OBJECTIVETo explore the mechanism of epimedium flavonoids (EF) in regulating immunosenescence via nuclear factor-kappa B (NF-kappaB) related signal transduction pathway.

METHODS(1) The apoptosis index (AI) of splenic lymphocyte in aged rats was monitored by flow cytometry, that of young rats was taken as control. (2) The differential expression profile of NF-kappaB related signals in aged rats allocated in the control group (aged rats, group A), the EF treated group (group B), the PDTC (a NF-kappaB inhibitor) treated group (group C) and the PDTC plus EF treated group (group D), was determined and the main significant molecules in them were analyzed with gene microarray of 96 genes related to NF-kappaB signal pathway.

RESULTSExcessive apoptosis of T lymphocyte cell was seen in aged rats, and it was significantly suppressed in group B and D. In group B, 73 genes were up-regulated to different extent, including 10 of the NF-kappaB/Rel/IB gene family, transduction signal molecule member of NIK/IKK/I B/Rel/NF-kappaB, NF-kappaB regulatory target genes, trans-membrane receptors, transcription factors, and receptor protein, etc. But the up-regulation on NF-kappaB gene family could not be seen in group C and that on others were also alleviated, while in the group D, the NF-kappaB gene family and its related transduction pathway were still activated to some extent. The NF-kappaB gene family showed a markedly common feature after EF intervention, either used alone or in combination with PDTC, i.e. the significant upregulated NF-kappaB1, NF-kappaB2, Rel B and I Bepsilon, and activated NIK/IKK/I B/Rel/NF-kappaB pathway.

CONCLUSIONEF can suppress the excessive apoptosis of splenic lymphocyte in aged rats and activate Rel/NF-kappaB/ I B/IKK and their signal transduction pathway to up-regulate NF-kappaB through adjusting I Bepsilon and I Balpha, which may be the essential mechanism of EF in rebuilding the immune homeostasis of T lymphocyte apoptosis and retarding immunosenescence.