Zhao Jianjun, Shu Zhiyun, Li Xiangjun, Zhang Wenqing, Sun Mengze, Song Wenxiao, Cheng Hongyuan, Shi Shaomin
Department of Respiratory Medicine, China-Japan Union Hospital of Jilin University, Changchun, 130000, China.
Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, Changchun, 130000, China.
Lipids Health Dis. 2025 May 24;24(1):187. doi: 10.1186/s12944-025-02611-9.
Dehydrodiisoeugenol (Deh) has demonstrated positive effects in the prevention and treatment of cardiovascular disease (CVD) caused by lipid overload, but its specific mechanism of action remains poorly understood. The aim of this study was to investigate the possible mechanisms by which Deh modulates the mitochondrial dysfunction induced by palmitate (PA) in vascular smooth muscle cells (VSMCs).
A PA-induced high-fat model of VSMCs was established, and the effect of PA on the VSMCs on function was detected by evaluating the oxidative stress and apoptosis of cells, as well as mitochondrial function. The expression of dynamin-related protein 1 (Drp1) was detected by immunofluorescence and immunoprecipitation. The key targets of Deh for the treatment of mitochondria-related diseases were screened by bioinformatics analysis and molecular docking techniques. Finally, the role of Silent information regulator 1 (SIRT1) in the treatment of PA-induced mitochondrial dysfunction in VSMCs by Deh was explored by administrating Deh as well as SIRT1 activator (CAY10602, CAY) and SIRT1 inhibitor (JGB1741, JGB).
The results showed that PA concentration-dependently increased oxidative stress and apoptosis in VSMCs, while modulating the acetylation of Drp1, promoting its expression and mitochondrial ectopia, thereby inducing mitochondrial dysfunction. Bioinformatics analysis and molecular docking indicated that SIRT1 may be a key target of Deh for the treatment of mitochondria-related diseases. Follow-up experiments revealed that Deh significantly inhibited PA-induced mitochondrial dysfunction in VSMCs by suppressing acetylation and expression of Drp1 and reducing mitochondrial ectasia, an effect that was achieved by regulating SIRT1.
Deh was able to inhibit Drp1 expression and mitochondrial ectopia by reducing Drp1 acetylation through activation of SIRT1, thereby inhibiting PA-induced mitochondrial dysfunction effects in VSMCs, ameliorating pathological processes, such as cellular oxidative stress and apoptosis, and maintaining stable cellular functions.
脱氢二异丁香酚（Deh）已在脂质过载所致心血管疾病（CVD）的防治中显示出积极作用，但其具体作用机制仍不清楚。本研究旨在探讨Deh调节棕榈酸（PA）诱导的血管平滑肌细胞（VSMC）线粒体功能障碍的可能机制。
建立PA诱导的VSMC高脂模型，通过评估细胞的氧化应激、凋亡以及线粒体功能来检测PA对VSMC功能的影响。通过免疫荧光和免疫沉淀检测发动蛋白相关蛋白1（Drp1）的表达。采用生物信息学分析和分子对接技术筛选Deh治疗线粒体相关疾病的关键靶点。最后，通过给予Deh以及SIRT1激活剂（CAY10602，CAY）和SIRT1抑制剂（JGB1741，JGB），探讨沉默信息调节因子1（SIRT1）在Deh治疗PA诱导的VSMC线粒体功能障碍中的作用。
结果显示，PA浓度依赖性地增加VSMC中的氧化应激和凋亡，同时调节Drp1的乙酰化，促进其表达和线粒体异位，从而诱导线粒体功能障碍。生物信息学分析和分子对接表明，SIRT1可能是Deh治疗线粒体相关疾病的关键靶点。后续实验表明，Deh通过抑制Drp1的乙酰化和表达以及减少线粒体扩张，显著抑制PA诱导的VSMC线粒体功能障碍，这一作用是通过调节SIRT1实现的。
Deh能够通过激活SIRT1减少Drp1乙酰化，从而抑制Drp1表达和线粒体异位，进而抑制PA诱导的VSMC线粒体功能障碍效应，改善细胞氧化应激和凋亡等病理过程，维持细胞功能稳定。
