Mechanism Study Of Andrographolide On Inflammation

NF-κB is a central transcriptional factor and a pleiotropic regulatorof many genes involved in immunological responses. During the screeningof a plant extract library of traditional Chinese herbal medicines, wefound that andrographolide (Andro) inhibited NF-κB activation.Mechanistically, it covalently modified reduced cysteine62 of p50, thusblocking the binding of NF-κB oligonucleotide to nuclear proteins.Andro suppressed the activation of NF-κB in stimulated endothelial cells,which reduced the expression of cell adhesion molecule E-selectin andprevented the E-selectin mediated adhesion of leukocytes under flow. Italso abrogated the peritoneal deposition of leukocytes triggered by tumornecrosis factor-α, interleukin-1βor bacterial lipopolysaccharide,prevented endotoxin induced shock, and attenuated allergic airwayinflammation in vivo. Notably, it had no suppressive effects on IκBαdegradation, p50 and p65 nuclear translocation and cell growth rates.Taken together, our results implicate the therapeutic potential of Androfor treating inflammatory disorders. Based on these results, we aresearching for better anti-inflammation compounds from Andro derivants.