title: Vaticaffinol, a resveratrol tetramer, exerts more preferable immunosuppressive activity than its precursor in vitro and in vivo through multiple aspects against activated T lymphocytes.
abstract: In the present study, we aimed to investigate the immunosuppressive activity of vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, on T lymphocytes both in vitro and in vivo, and further explored its potential molecular mechanism. Resveratrol had a wide spectrum of healthy beneficial effects with multiple targets. Interestingly, its tetramer, vaticaffinol, exerted more intensive immunosuppressive activity than resveratrol. Vaticaffinol significantly inhibited T cells proliferation activated by concanavalin A (Con A) or anti-CD3 plus anti-CD28 in a dose- and time-dependent manner. It also induced Con A-activated T cells undergoing apoptosis through mitochondrial pathway. Moreover, this compound prevented cells from entering S phase and G2/M phase during T cells activation. In addition, vaticaffinol inhibited ERK and AKT signaling pathways in Con A-activated T cells. Furthermore, vaticaffinol significantly ameliorated ear swelling in a mouse model of picryl chloride-induced ear contact dermatitis in vivo. In most of the aforementioned experiments, however, resveratrol had only slight effects on the inhibition of T lymphocytes compared with vaticaffinol. Taken together, our findings suggest that vaticaffinol exerts more preferable immunosuppressive activity than its precursor resveratrol both in vitro and in vivo by affecting multiple targets against activated T cells.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Feng
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Wu
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Liu
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Guo
authors.forename: Qiong
authors.initials: Q
authors.lastname: Luo
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Tao
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Ge
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Ren-Xiang
authors.initials: RX
authors.lastname: Tan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D003877:Dermatitis, Contact / Q000188:drug therapy; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D007166:Immunosuppressive Agents; D013267:Stilbenes; C579359:vaticaffinol; D000077185:Resveratrol