Following zingerone treatment proinflammatory cytokines also showed significantly low levels. Anti-inflammatory activity of zingerone in this study, could be attributed to phenolic nature of zingerone which might have led to scavenging of free radicals. Methoxy group with phenolic hydroxyl group in zingerone facilitates proton release along with long chain ethyl methyl ketone group providing bulk stabilization to zingerone molecule. This may lead to cell penetration and scavenging of free radicals. Anti-inflammatory potential of zingerone treatment along with antibiotic therapy showed decrease in inflammatory response in terms of decreased neutrophilic granulocyte infiltration and no hepatic portal haemorrhage. Hepatic haemorrhage was also absent in zingerone treated liver tissue. Levels of Inflammatory mediators MDA, RNI and MPO in zingerone treated animals were also significantly reduced. A significant body of evidence indicates that Injury by LPS particularly in liver involves LPS binding proteins which activate the CD14/TLR4 receptor and in turn induce transduction of inflammatory signals resulting in the regulation of inflammatory mediator production. Inflammatory markers chosen for the study have been found to play significant role in LPS in vivo induced tissue injury through NF-kB. Time dependent CPI-613 expression of genes induced by LPS revealed that expression of some genes started early at a time interval of 4 h and some at 8 h. Level of expression was found to be variable but maximum expression was found at 8 h. In the present study, P.aeruginosa LPS significantly enhanced mRNA expression of TLR4 receptor leading to increase in the number of TLR4 receptors on the liver cell surface. Due to this, more binding of LPS to cells resulting in potent induction of inflammatory response was observed. Zingerone treatment significantly reduced the level of mRNA expression of TLR4 receptor indicating reduced number of TLR4 receptors and thereby less binding of LPS. This may have led to decreased inflammatory response after zingerone treatment. During gram-negative sepsis, LPS induced cells are triggered to produce large quantities of pro-inflammatory cytokines such as tumor necrosis factor alpha in response to endotoxin. TNF-a is secreted by a variety of cells, including hepatocytes, kupffer cells mast cells and epidermal cells. However, mainly activating macrophages and natural killer cells, release potent biologically active substances which cause shock, fever, organ failure and other pathophysiological implications Workers have also found that TNF-a plays a crucial role in LPS-induced liver injury leading to hepatotoxicity. In the present study, LPS caused tremendous increase in TNF- a levels at 4 h and 8 h after LPS administration in liver tissue indicating that its production is mainly responsible for liver injury. Zingerone treated liver cells showed significantly low levels of TNF- a suggesting less hepatotoxicity and tissue inflammation. We also checked the mRNA expression levels for iNOS gene. Hyper expression of iNOS clearly indicated that oxidative damage to the liver is contributed by iNOS. iNOS expression is known to be enhanced by LPS leading to generation of nitric oxide radicals causing acute tissue injury.