Choi Eun Sik, Yoon Jung Joo, Han Byung Hyuk, Jeong Da Hye, Kim Hye Yoom, Ahn You Mee, Eun So Young, Lee Yun Jung, Kang Dae Gill, Lee Ho Sub
College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, 460 Iksan-daero, Iksan-si, Jeollabuk-do 54538, Republic of Korea.
Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460 Iksan-daero, Iksan-si, Jeollabuk-do 54538, Republic of Korea.
Evid Based Complement Alternat Med. 2018 Jun 25;2018:1024974. doi: 10.1155/2018/1024974. eCollection 2018.
Samul-Tang (SMT), consisting of four medicinal herbs, is a well-known herbal prescription treating hematological disorders related symptoms. Our previous study demonstrated that SMT attenuated inflammation of vascular endothelial cells. In condition of retained vascular dysfunction, vascular inflammation is initiated and results in activation of smooth muscle cells (SMCs). Activated SMCs lose control of cell cycle regulation and migrate into intima, resulting in formation of atheroma. Here, we further investigated whether SMT suppresses proliferation and migration of SMCs. SMT showed antiproliferative effects on SMCs by suppressing [H]-thymidine incorporation against TNF- stimulation. Underlying mechanisms of antiproliferative effects were found to be resulting from cell cycle regulation. SMT downregulated expression of cyclin D1-CDK4 and cyclin E-CDK2 complexes and upregulated p21 and p27. SMT also suppressed migration of SMCs against TNF- stimulation. This is thought to have resulted from suppressing MMP2 and MMP9 expressions and ROS production. In summary, SMT attenuates abnormal migration of vascular smooth muscle cells via regulating cell cycle and suppressing MMPs expression and ROS production. Our study suggests that SMT, a traditionally used herbal formula, protects vascular smooth muscle cells and might be used as an antiatherosclerotic drug.
四君子汤（SMT）由四味草药组成，是一种治疗血液系统疾病相关症状的著名中药方剂。我们之前的研究表明，SMT可减轻血管内皮细胞炎症。在血管功能障碍持续存在的情况下，血管炎症被引发并导致平滑肌细胞（SMC）活化。活化的SMC失去对细胞周期调控的控制并迁移至内膜，导致动脉粥样硬化斑块形成。在此，我们进一步研究了SMT是否能抑制SMC的增殖和迁移。SMT通过抑制[H]-胸腺嘧啶核苷掺入对肿瘤坏死因子（TNF）刺激的反应，对SMC显示出抗增殖作用。发现抗增殖作用的潜在机制是由细胞周期调控引起的。SMT下调细胞周期蛋白D1-细胞周期蛋白依赖性激酶4（cyclin D1-CDK4）和细胞周期蛋白E-细胞周期蛋白依赖性激酶2（cyclin E-CDK2）复合物的表达，并上调p21和p27的表达。SMT还抑制了SMC对TNF刺激的迁移。这被认为是由于抑制基质金属蛋白酶2（MMP2）和基质金属蛋白酶9（MMP9）的表达以及活性氧（ROS）的产生所致。总之，SMT通过调节细胞周期并抑制基质金属蛋白酶的表达和ROS产生，减轻血管平滑肌细胞的异常迁移。我们的研究表明，传统使用的中药方剂SMT可保护血管平滑肌细胞，可能用作抗动脉粥样硬化药物。
