Department of Cardiology, First Affiliated Hospital of Soochow University, Soochow, China.
Basic Clin Pharmacol Toxicol. 2010 Aug;107(2):637-42. doi: 10.1111/j.1742-7843.2010.00548.x. Epub 2010 Mar 22.
Puerarin (4'-7-dihydroxy-8-beta-D-glucosylisoflavone), the most abundant isoflavone-C-glucoside extracted from the root of the plant Pueraria lobata, has demonstrated anti-inflammatory activity in cellular models of inflammation. In this report, we examined the ability of puerarin to modulate C-reactive protein (CRP) expression and key molecules in the nuclear factor kappa B (NF-kappaB) pathway to determine its molecular target. The protein and mRNA levels of CRP were determined in lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells of patients with unstable angina pectoris. Also, we detected the I-kappaBalpha phosphorylation and the p65NF-kappaB expression in peripheral blood mononuclear cells under our experimental condition. The results indicated that puerarin inhibited the expression of the protein and mRNA levels of CRP in LPS-induced peripheral blood mononuclear cells. Subsequently, we determined that the inhibition of CRP expression was because of a dose-dependent inhibition of phosphorylation and degradation of inhibitor kappaB(I-kappaB), which resulted in a reduction of p65NF-kappaB nuclear translocation. We conclude that puerarin acts as an anti-inflammatory agent by blocking NF-kappaB signalling, and may possibly be developed as a useful agent for the chemoprevention of atherosclerosis.
葛根素(4'-7-二羟基-8-β-D-葡萄糖基异黄酮),是从植物野葛的根部提取的最丰富的异黄酮-C-葡萄糖苷,已在炎症的细胞模型中显示出抗炎活性。在本报告中,我们研究了葛根素调节 C 反应蛋白(CRP)表达和核因子 kappa B(NF-kappaB)途径中关键分子的能力,以确定其分子靶标。在不稳定型心绞痛患者的脂多糖(LPS)诱导的外周血单核细胞中测定 CRP 的蛋白和 mRNA 水平。此外,我们还在外周血单核细胞中检测了实验条件下 I-kappaBalpha 磷酸化和 p65NF-kappaB 表达。结果表明,葛根素抑制 LPS 诱导的外周血单核细胞中 CRP 的蛋白和 mRNA 水平表达。随后,我们确定 CRP 表达的抑制是由于抑制剂 kappaB(I-kappaB)的磷酸化和降解的剂量依赖性抑制,导致 p65NF-kappaB 核易位减少。我们的结论是,葛根素通过阻断 NF-kappaB 信号通路发挥抗炎作用,并且可能作为动脉粥样硬化化学预防的有用药物。