DOI: 10.3724/SP.J.1009.2013.00608

Chinese Journal of Natural Medicines (中国天然药物) 2013/11:6 PP.608-615

Diosgenin inhibits tumor necrosis factor-induced tissue factor activity and expression in THP-1 cells via down-regulation of the NF-κB, Akt, and MAPK signaling pathways

AIM: To investigate whether diosgenin could modulate tissue factor (TF) procoagulation activity, expression, and related signal transduction pathways. METHODS: Human THP-1 monocytic cells were exposed to tumor necrosis factor-α (TNF-α, 10 ng·mL–1) with or without diosgenin (0.01, 0.1, and 1 μmol·L–1) for 2 h or 5 h to induce TF procoagulant activity and expression, which were determined by the simplified chromogenic assay, reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR, and Western blotting assays. In addition, the activation of the NF-κB, Akt, and MAPK signaling pathways were also measured by Western blotting. RESULTS: Diosgenin significantly inhibited TNF-α-induced TF procoagulant activity at concentrations of 0.01 to 1 μmol·L–1 with IC50 of 0.25 μmol·L–1. It also reduced protein expression and mRNA accumulation of TF dose-dependently in activated THP-1 cells. TNF-α stimulated significantly phosphorylation on Ser536 of NF-κB/p65, Ser473 of Akt at 5–15 min, and activations of IKK-β and ERK at 15–30 min. Diosgenin (1 μmol·L–1) could inhibit the phosphorylation of NF-κB/p65, IKK-β, Akt, ERK, and JNK, but had no remarkable effects on IκB and p38 phosphorylation in THP-1 cells. CONCLUSION: Diosgenin inhibits TNF-α-induced TF activity and expression in monocytes, partly due to its down-regulation of the phosphorylation of NF-κB/p65, IKK-β, Akt, ERK, and JNK.

Key words:Diosgenin,Tissue factor,Monocytes,TNF-α,Cardiovascular diseases

ReleaseDate:2014-07-21 17:04:18

Funds:National Natural Science Foundation of China (No. 81274131), a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, 2011 Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education, Graduate Student Innovation Plan of Jiangsu Province (CX09S_040Z)