SIRT1/NF kappa B pathway mediates anti-inflammatory and anti-apoptotic effects of rosmarinic acid on in a mouse model of nonalcoholic steatohepatitis (NASH)

Nonalcoholic steatohepatitis (NASH) is considered as a common liver disease. SIRT1, a pivotal sensor, controls activation of metabolic, inflammatory and apoptotic pathways. Rosmarinic acid (RA) has positive effects on the liver injuries; nevertheless, its mechanisms are not completely studied. The aim of this study was to explore the role of rosmarinic acid on the pathways involved by SIRT1 for amelioration of a mouse model of NASH. To do this, C57/BL6 mice were divided into four equal groups (6 in each group). Animals received saline and rosmarinic acid as the control groups. NASH was induced by methionine-choline-deficient (MCD) diet. In the NASH + RA group, Rosmarinic acid was injected daily in mice fed on an MCD diet. Rosmarinic acid decreased plasma triglyceride, cholesterol, liver Steatosis and oxidative stress. Rosmarinic acid administration also increased SIRT1, Nrf2 and PPAR alpha and decreased SREBP1c, FAS, NF kappa B and caspase3 expressions. Moreover, TNF alpha, IL6, P53, Bax/Bcl2 ratio and caspase3 expressions decreased. Our study demonstrated that remarkable effects of rosmarinic acid on the mice with NASH might be due to activation of SIRT1/Nrf2, SIRT1/NF kappa B and SIRT1/PPAR alpha pathways, which alleviate hepatic steatosis, oxidative stress, inflammation and apoptosis.