Discipline of Chinese and Western Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
PLoS One. 2013 Aug 27;8(8):e74826. doi: 10.1371/journal.pone.0074826. eCollection 2013.
Vascular smooth muscle cell (VSMC) proliferation and migration triggered by inflammatory stimuli contributes importantly to the pathogenesis of atherosclerosis and restenosis. On the other hand, genipin, an aglycon of geniposide, exhibits diverse pharmacological functions such as antitumor and anti-inflammatory effects. The protective effects of genipin on the cardiovascular system have also been reported. However, the molecular mechanism involved remains unknown. This study aimed to elucidate the precise function of genipin in VSMCs, focusing particularly on the role of heme oxygenase-1 (HO-1), a potent anti-inflammatory enzyme. We found that pretreatment of genipin induced HO-1 mRNA and protein levels, as well as its activity in VSMCs. Genipin inhibited TNF-α-induced VSMC proliferation and migration in a dose-dependent manner. At the molecular level, genipin prevented ERK/MAPK and Akt phosphorylation while left p38 MAPK and JNK unchanged. Genipin also blocked the increase of ROS generation induced by TNF-α. More importantly, the specific HO-1 siRNA partially abolished the beneficial effects of genipin on VSMCs. These results suggest that genipin may serve as a novel drug in the treatment of these pathologies by inducing HO-1 expression/activity and subsequently decreasing VSMC proliferation and migration.
血管平滑肌细胞(VSMC)的增殖和迁移是动脉粥样硬化和再狭窄发病机制的重要因素，炎症刺激可触发这一过程。另一方面，京尼平是京尼平苷的苷元，具有多种药理作用，如抗肿瘤和抗炎作用。京尼平对心血管系统的保护作用也有报道。然而，其涉及的分子机制尚不清楚。本研究旨在阐明京尼平在 VSMCs 中的精确功能，特别关注血红素加氧酶-1(HO-1)的作用，HO-1 是一种有效的抗炎酶。我们发现，京尼平预处理诱导 VSMCs 中 HO-1 mRNA 和蛋白水平及其活性增加。京尼平呈剂量依赖性抑制 TNF-α诱导的 VSMC 增殖和迁移。在分子水平上，京尼平阻止了 ERK/MAPK 和 Akt 的磷酸化，而 p38 MAPK 和 JNK 则保持不变。京尼平还阻断了 TNF-α诱导的 ROS 生成增加。更重要的是，特异性 HO-1 siRNA 部分消除了京尼平对 VSMCs 的有益作用。这些结果表明，京尼平通过诱导 HO-1 的表达/活性，进而减少 VSMC 的增殖和迁移，可能成为治疗这些疾病的一种新型药物。
