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 / 中国天然药物
Chinese Journal of Natural Medicines (English Ed.)
;
(6): 608-615, 2013.
Article
in English
| WPRIM
| ID: wpr-812651
ABSTRACT
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Drugs, Chinese Herbal
/
Monocytes
/
Down-Regulation
/
NF-kappa B
/
Tumor Necrosis Factor-alpha
/
MAP Kinase Signaling System
/
Diosgenin
/
Proto-Oncogene Proteins c-akt
/
Genetics
Limits:
Humans
Language:
English
Journal:
Chinese Journal of Natural Medicines (English Ed.)
Year:
2013
Type:
Article
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