Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30322, USA.
Biochem Biophys Res Commun. 2012 Oct 19;427(2):349-54. doi: 10.1016/j.bbrc.2012.09.061. Epub 2012 Sep 17.
Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murine model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-κB) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase Cγ1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-κB-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.
胡椒碱（piplartine，PL）是长胡椒（Piper longum L.）中发现的一种生物碱，具有良好的抗血小板聚集、抗炎和抗癌特性；然而，PL 在预防动脉粥样硬化中的作用尚不清楚。我们在动脉粥样硬化加速的体内小鼠模型中评估了 PL 的抗动脉粥样硬化潜力，并在体外定义了其在主动脉血管平滑肌细胞（VSMCs）中的作用机制。局部给予 PL 可显著减少体内斑块形成以及增殖和核因子-κB（NF-κB）的激活。PL 在体外 VSMCs 中的处理显示出对迁移的抑制以及血小板衍生生长因子 BB（PDGF-BB）诱导的增殖，与体内发现的结果一致。我们进一步确定 PL 抑制 PDGF-BB 诱导的 PDGF 受体β激活，并抑制下游信号分子，如磷脂酶 Cγ1、细胞外信号调节激酶 1 和 2 和 Akt。最后，PL 显著减弱了 PDGF-BB 刺激后 PDGF 受体信号转导中 NF-κB-下游转录调节剂的激活。总之，我们的研究结果表明，PL 通过一种新的治疗机制抑制体内动脉粥样硬化斑块的形成。
