Inhibitory effect and mechanism of action of sanggenon C on human polymorphonuclear leukocyte adhesion to human synovial cells.

Aim: To examine the effect of sanggenon C on human polymorphonuclear leukocyte (PMN) adhesion to human synovial cell(HSC), and explore its mechanism.

Methods: Adhesion of PMN to HSC was measured by MTT colorimetry. Cell-ELISA and RT-PCR methods were used to examine the expression of adhesion molecules ICAM-1 and VCAM-1. Activation of nuclear factor-kappa B(NF-kappaB) was measured by electrophoretic mobility shift assays(EMSA) method.

Results: Sanggenon C effectively inhibited TNF-alpha (50 kU/L for 12 h) and IL-1beta (50 kU/L for 12 h) induced adhesion of PMN to HSC (IC50 27.29 nmol/L and 54.45 nmol/L, respectively) in a concentration-dependent manner. Adhesion molecule VCAM-1 surface protein and mRNA expression induced by TNF-alpha 50 kU/L were significantly inhibited by sanggenon C, nevertheless, for ICAM-1 only surface protein expression being inhibited. The activation of NF-kappaB was also extensively inhibited by sanggenon C.

Conclusion: Sanggenon C inhibited TNF-alpha -stimulated PMN-HSC adhesion and expression of VCAM-1 by suppressing the activation of NF-kappaB.