Geniposide alleviates non-alcohol fatty liver disease via regulating Nrf2/AMPK/mTOR signalling pathways

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.