Institute of Cellular Biology and Pathology Nicolae Simionescu, 8 B.P. Hasdeu Street, 050568, Bucharest, Romania.
Phytother Res. 2011 Dec;25(12):1737-42. doi: 10.1002/ptr.3463. Epub 2011 Mar 28.
Resistin is a cytokine which plays an important role in cardiovascular disease by influencing systemic inflammation and endothelial activation. In human endothelial cells (HEC) it increases the expression of P-selectin and fractalkine, and enhances monocyte adhesion by antioxidant mechanisms. This study investigated whether the natural antioxidants curcumin (CC) and an extract of Morus alba leaves (MA) have protective effects in resistin-activated HEC. HEC were exposed to 100 ng/mL resistin for 6 and 18 h in the absence or presence of MA or CC and the expression of fractalkine and P-selectin was determined by RT-PCR and western blot. Intracellular accumulation of reactive oxygen species (ROS) was monitored by fluorimetry and NADPH oxidase activity by a lucigenin-enhanced chemiluminescence assay. In addition, adhesion assays using the monocytic U937 cells were performed. The results showed that treatment of HEC exposed to resistin with MA and CC: (1) inhibited significantly P-selectin and fractalkine expression, (2) inhibited the increase in the intracellular ROS level, (3) reduced NADPH activation and (4) reduced monocytes adhesion to HEC. The results indicate that MA and curcumin target resistin-induced human endothelial activation partly via antioxidant mechanisms and suggest that they may represent therapeutic agents in vascular disease mediated by resistin.
抵抗素是一种细胞因子，通过影响全身炎症和内皮细胞激活，在心血管疾病中发挥重要作用。在人内皮细胞（HEC）中，它通过抗氧化机制增加 P-选择素和 fractalkine 的表达，并增强单核细胞黏附。本研究探讨了天然抗氧化剂姜黄素（CC）和桑叶提取物（MA）是否对抵抗素激活的 HEC 具有保护作用。HEC 在无 MA 或 CC 的情况下，或在存在 MA 或 CC 的情况下，暴露于 100ng/mL 的抵抗素 6 和 18 小时，通过 RT-PCR 和 Western blot 测定 fractalkine 和 P-选择素的表达。通过荧光法监测细胞内活性氧（ROS）的积累，通过荧光素增强化学发光测定法测定 NADPH 氧化酶活性。此外，还进行了使用单核细胞 U937 细胞的黏附实验。结果表明，用 MA 和 CC 处理暴露于抵抗素的 HEC：（1）显著抑制 P-选择素和 fractalkine 的表达，（2）抑制细胞内 ROS 水平的增加，（3）减少 NADPH 的激活，（4）减少单核细胞黏附到 HEC。结果表明，MA 和姜黄素通过抗氧化机制部分靶向抵抗素诱导的人内皮细胞激活，并表明它们可能是抵抗素介导的血管疾病的治疗剂。
