Inhibition of NF-кB and Cox-2 by Lirioresinol B Dimethyl Ether in DEN induced Hepatic Fibrosis Mouse Model

Abstract

Cancer is a major public health problem and the second leading cause of mortality around the world. Hepatocellular carcinoma (HCC) is one of the most common cancers, associated with high mortality. Almost 80% of HCC cases are associated with chronic hepatitis and cirrhosis resulting from inflammation and fibrosis. Therefore, novel therapeutic agents with multifactorial effects are urgently needed for the treatment of chronic hepatitis and prevention of other hepatic diseases. Lirioresinol B Dimethyl ether (LBDE) is a bioactive phytochemical obtained from seed oil of Magnolia Fargesii, with anti-inflammatory activity. In this study, Balb/c mice were used to induce hepatic fibrosis by administration of diethyl nitrosamine (DEN) and carbon tetra chloride (CCl4) for a period of 10 weeks, followed by treatment with LBDE and 5-flourouracil (5-FU, as a positive control). The histopathological examination revealed that LBDE treatment recovered fibrosis was at week 14, while mice treated with only DEN/CCl4 had severe fibrotic liver. Furthermore, the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP) in serum significantly increased in DEN/CCl4 model group as compared with the control. The serum levels of LBDE and 5-FU were decreased and were more towards the normal range. Treatment with 5-FU showed a significant decrease in the lipid peroxidation as confirmed by decrease concentration of malondialdehyde and increase in antioxidant enzymes such as super oxide dismutase and reduced glutathione. Increased level of antioxidants in liver of LBDE and 5-FU treated group indicated the healing of hepatocytes as compared to DEN/CCL4 group. The immunoblot analysis revealed inhibition of COX-2 and NFҡB by LBDE as indicated by western blot analysis. Our result confirmed the potential therapeutic role of LBDE for the treatment and prevention of hepatic diseases