Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Department of Dermatology, Taipei Medical University Hospital and Department of Dermatology, Taipei Medical University-Shuang Ho Hospital, Taipei 11031, Taiwan.
Phytomedicine. 2012 Feb 15;19(3-4):270-7. doi: 10.1016/j.phymed.2011.11.012. Epub 2012 Jan 11.
There is much evidence indicating that human leukemic cells and monocytes/macrophages synthesize, and secrete, several matrix metalloproteinases (MMPs), and participate in the degradation of extracellular matrix components in tissue lesions. In this study, we investigated the effects and mechanisms of andrographolide, extracted from the herb Andrographis paniculata, on human monocytic MMPs expression and activation. Andrographolide (1-50 μM) exhibited concentration-dependent inhibition of MMP-9 activation, induced by either tumor necrosis factor-α (TNF-α), or lipopolysaccharide (LPS), in THP-1cells. In addition, andrographolide did not present an inhibitory effect on MMP-9 enzymatic activity at a concentration of 50 μM. By contrast, enzyme-linked immunosorbent assay (ELISA) showed that andrographolide partially affect TIMP-1 levels. Western blot analysis showed that both TNF-α, and LPS stimulators attenuated MMP-9 protein expression in a concentration-dependent manner. Using reverse transcription polymerase chain reaction (RT-PCR), we found that andrographolide suppressed expression of MMP-9 messenger RNA. Furthermore, we also found that andrographolide could significantly inhibit the degradation of inhibitor-κB-α (IκB-α) induced by TNF-α. We used electrophoretic mobility shift assay and reporter gene detection to show that andrographolide also markedly inhibited NF-κB signaling, anti-translocation and anti-activation. In conclusion, we demonstrate that andrographolide attenuates MMP-9 expression, and its main mechanism might involve the NF-κB signal pathway. These results provide new opportunities for the development of new anti-inflammatory and leukemic therapies.
有大量证据表明，人类白血病细胞和单核细胞/巨噬细胞合成并分泌多种基质金属蛋白酶（MMPs），并参与组织损伤中外源性基质成分的降解。在这项研究中，我们研究了穿心莲内酯（从穿心莲植物中提取）对人单核细胞 MMPs 表达和激活的影响及其机制。穿心莲内酯（1-50 μM）浓度依赖性地抑制 TNF-α或 LPS 诱导的 THP-1 细胞 MMP-9 的激活。此外，穿心莲内酯在 50 μM 的浓度下对 MMP-9 的酶活性没有抑制作用。相比之下，酶联免疫吸附测定（ELISA）表明穿心莲内酯部分影响 TIMP-1 水平。Western blot 分析表明，TNF-α和 LPS 刺激物均以浓度依赖性方式减弱 MMP-9 蛋白表达。通过逆转录聚合酶链反应（RT-PCR），我们发现穿心莲内酯抑制 MMP-9 信使 RNA 的表达。此外，我们还发现穿心莲内酯可以显著抑制 TNF-α诱导的 IκB-α（IκB-α）的降解。我们使用电泳迁移率变动分析和报告基因检测表明，穿心莲内酯还显著抑制 NF-κB 信号转导、反式易位和反式激活。总之，我们证明穿心莲内酯减弱 MMP-9 的表达，其主要机制可能涉及 NF-κB 信号通路。这些结果为开发新的抗炎和白血病治疗方法提供了新的机会。
