Diosgenin reduces leukocytes adhesion and migration linked with inhibition of intercellular adhesion molecule-1 expression and NF-κB p65 activation in endothelial cells

AIM: To investigate the anti-inflammatory activity and possible mechanism of diosgenin, and to provide some further pharmacological evidence for its clinical applications. METHODS: Anti-inflammatory activities of diosgenin were evaluated by zymosan A-evoked peritoneal leukocytes migration in mice and the adhesion of human pro-myelocytic leukemia cell strain (HL-60) to human umbilical vein endothelial cell line (ECV304) cells induced by tumor necrosis factor (TNF-). Furthermore, the effects of diosgenin on TNF--induced intercellular adhesion molecule-1 (ICAM-1) expression were also investigated by reverse transcription- PCR (RT-PCR) and flow cytometric analysis, and nuclear factor-kappaB (NF-B)/p65 translocation and phosphorylation were determined by Western blot. RESULTS: Diosgenin significantly inhibited peritoneal leukocytes migration induced by zymosan A in mice when given orally once at doses of 1 and 3 mgkg1. Pretreatment ECV304 cells with diosgenin at concentrations of 0.1 and 1 molL1 for 5 h remarkably decreased TNF--stimulated adhesion of HL-60 to ECV304 cells in vitro, with no effect on viability of ECV304 cells. Furthermore, diosgenin inhibited TNF--induced overexpression of ICAM-1 both at the mRNA and protein levels, and suppressed nuclear p65 accumulation and p65 activation in ECV304 cells. CONCLUSION: These results suggested that diosgenin significantly inhibited leukocytes migration and adhesion, partly due to the down-regulation of ICAM-1 expression through NF-B pathway.