Zhang Xiaogang, Shi Mengqing, Xing Zhongying, Su Jie, Gu Yuying, Ning Zhongping
Department of Cardiology, Shanghai Pudong New Area Zhoupu Hospital (Shanghai Health Medical College Affiliated Zhoupu Hospital) Shanghai.
201318, China.
Iran J Basic Med Sci. 2025;28(7):946-954. doi: 10.22038/ijbms.2025.83918.18160.
Schisandrin B (SchB), extracted from , has antimicrobial and anti-inflammatory effects. The study aimed to investigate SchB's possible defense against angiotensin II (Ang II)-infused cardiac fibrosis and its molecular processes.
An equivalent volume of saline or Ang II (2.0 mg/kg/day, HY-13948, MedChemExpress) was administered subcutaneously to male C57BL/6 mice aged between 8 and 10 weeks. SchB (30 mg/kg/day, HY-N0089, MedChemExpress) was given via intraperitoneal injection two hours before Ang II infusion for 28 days. Comprehensive morphological, histological, and biochemical analyses were conducted. We evaluated the mRNA and protein expression levels using western blot and RT-qPCR techniques.
SchB treatment improves heart disease in Ang II-induced mice. SchB markedly lowered serum levels of cardiac fibrosis-related markers, including cTnI, cTnT, ANP, and BNP. In addition, SchB elevated sirtuin 1 (SIRT1) expression while reducing α-SMA, TGF-β1, collagen I, collagen III, and CTGF . Furthermore, SchB inhibited the migration of Ang II-infused rat cardiac fibroblasts. SchB increased SIRT1 expression while decreasing TGF-β1, α-SMA, collagen I, and collagen III, whereas EX-527, an inhibitor of SIRT1, recovered their activities . Furthermore, SchB elevated SIRT1 expression while lowering the expressions of p-PI3K (p85, Tyr458) and p-Akt (Ser473) proteins.
Our results suggest that SchB regulates the SIRT1/PI3K/Akt pathway to prevent Ang II-infused cardiac fibrosis.
从五味子中提取的五味子乙素（SchB）具有抗菌和抗炎作用。本研究旨在探讨SchB对血管紧张素II（Ang II）诱导的心脏纤维化的可能防御作用及其分子机制。
将等量的生理盐水或Ang II（2.0 mg/kg/天，HY-13948，MedChemExpress）皮下注射给8至10周龄的雄性C57BL/6小鼠。在Ang II输注前两小时通过腹腔注射给予SchB（30 mg/kg/天，HY-N0089，MedChemExpress），持续28天。进行了全面的形态学、组织学和生化分析。我们使用蛋白质印迹和逆转录定量聚合酶链反应技术评估mRNA和蛋白质表达水平。
SchB治疗改善了Ang II诱导的小鼠心脏病。SchB显著降低了血清中心脏纤维化相关标志物的水平，包括肌钙蛋白I（cTnI）、肌钙蛋白T（cTnT）、心钠素（ANP）和脑钠肽（BNP）。此外，SchB提高了沉默调节蛋白1（SIRT1）的表达，同时降低了α-平滑肌肌动蛋白（α-SMA）、转化生长因子-β1（TGF-β1）、I型胶原蛋白、III型胶原蛋白和结缔组织生长因子（CTGF）。此外，SchB抑制了Ang II处理的大鼠心脏成纤维细胞的迁移。SchB增加了SIRT1的表达，同时降低了TGF-β1、α-SMA、I型胶原蛋白和III型胶原蛋白的表达，而SIRT1抑制剂EX-527恢复了它们的活性。此外，SchB提高了SIRT1的表达，同时降低了磷酸化磷脂酰肌醇-3激酶（p-PI3K，p85，Tyr458）和磷酸化蛋白激酶B（p-Akt，Ser473）蛋白的表达。
我们的结果表明，SchB通过调节SIRT1/PI3K/Akt信号通路来预防Ang II诱导的心脏纤维化。
