammatory cytokines, and the expression of acetylated-FOXO3a induced by HG/HP in HUVECs. SIRT1 silencing abrogated the effect of Pae on HG/HP-mediated HUVECs. Inhibitory effect of Pae on apoptosis, oxidative stress, and inflammatory response in HUVECs induced by HG/HP induced through regulating SIRT1/FOXO3a/NF-κB pathway.

中文翻译：

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丹皮酚对高糖和棕榈酸通过调节 SIRT1/FOXO3a/NF-κB 通路诱导的人脐静脉内皮细胞凋亡、氧化应激和炎症反应的抑制作用

糖尿病（DM）高糖高脂诱导的活性氧（ROS）最终导致动脉粥样硬化等大血管并发症的发生和发展。Paeonol (Pae) 具有抗炎、抗氧化和抗动脉粥样硬化活性。然而，Pae 在糖尿病性心脏病中的作用尚未完全了解。因此，我们旨在研究 Pae 在糖尿病心血管疾病中的作用。人脐静脉内皮细胞 (HUVEC) 暴露于高葡萄糖和棕榈酸 (HG/HP)、模型 DM 环境和不同剂量的 Pae。分别通过 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide 和流式细胞术测定 HUVECs 的活力和凋亡率。氧化指示剂（ROS、丙二醛 [MDA]、超氧化物歧化酶 [SOD]）、采用2,7-二氯二氢荧光素二乙酸酯、比色法和酶联免疫吸附法检测炎性细胞因子（肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6）。通过蛋白质印迹检测 Sirtuin 1 型 (SIRT1)、Bcl-2、Bax、Cleaved caspase-3、p-p65 和 p-65 的蛋白质水平。的 mRNA 水平通过定量实时聚合酶链式反应检测Bcl-2和Bax。通过免疫沉淀法检测叉头盒O3a（FOXO3a）的乙酰化和蛋白质水平。SIRT1沉默用于确认 Pae 在抗凋亡、氧化应激和炎症反应中的作用。Pae 增加 SIRT1 表达、细胞活力和 SOD 活性并抑制细胞凋亡、p-p65/p-65、ROS、MDA 和炎性细胞因子的水平，以及 HG/HP 诱导的 HUVECs 中乙酰化 FOXO3a 的表达。SIRT1沉默消除了 Pae 对 HG/HP 介导的 HUVECs 的影响。Pae 通过调节 SIRT1/FOXO3a/NF-κB 通路对 HG/HP 诱导的 HUVECs 凋亡、氧化应激和炎症反应的抑制作用。