Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, People's Republic of China.
J Surg Res. 2013 Nov;185(1):399-409. doi: 10.1016/j.jss.2013.05.093. Epub 2013 Jun 19.
Most of the immunosuppressive drugs have satisfactory therapeutic effects on organ transplantation and autoimmune disease. However, their clinical application is limited by side effects. Therefore, new and safe immunosuppressive drugs against acute and chronic rejections are eagerly awaited. Fisetin, a flavonoid present in various types of vegetables and fruits, has few side effects and low level of toxicity, which would be a desirable clinical feature. In the present study, we investigated the immunosuppressive effects and underlying mechanisms of fisetin against T-cell activation in vitro and in vivo.
We measured the effect of fisetin on T-lymphocyte proliferation, T-cell subsets, cell cycle progression, cytokine production, and nuclear factor activation in vitro, as well as its influence on T cell-mediated delayed-type hypersensitivity reaction in vivo.
In vitro, the results showed that fisetin significantly suppressed mouse splenocytes proliferation, Th1 and Th2 cytokine production, cell cycle and the ratio of CD4(+)/CD8(+) T cells. Furthermore, fisetin exerts an immunosuppressive effect in mouse T lymphocytes through the suppression of nuclear factor kappa B activation and nuclear factor of activated T cells signaling in a dose-dependent manner. In vivo, fisetin treatment also significantly inhibited the dinitrofluorobenzene-induced delayed-type hypersensitivity reactions in mice.
Fisetin had strong immunosuppressive activity in vitro and in vivo, suggesting a potential role for fisetin as an immunosuppressive agent.
大多数免疫抑制剂在器官移植和自身免疫性疾病方面具有满意的治疗效果。然而，它们的临床应用受到副作用的限制。因此，新的和安全的免疫抑制剂，针对急性和慢性排斥反应，正在急切期待中。漆黄素是一种存在于各种蔬菜和水果中的类黄酮，副作用小，毒性低，这将是一个理想的临床特征。在本研究中，我们研究了漆黄素在体外和体内对 T 细胞活化的免疫抑制作用及其潜在机制。
我们测量了漆黄素对 T 淋巴细胞增殖、T 细胞亚群、细胞周期进程、细胞因子产生和核因子激活的影响，以及其对体内 T 细胞介导的迟发型超敏反应的影响。
在体外，结果表明漆黄素显著抑制了小鼠脾细胞的增殖、Th1 和 Th2 细胞因子的产生、细胞周期和 CD4(+)/CD8(+) T 细胞的比例。此外，漆黄素通过抑制核因子 kappa B 激活和活化 T 细胞核因子信号通路，以剂量依赖的方式发挥对小鼠 T 淋巴细胞的免疫抑制作用。在体内，漆黄素治疗也显著抑制了二硝基氟苯诱导的小鼠迟发型超敏反应。
漆黄素在体内和体外均具有很强的免疫抑制活性，提示漆黄素可能作为一种免疫抑制剂发挥作用。
