Suppressive effects of fisetin on mice T lymphocytes in聽vitro and in聽vivo

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• 作者：Bocui Song ; Shuang Guan ; Jing Lu ; Zhibao Chen ; Guoren Huang ; Gen Li ; Ying Xiong ; Shuang Zhang ; Zhanpeng Yue ; Xuming Deng
• 关键词：Fisetin ; Cytokines ; Cycle ; CD4+/CD8+ ; NF-魏B ; NFAT ; DTH
• 刊名：Journal of Surgical Research
• 出版年：November, 2013
• 年：2013
• 卷：185
• 期：1
• 页码：399-409
• 全文大小：2234 K

文摘

Background

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聽vitro and in聽vivo.

Methods

We measured the effect of fisetin on T-lymphocyte proliferation, T-cell subsets, cell cycle progression, cytokine production, and nuclear factor activation in聽vitro, as well as its influence on T cell-mediated delayed-type hypersensitivity reaction in聽vivo.

Results

In聽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聽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聽vivo, fisetin treatment also significantly inhibited the dinitrofluorobenzene-induced delayed-type hypersensitivity reactions in mice.

Conclusions

Fisetin had strong immunosuppressive activity in聽vitro and in聽vivo, suggesting a potential role for fisetin as an immunosuppressive agent.