Hepatoprotective Effect of Zingerone [4-(4-Hydroxy-3- Methoxyphenyl) Butan-2-One] in Lipopolysaccharide Induced Liver Injury Mouse Model through Downregulation of Inflammatory Mediators

Lipopolysaccharide (LPS) is responsible for causing inflammation leading to septic shock or organ failure. During treatment of infection, high amount of LPS is released in blood circulation due to immediate lysis of bacteria. Since liver helps in clearing LPS from the body, hence it remains the primary target to be stimulated by LPS releasing vigorous amount of inflammatory molecules leading to liver injury. Available anti-inflammatory chemotherapy fails in such situation because it relies predominantly on specific or non specific inhibitors of cyclooxygenase enzyme activity (COX-2) with broad range of hepatic, renal and cardiovascular side effects. There is a need to replace the potential therapies targeting suppression of LPS induced inflammation with those having no or minimal side effects. Active components from dietary medicinal plants like ginger (Zingiber officinale) are potential source of non toxic antioxidant as well as anti-inflammatory molecules. In the present study, protective effect of zingerone was evaluated against inflammation induced by LPS in terms of liver histology, serum endotoxin levels, liver function markers (AST, ALT, ALP) and inflammatory mediators (malondialdehyde, reactive nitrogen intermediates, myeloperoxidase). Relative mRNA expression of LPS induced inflammatory markers TLR4, TNF-α and iNOS was also evaluated in zingerone treated and untreated groups. Hepatoprotective effect of zingerone was observed leading to significant improvement in liver histology, decreased levels of serum endotoxin levels, liver function markers and MPO, MDA, RNI. It also showed significant down regulation of mRNA expression of TLR4, TNF-α and iNOS suggesting potent anti-inflammatory activity of zingerone against P.aeruginosa LPS induced liver injury.