Abstract
Non‐alcohol fatty liver disease (NAFLD) is a common disease which causes serious liver damage. Geniposide (GEN), a kind of iridoid glycoside extracted from Gardenia jasminoides fruit, has many biological effects, such as resistance to cell damage and anti‐neurodegenerative disorder. Lipid accumulation was obvious in tyloxapol‐induced liver and oil acid (OA) with palmitic acid (PA)‐induced HepG2 cells compared with the control groups while GEN improved the increasing conditions. GEN significantly lessened the total cholesterol (TC), the triglyceride (TG), low‐density lipoprotein (LDL), very low‐density lipoprotein (VLDL), myeloperoxidase (MPO), reactive oxygen species (ROS) and increased high‐density lipoprotein (HDL), superoxide dismutase (SOD) to response the oxidative stress via activating nuclear factor erythroid‐2–related factor 2 (Nrf2), haeme oxygenase (HO)‐1 and peroxisome proliferator‐activated receptor (PPAR)α which may influence the phosphorylation of adenosine 5’‐monophosphate–activated protein kinase (AMPK) signalling pathway in mice and cells. Additionally, GEN evidently decreased the contents of sterol regulatory element‐binding proteins (SREBP)‐1c, phosphorylation (P)‐mechanistic target of rapamycin complex (mTORC), P‐S6K, P‐S6 and high mobility group protein (HMGB) 1 via inhibiting the expression of phosphoinositide 3‐kinase (PI3K), and these were totally abrogated in Nrf2−/− mice. Our study firstly proved the protective effect of GEN on lipid accumulation via enhancing the ability of antioxidative stress and anti‐inflammation which were mostly depend on up‐regulating the protein expression of Nrf2/HO‐1 and AMPK signalling pathways, thereby suppressed the phosphorylation of mTORC and its related protein.
Highlights
Non-alcoholic fatty liver (NAFLD) is a disease that develops from hepatocyte steatosis or non-alcoholic steatohepatitis (NASH) to liver fibrosis even liver cancer.[1]
Non-alcohol fatty liver disease (NAFLD) occurs through non-esterified fatty acids (NEFA) catabolism to produce intrahepatic triglycerides, which are caused by mitochondrial oxidation and are exported as very low-density lipoprotein (VLDL).[4]
Geniposide was administrated to tyloxapol-induced NAFLD C57BL/6C mice and free fatty acid (FFA)-induced HepG2 cells to observe the specific mechanism of GEN on lipid accumulation
Summary
Non-alcoholic fatty liver (NAFLD) is a disease that develops from hepatocyte steatosis or non-alcoholic steatohepatitis (NASH) to liver fibrosis even liver cancer.[1]. In the process of Nrf[2] working, phosphoinositide 3-kinase (PI3K) controls the translocation[11] and glycogen synthase kinase 3β (GSK3β) degrading the activity of Nrf2.12,13 During the process of NAFLD, it often occurs a decreasing Nrf[2] and applying natural antioxidants could prevent the oxidative stress by activating Nrf[2] and related genes.[14]
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