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

AimTo investigate the anti-inflammatory activity and possible mechanism of diosgenin, and to provide some further pharmacological evidence for its clinical applications.MethodsAnti-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-α1;). Furthermore, the effects of diosgenin on TNF-α1;-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-αB)/p65 translocation and phosphorylation were determined by Western blot.ResultsDiosgenin significantly inhibited peritoneal leukocytes migration induced by zymosan A in mice when given orally once at doses of 1 and 3 mg·kg−1. Pretreatment ECV304 cells with diosgenin at concentrations of 0.1 and 1 μmol·L−1 for 5 h remarkably decreased TNF-α1;-stimulated adhesion of HL-60 to ECV304 cells in vitro, with no effect on viability of ECV304 cells. Furthermore, diosgenin inhibited TNF-α-induced overexpression of ICAM-1 both at the mRNA and protein levels, and suppressed nuclear p65 accumulation and p65 activation in ECV304 cells.ConclusionThese results suggested that diosgenin significantly inhibited leukocytes migration and adhesion, partly due to the down-regulation of ICAM-1 expression through NF-κB pathway.