Therapeutic Role of Ursolic Acid on Ameliorating Hepatic Steatosis and Improving Metabolic Disorders in High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Rats

Abstract

BackgroundNon-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA), an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD)-induced obese non-alcoholic fatty liver disease (NAFLD) rat model.Methodology/Principal FindingsObese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR)-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress.Conclusions/SignificanceThese results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.

The differential effects of high-fat and high fructose diets on the liver of male albino rat and the proposed underlying mechanisms

“…Fat accumulation in the liver plays a critical role in the initiation and progression of NAFLD [22].…”

“…Many researchers studied the effect of high-fat diet (HFD), high-fructose diet (HFruD) and high-fructose high-fat diet (HFHF) on the liver [21,22,39]. The missing data are the comparison effect of these groups i.e.…”

The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α

“…According to previous reports [53,54,55], human liver cell line HL7702 and HepG2 were selected for NASH research and purchased from Shanghai Cell bank (Chinese Academy of Science, Shanghai, China), and cultured in DMEM with 25 mM glucose, 5 mM glutamine, 10% fetal bovine serum (FBS), 100 μg/mL penicillin and 100 μg/mL streptomycin at 37 °C under a 5% CO 2 environment. The cell concentrations were adjusted to 1 × 10 5 /mL and 200 μL was added to each cell in a 96-cell plate.…”

Ursolic acid and mechanisms of actions on adipose and muscle tissue: a systematic review

“…Ursolic acid (UA) is a pentacyclic triterpene natural compound found in the leaves, flowers and fruits of medicinal herbs such as Rosmarinus officinalis (rosemary), Ocimum basilicum (basil), Eriobotrya japonica (medlar), Eugenia jambolana (jamelão), Origanum vulgare (oregano) leaves, Eucalyptus globulus (eucalyptus) leaves and bark, Coffea arabica (coffee) leaves and Pyrus malus (apple peel) . Some of the proven biological effects of UA are anti‐inflammatory actions , antioxidant effects , anti‐carcinogenic effects , attenuation of muscle mass atrophy and muscle synthesis , thermogenesis activation and anti‐obesity effects . The main mechanisms of action of UA involve the following: the activation of uncoupling protein 1 (UCP1) and adenosine monophosphate ratio (AMP)‐activated protein kinase (AMPK) in adipose tissue, the reduction of the atrogin and muscle ring‐finger protein‐1 (MuRF1) in skeletal muscle, and a greater release of growth hormone and insulin‐like factor 1 (IGF‐1) into the bloodstream, as well as increased muscle protein kinase B (PKB/Akt) and mammalian target of rapamycin (mTOR).…”