Protective Effect of Rosmarinic Acid on Inflammatory Changes of Hepatic Cells in Non-alcoholic Steatohepatitis in Mice: Cyclooxygenase 2/ Prostaglandin E2 Pathway

Abstract

Background and Objectives: Nonalcoholic Steatohepatitis (NASH) is one of the common liver diseases, characterized by excessive lipid accumulation (steatosis) and inflammation in the liver. Inflammation is one of main reasons for this disease which takes place from different pathways. Rosmarinic Acid (RA) is an antioxidant and anti-inflammatory product with positive effects on the improvement of liver injuries. This study aims to evaluate protective effect of RA against liver inflammation caused by NASH in male mice through affecting cyclooxygenase-2/ Prostaglandin E2 (COX-2/PEG2) pathway and Matrix Metalloproteinase-9 (MMP-9). Methods: In this study, 24 C57/BL6 male mice were used. They were divided into four groups of 6 including; Control, RA, NASH, and NASH+RA. The NASH was induced by a methionine/choline-deficient diet for 8 weeks. The RA was administrated intraperitoneally and daily for 8 weeks. After 8 weeks, the animals were sacrificed and their liver was removed. hematoxylin and eosin staining was preformed for histological evaluation and real-time PCR and ELISA assays were used for molecular studies. Results: The RA significantly reduced hepatic steatosis and inflammation as well as the expression of MMP-9 and COX-2 which led to the significant reduction of PEG2 level. Conclusion: It seems that RA can reduce liver inflammation and thereby attenuate NASH in male mice by reducing the expression of COX-2 enzyme and MMP-9 and the concentration of PEG2.

Keywords

• liver
• nonalcoholic fatty liver disease
• matrix metalloproteinase-9
• prostaglandin e2
• rosmarinic acid