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

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.

Geniposide inhibits proliferation and induces apoptosis of diffuse large B-cell lymphoma cells by inactivating the HCP5/miR-27b-3p/MET axis

“…Geniposide is an active extract from the traditional Chinese medicine "Zhizi". Previous studies have reported that geniposide plays an important role in anti-inflammatory, anti-oxidative stress and antitumor activities [5,32,33]. For instance, geniposide acts as a protective factor in hypoxia/reperfusion-related brain barrier impairment by reducing inflammation, oxidative stress, and apoptosis in vitro [32].…”

“…For instance, geniposide acts as a protective factor in hypoxia/reperfusion-related brain barrier impairment by reducing inflammation, oxidative stress, and apoptosis in vitro [32]. Geniposide protects against lipid accumulation by decreasing oxidative stress and inflammation in non-alcohol fatty liver disease (NAFLD) [33]. The antitumor effect of geniposide has been indicated in several types of human cancers [6][7][8][9][10].…”

“…The mechanisms underlying the biological roles of geniposide have been widely investigated, and several molecules, as well as signaling pathways, have been found to be regulated by geniposide. For example, geniposide alleviates NAFLD by modulating the Nrf2/AMPK/mTOR signaling pathway [33]. The TLR4/MyD88/NF-κB pathway is regulated by geniposide in several human diseases, such as diabetic cognitive impairment [34], acute liver injury [35], and HCC [7].…”

Chlorogenic Acid and Geniposide Combination Prevents NASH in Rats Fed High-fat diet via Microbiota and TLR4-LPS Pathway

“…Research also indicated that geniposide can ameliorate barrier dysfunction via AMPK-mediated inhibition of the MLCK pathway 19 . Previous studies demonstrated that geniposide has bene cial effects on liver diseases both in vivo and vitro 34,35 . The present study concludes that the action mechanism of the CG combination on NAFLD is multi-targeting.…”

A comparison of the chemical compounds in single- and co-boiled Zhi-Zi-Da-Huang decoctions with UPLC-qTOF-MS/MS and UPLC-DAD

“…ZZDHD has been extensively used for clearing heat and eliminating dampness and jaundice for many years in China, and it is further thought to have liver-protective, choleretic, and anti-in ammatory effects. A previous study has reported that geniposide could prevent hepatocyte injury [34]. Geniposide is hydrolyzed into genipin under the action of beta-D-glucosidases in intestinal bacteria, which is required for its choleretic action [35].…”