异常增殖,迁移,血管平滑肌细胞(VSMCs)的泡沫细胞形成在动脉粥样硬化(AS)的发展中起作用。五味子素(Sch)是木酚素活性成分,具有广谱的药理作用。然而,Sch在AS过程中的作用尚不清楚。因此,本研究旨在探讨Sch对VSMCs的治疗作用及潜在机制。选择Ox-LDL为VSMC和巨噬细胞创造动脉粥样硬化损伤环境。MTT法,油红O染色,伤口愈合,用transwell实验和ELISA方法研究了Sch的表型效应。网络药理学,分子对接,流式细胞术,采用免疫印迹法研究Sch对AS进展的作用机制。我们的发现暗示Sch处理抑制了VSMC的增殖和迁移,并抑制了VSMC和巨噬细胞的ROS产生和炎性细胞因子的上调。此外,Sch通过下调LOX-1减少脂质摄取和泡沫细胞形成。机械上,我们发现Sch可以通过靶向JAK2抑制JAK2/STAT3信号的激活,并将细胞周期阻滞在GO/G1期。总之,Sch可以通过阻滞细胞周期和靶向JAK2调节JAK2/STAT3通路来抑制VSMCs的增殖和迁移。Sch可能是AS患者的潜在药物。
Abnormal proliferation, migration, and foam cell formation of Vascular smooth muscle cells (VSMCs) each play a role in the development of atherosclerosis (AS). Schisandrin (Sch) is the active lignan ingredient with broad-spectrum pharmacological effects. However, the role of Sch in the AS process is not clear. Therefore, this study was proposed to explore the therapeutic effect and potential mechanism of Sch on VSMCs. Ox-LDL was selected to create an atherosclerosis injury environment for VSMCs and macrophages. The MTT assay, Oil red O staining, wound healing, transwell experiments and ELISA were used to investigate the phenotype effects of Sch. Network pharmacology, molecular docking, flow cytometry, and western blot were used to investigate the underlying mechanisms of Sch on AS progression. Our findings implied that Sch treatment inhibited the proliferation and migration of VSMCs, and suppressed the ROS production and inflammatory cytokines up-regulation of VSMCs and macrophages. Moreover, Sch reduced lipid uptake and foam cell formation through downregulating LOX-1. Mechanistically, we found that Sch can inhibit the activation of JAK2/STAT3 signaling by targeting JAK2, and arrest cell cycle in GO/G1 phase. In summary, Sch can inhibit VSMCs proliferation and migration by arresting cell cycle and targeting JAK2 to regulating the JAK2/STAT3 pathway. Sch may serve as a potential drug for patients with AS.