Andrographolide attenuates inflammation by inhibition of NF-κB activation through covalent modification of reduced cysteine 62 of p 50

Yi Feng Xia, Bu Qing Ye, Yi Dan Li, Jian Guo Wang, Xiang Jiu He, Xianfeng Lin, Xinsheng Yao, Dawei Ma, Arne Slungaard, Robert P Hebbel, Nigel S. Key, Jian Guo Geng

Research output: Contribution to journalArticlepeer-review

301 Scopus citations

Abstract

NF-κB 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-κB 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-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 and prevented E-selectin-mediated leukocyte adhesion under flow. It also abrogated the cytokine- and endotoxin-induced peritoneal deposition of neutrophils, attenuated septic shock, and prevented allergic lung inflammation in vivo. Notably, it had no suppressive effect on IκBα 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.

Original languageEnglish (US)
Pages (from-to)4207-4217
Number of pages11
JournalJournal of Immunology
Volume173
Issue number6
DOIs
StatePublished - Sep 15 2004

Fingerprint Dive into the research topics of 'Andrographolide attenuates inflammation by inhibition of NF-κB activation through covalent modification of reduced cysteine 62 of p <sup>50</sup>'. Together they form a unique fingerprint.

Cite this