Another SAR131675 inflammatory enzyme COX-2 is also activated by LPS stimulus. Previous reports have shown a potential role of tyrosine kinase in LPS promoter region that contain 24 transcriptional factor- binding sites, including those for nuclear factor-kB family, that appears to be essential in the enhanced COX-2 gene expression seen in macrophages exposed to endotoxin. Cyclooxygenase-2 is an inducible enzyme of macrophages catalyzing the conversion of arachidonic acid to prostaglandins. Recent studies have suggested that increased levels of prostaglandins and cyclooxygenase activity and COX-2-derived bioactive lipids, including prostaglandin E2, are potent inflammatory mediators causing tissue injury. LPS induced very high mRNA expression of COX-2 and this probably may have led to increased production of prostaglandin E2 resulting in intense inflammation. Zingerone treatment significantly reduced mRNA expression of COX-2 which ultimately reduced the liver injury in treated animals. RelA, NF-kB2 are signaling molecules and regulate the expression of many inflammatory genes. Expression of these genes in the present study clearly indicated that these genes are involved in the signaling cascade and regulation of expression of inflammatory genes. Rel A and NF-kB2 gene expression was found to increase following LPS administration. Zingerone treatment significantly inhibited the expression level of these genes clearly indicating that zingerone was able to interfere with inter signaling pathways and suppress the hyper expression of important cell signaling molecules. Since, P.aeruginosa LPS showed maximum expression of all genes at 8 hour interval, this time period was chosen for observing the effect of zingerone on the expression of inflammatory markers. Expression of COX-2, TNF-a, iNOS, RelA, NFkB2 and TLR4 was found to be highly suppressed by zingerone treatment at 8 h interval. Decrease in the mRNA expression levels in presence of zingerone indicated low amount of mRNA in the liver leading to decrease in protein levels with minimum LPS induced hepatotoxic effect. Zingerone has been found to be successful in reducing inflammation through multitargeted mechanism. In addition to free radical scavenging effects, reducing binding efficiently of LPS to LPS receptors and further interference with the activation of inflammatory signalling molecules. Results of the present study suggest that zingerone inhibited LPSinduced acute liver injury which was mediated via TLR4/NF-kB signaling pathway by suppressing the mRNA expression of inflammatory markers involved in this pathway. We hypothesize that zingerone may have altered the endotoxin receptor complex formation since ginger components particularly shogaols are known to inhibit TLR4 dimerization. Hence it may also have the potential to inhibit TLR4 dimerization or TLR4 and MD-2 complex formation. Both steps are necessary for the downstream signalling of the endotoxin induced expression of genes. The present study provides an insight on the impact of zingerone in suppressing inflammatory mediator production, reducing oxidative damage to liver tissue hence protecting liver from endotoxin induced injury.