Niu Xinli, Huang Zhihong, Zhang Lin, Ren Xuequn, Wang Junpeng
College of Life Science, Henan University, Kaifeng 475004, China.
College of Nursing, Henan University, Kaifeng 475004, China.
Eur J Pharmacol. 2015 Mar 5;750:8-13. doi: 10.1016/j.ejphar.2015.01.017. Epub 2015 Jan 22.
Auraptene, a citrus fruit-derived coumarin, has been reported to exert valuable pharmacological properties as anti-tumor, anti-inflammatory, and anti-oxidant agent. However, little is known about auraptene on immune responses. In this study, we conducted an investigation to evaluate auraptene as an anti-T lymphocyte proliferation agent using CD3/CD28-activated lymphocytes isolated from C57BL/6 mice. We found that administration of auraptene inhibited CD3/CD28-activated lymphocyte proliferation in a dose dependent manner, but the inhibition at a wide range of doses used in this study did not induce cytotoxicity or apoptosis. In addition, auraptene dose dependently decreased the CD3/CD28-activated T lymphocyte secreting T helper (Th)1 cytokines (interleukin (IL)-2 and interferon (IFN)-γ); whereas, auraptene could decrease Th2 cytokine (IL-4) at a higher level (40µM) but had not at lower levels (10 and 20µM). Further mechanistic study demonstrated that auraptene doses dependently suppressed T cell early and middle/late activation marker CD69 and CD25 expression, respectively. Finally, auraptene could suppress cell cycle progression which contributes to inhibiting T cell proliferation and cell division. These findings indicate that auraptene exhibits anti-inflammatory properties via inhibiting T cell proliferation and their inflammatory cytokine secretion that may mediate the interaction between T cells and autoimmune disorders, suggesting that auraptene is a potential food-derived compound with a benefit to those with abnormally over-activation T cell mediated response and chronic inflammation such as autoimmune and inflammatory diseases.
奥瑞烯醇是一种源自柑橘类水果的香豆素，据报道具有抗肿瘤、抗炎和抗氧化等重要药理特性。然而，关于奥瑞烯醇对免疫反应的影响却知之甚少。在本研究中，我们使用从C57BL/6小鼠分离的经CD3/CD28激活的淋巴细胞，对奥瑞烯醇作为抗T淋巴细胞增殖剂进行了评估。我们发现，给予奥瑞烯醇能以剂量依赖性方式抑制经CD3/CD28激活的淋巴细胞增殖，但在本研究中使用的广泛剂量范围内的抑制作用并未诱导细胞毒性或凋亡。此外，奥瑞烯醇剂量依赖性地降低了经CD3/CD28激活的T淋巴细胞分泌辅助性T细胞（Th）1细胞因子（白细胞介素（IL）-2和干扰素（IFN）-γ）；然而，奥瑞烯醇在较高水平（40µM）时可降低Th2细胞因子（IL-4），但在较低水平（10和20µM）时则无此作用。进一步的机制研究表明，奥瑞烯醇剂量依赖性地分别抑制T细胞早期和中/晚期激活标志物CD69和CD25的表达。最后，奥瑞烯醇可抑制细胞周期进程，这有助于抑制T细胞增殖和细胞分裂。这些发现表明，奥瑞烯醇通过抑制T细胞增殖及其炎性细胞因子分泌而表现出抗炎特性，这可能介导了T细胞与自身免疫性疾病之间的相互作用，提示奥瑞烯醇是一种潜在的源自食物的化合物，对那些T细胞介导的反应异常过度激活和患有慢性炎症如自身免疫性疾病和炎性疾病的人有益。
