NF- B is a central transcriptional factor and a pleiotropic regulator of many genes involved in immunological responses. During
the screening of a plant extract library of traditional Chinese herbal medicines, we found that NF- B activity was potently
inhibited by andrographolide (Andro), an abundant component of the plant Andrographis that has been commonly used as a folk
remedy for alleviation of inflammatory disorders in Asia for millennia. Mechanistically, it formed a covalent adduct with reduced
cysteine (62) of p50, thus blocking the binding of NF- B oligonucleotide to nuclear proteins. Andro suppressed the activation of
NF- B in stimulated endothelial cells, which reduced the expression of cell adhesion molecule E-selectin and prevented E-selectin-
mediated leukocyte adhesion under flow. It also abrogated the cytokine- and endotoxin-induced peritoneal deposition of neutro-
phils, attenuated septic shock, and prevented allergic lung inflammation in vivo. Notably, it had no suppressive effect on I B
degradation, p50 and p65 nuclear translocation, or cell growth rates. Our results thus reveal a unique pharmacological mechanism
of Andro’s protective anti-inflammatory actions.