Oleuropein prevents the progression of steatohepatitis to hepatic fibrosis induced by a high-fat diet in mice

Nonalcoholic steatohepatitis (NASH) is characterized by hepatocyte injury and inflammatory cell infiltration, which has been linked to peripheral insulin resistance and increased levels of triglycerides in the liver. The purposes of this study were to establish a mouse model of NASH by feeding mice a 60% high-fat diet (HFD) and to demonstrate the anti-fibrotic effects of oleuropein, which has been shown to have anti-oxidant and anti-inflammatory properties, in this HFD-induced mouse model of NASH. C57BL/6 mice were divided into three groups: a regular diet group (Chow), a HFD group and an oleuropein-supplemented HFD group (OSD), which was fed a 0.05% OSD for 6 months. The effects of oleuropein in this model were evaluated using biochemical, histological and molecular markers. The expression levels of alpha-smooth muscle actin (α-SMA)and collagen type I in the HFD and OSD groups were evaluated using real-time PCR and western blotting. The body weight, biochemical marker levels, nonalcoholic fatty liver disease activity score, homeostasis model of assessment-insulin resistance (HOMA-IR) and leptin levels observed in the HFD group at 9 and 12 months were higher than those observed in the Chow group. The HOMA-IR and leptin levels in the OSD group were decreased compared with the HFD group. In addition, α-SMA and collagen type I expression were decreased by oleuropein treatment. We established a NASH model induced by HFD and demonstrated that this model exhibits the histopathological features of NASH progressing to fibrosis. Our results suggest that oleuropein may be pharmacologically useful in preventing the progression of steatohepatitis and fibrosis and may be a promising agent for the treatment of NASH in humans. Eating an olive leaf extract called oleuropein could prevent organ scarring caused by inflammatory liver disease, according to a mouse study from researchers in South Korea. A team led by Seung Kew Yoon from Department of Internal Medicine and Catholic University Liver Research Center, Seoul, fed mice one of three meal plans: a regular diet, a high-fat diet, or a high-fat diet supplemented with oleuropein. The mice on the high-fat diet were obese and suffered from liver fibrosis. In contrast, the mice that also received oleuropein displayed reduced liver tissue scarring, although they had similar amounts of fat accumulation in the liver. The researchers suggest that oleuropein, which has anti-oxidant and anti-inflammatory properties, could be used to prevent the progression of fibrosis in people with nonalcoholic steatohepatitis, a common liver inflammation disorder caused by an accumlation of fat in the liver.