Geng Jianan, Fu Wenwen, Yu Xiaofeng, Lu Zeyuan, Liu Yanzhe, Sun Mingyang, Yu Ping, Li Xin, Fu Li, Xu Huali, Sui Dayun
Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, China.
Institute of Traditional Chinese Medicine Innovation, Jilin Yatai Pharmaceutical Co., Ltd., Changchun, China.
Front Pharmacol. 2020 Apr 22;11:500. doi: 10.3389/fphar.2020.00500. eCollection 2020.
The initiation of atherosclerosis (AS) induced by dyslipidemia is accompanied by endothelial dysfunction, including decreased healing ability and increased recruitment of monocytes. Studies showed ginsenoside Rg3 has potential to treat diseases associated with endothelial dysfunction which can protects against antineoplastic drugs induced cardiotoxicity by repairing endothelial function, while the effect and mechanism of Rg3 on dyslipidemia induced endothelial dysfunction and AS are not clear. Therefore, we investigated the effects of Rg3 on oxidized low-density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVECs) dysfunction and high-fat diets (HFD) induced atherosclerosis in ApoE mice, as well as the mechanism. For assay, Rg3 enhanced healing of HUVECs and inhibited human monocytes (THP-1) adhesion to HUVECs disturbed by ox-LDL, down-regulated focal adhesion kinase (FAK)-mediated expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1); restrained the FAK-mediated non-adherent dependent pathway containing matrix metalloproteinase (MMP)-2/9 expression, activation of nuclear factor-kappa B (NF-κB), high mRNA levels of monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6), besides Rg3 up-regulated peroxisome proliferators-activated receptor γ (PPARγ) in ox-LDL-stimulated HUVECs. GW9662, the PPARγ-specific inhibitor, can repressed the effects of Rg3 on ox-LDL-stimulated HUVECs. For assay, Rg3 significantly reduced atherosclerotic pathological changes in ApoE mice fed with HFD, up-regulated PPARγ, and inhibited activation FAK in aorta, thus inhibited expression of VCAM-1, ICAM-1 in intima. We conclude that Rg3 may protect endothelial cells and inhibit atherosclerosis by up-regulating PPARγ repressing FAK-mediated pathways, indicating that Rg3 have good potential in preventing dyslipidemia induced atherosclerosis.
血脂异常引发的动脉粥样硬化（AS）起始阶段伴有内皮功能障碍，包括愈合能力下降和单核细胞募集增加。研究表明，人参皂苷Rg3具有治疗与内皮功能障碍相关疾病的潜力，其可通过修复内皮功能来预防抗肿瘤药物诱导的心脏毒性，而Rg3对血脂异常诱导的内皮功能障碍和AS的作用及机制尚不清楚。因此，我们研究了Rg3对氧化型低密度脂蛋白（ox-LDL）诱导的人脐静脉内皮细胞（HUVECs）功能障碍以及高脂饮食（HFD）诱导的ApoE小鼠动脉粥样硬化的影响及其机制。在实验中，Rg3促进了HUVECs的愈合，并抑制了ox-LDL干扰的人单核细胞（THP-1）与HUVECs的黏附，下调了黏着斑激酶（FAK）介导的血管细胞黏附分子1（VCAM-1）和细胞间黏附分子1（ICAM-1）的表达；抑制了FAK介导的包含基质金属蛋白酶（MMP）-2/9表达、核因子-κB（NF-κB）激活、单核细胞趋化蛋白1（MCP-1）和白细胞介素6（IL-6）高mRNA水平的非黏附依赖性途径，此外，Rg3上调了ox-LDL刺激的HUVECs中的过氧化物酶体增殖物激活受体γ（PPARγ）。PPARγ特异性抑制剂GW9662可抑制Rg3对ox-LDL刺激的HUVECs的作用。在实验中，Rg3显著减轻了高脂饮食喂养的ApoE小鼠的动脉粥样硬化病理变化，上调了PPARγ，并抑制了主动脉中FAK的激活，从而抑制了内膜中VCAM-1、ICAM-1的表达。我们得出结论，Rg3可能通过上调PPARγ并抑制FAK介导的途径来保护内皮细胞并抑制动脉粥样硬化，这表明Rg3在预防血脂异常诱导的动脉粥样硬化方面具有良好的潜力。
