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

• Published in: The Journal of surgical research 2013-11, Vol.185 (1), p.399-409
• Main Authors: Song, Bocui, PhD, Guan, Shuang, PhD, Lu, Jing, PhD, Chen, Zhibao, PhD, Huang, Guoren, MD, Li, Gen, BD, Xiong, Ying, MD, Zhang, Shuang, MD, Yue, Zhanpeng, PhD, Deng, Xuming, PhD
• Format: Article
• Language: English
• Subjects: Animals; CD4+/CD8; CD4-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - drug effects; Cell Proliferation - drug effects; Cycle; Cytokines; Dose-Response Relationship, Drug; DTH; Fisetin; Flavonoids - chemistry; Flavonoids - pharmacology; Graft Rejection - drug therapy; Graft Rejection - immunology; Hypersensitivity, Delayed - drug therapy; Hypersensitivity, Delayed - immunology; Immunosuppressive Agents - chemistry; Immunosuppressive Agents - pharmacology; In Vitro Techniques; Male; Mice; Mice, Inbred BALB C; NF-kappa B - metabolism; NF-κB; NFAT; NFATC Transcription Factors - metabolism; Organ Transplantation; Spleen - cytology; Spleen - drug effects; Surgery; T-Lymphocyte Subsets - drug effects
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2013.05.093

Abstract 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 vitro and in 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 vitro , as well as its influence on T cell–mediated delayed-type hypersensitivity reaction in vivo. Results 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. Conclusions Fisetin had strong immunosuppressive activity in vitro and in vivo , suggesting a potential role for fisetin as an immunosuppressive agent.