Shi Mengqing, Ning Zhongping
Graduate School, Shanghai University of Traditional Chinese Medicine (SHUTCM), Shanghai, 201203, China.
Shanghai University of Traditional Chinese Medicine (SHUTCM), Shanghai, 201203, China.
Sci Rep. 2025 Feb 20;15(1):6200. doi: 10.1038/s41598-025-89895-0.
Schisandrin B (Sch B) derived from Schisandra chinensis, is known for its anti-inflammatory and anti-microbial properties. The study aimed to explore Sch B's protective roles and underlying mechanisms in angiotensin II (Ang II) - induced ferroptosis, atrial fibrosis, and AF using both in vivo and in vitro models. AF mice model generated induced by Ang II and established an in vitro model using the HL-1 cell line induced by Ang II. We assessed atrial fibrosis through histological analysis and oxidative stress analysis. We employed RT-qPCR and Western blot techniques to evaluate mRNA and protein expression. Sch B significantly attenuated Ang II-induced AF development, atrial apoptosis, and myocardial injury-related molecules, including CK-MB and LDH. Relative DHE intensity, MDA, NOX2, and NOX4 increased significantly, and SOD and CAT levels decreased markedly in Ang II-induced mice. Sch B treatment could inhibit atrial ROS production and oxidative stress in Ang II-infused mice. In addition, Sch B showed cardioprotective effects in Ang II-infused HL-1 cells. Sch B significantly reduced pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6, restored by EX527 (SIRT1 inhibitor). Sch B inhibited intracellular ROS generation and oxidative stress in HL-1 cells, which were restored by Ex-527. Furthermore, Sch B decreased the increase in Fe2 + concentration caused by Ang II infusion, which was recovered by Ex-527. Sch B markedly increased the expression of SIRT1, SLC7A11, GPX4 and FTH1 while reducing the expression patterns by Ex-527 treatment. Our experimental data suggest that Sch B protects against Ang II-induced ferroptosis, atrial fibrosis, and AF by activating SIRT1 in vivo and in vitro.
五味子乙素（Sch B）来源于五味子，以其抗炎和抗菌特性而闻名。本研究旨在利用体内和体外模型，探讨Sch B在血管紧张素II（Ang II）诱导的铁死亡、心房纤维化和房颤中的保护作用及潜在机制。通过Ang II诱导建立房颤小鼠模型，并使用Ang II诱导的HL-1细胞系建立体外模型。我们通过组织学分析和氧化应激分析评估心房纤维化。采用RT-qPCR和蛋白质免疫印迹技术评估mRNA和蛋白质表达。Sch B显著减轻了Ang II诱导的房颤发展、心房凋亡以及心肌损伤相关分子，包括肌酸激酶同工酶（CK-MB）和乳酸脱氢酶（LDH）。在Ang II诱导的小鼠中，相对二氢乙啶（DHE）强度、丙二醛（MDA）、NADPH氧化酶2（NOX2）和NADPH氧化酶4（NOX4）显著增加，超氧化物歧化酶（SOD）和过氧化氢酶（CAT）水平显著降低。Sch B治疗可抑制Ang II灌注小鼠的心房活性氧（ROS）产生和氧化应激。此外，Sch B在Ang II灌注的HL-1细胞中显示出心脏保护作用。Sch B显著降低了促炎细胞因子，包括白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6），而EX527（SIRT1抑制剂）可使其恢复。Sch B抑制HL-1细胞内ROS生成和氧化应激，而Ex-527可使其恢复。此外，Sch B降低了Ang II灌注引起的Fe2+浓度升高，而Ex-527可使其恢复。Sch B显著增加了SIRT1、溶质载体家族7成员11（SLC7A11）、谷胱甘肽过氧化物酶4（GPX4）和铁蛋白重链1（FTH1）的表达，而Ex-527处理则降低了其表达模式。我们的实验数据表明，Sch B在体内和体外通过激活SIRT1来保护机体免受Ang II诱导的铁死亡、心房纤维化和房颤。
