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

Abstract

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.

Downregulation of microRNA-451 in non-alcoholic steatohepatitis inhibits fatty acid-induced proinflammatory cytokine production through the AMPK/AKT pathway

“…The NAFLD mouse model was established successfully after feeding a 58% HFD for 3 months (NAFLD) and 9 months (NASH) and confirmed by an independent pathologist. Our treatment result was consistent with previous reports (Kim et al, 2014). This was determined by H&E (Fig.…”

“…The current understanding of the development and progression of NAFLD is encapsulated by a multistep process associated with hepatic steatosis, innate immune activation, inflammation, apoptosis and progressive liver damage. Our previous studies have shown that a mouse model of NAFLD, which was successfully established in C57BL/6 mice by HFD feeding exhibited morbid obesity with increased liver damage and collagen accumulation over time (Kim et al, 2014). In this study, the systematic investigation of cDNA expression profiling between hepatic steatosis and NASH was performed to explore the cellular mechanisms in the development of NASH.…”

“…To investigate the molecular mechanisms underlying the progression of NAFLD, it is essential to develop appropriate in vitro and in vivo models. We previously established a high fat diet (HFD)-induced NAFLD mouse model that exhibits pathological features similar to those in humans (Kim et al, 2014). In addition, we developed an in vitro model of hepatocytic steatosis in a HepG2 cell line exposed to palmitate (PA).…”

“…In addition, we developed an in vitro model of hepatocytic steatosis in a HepG2 cell line exposed to palmitate (PA). We also showed the preventive and therapeutic effects of oleuropein, a secoiridoid derived from olives (Olea europaea), on the progression of hepatic fibrosis from steatohepatitis in these experimental models (Hur et al, 2012;Kim et al, 2014;Park et al, 2011).…”

The Hepatoprotective Effect of Olive Leaf Extract on Diabetic Pregnant Mice and Their Fetuses

“…ISSN 2157-6076 2017 The treatment of pregnant mice with olive leaf extract (GIV) caused a detectable decrease of the transaminases activity thus improving hepatic function. Similar results were reported by many authors who suggested that oleuropein had hepatoprotective effects (Domitrovic et al, 2012;Eidi et al, 2009;Kim et al, 2014;Mousa et al, 2014). Also, the histopathological findings support the hepatoprotection of olive leaf extract where, the treatment of diabetic group with OLE (GIV) improved the histological architecture with existents of the cytoplasmic vacuoles in some hepatocytes this could be due to antioxidative stress or anticitotoxic effect of the olive leaf extracts.…”