Total flavonoids of Broussonetia papyrifera alleviate non-alcohol fatty liver disease via regulating Nrf2/AMPK/mTOR signaling pathways

Biochim Biophys Acta Mol Cell Biol Lipids. 2024 Jun;1869(5):159497. doi: 10.1016/j.bbalip.2024.159497. Epub 2024 Apr 20.

Abstract

Backgrounds: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases. The leaves of Broussonetia papyrifera contain a large number of flavonoids, which have a variety of biological functions.

Methods: In vitro experiments, free fatty acids were used to stimulate HepG2 cells. NAFLD model was established in vivo in mice fed with high fat diet (HFD) or intraperitoneally injected with Tyloxapol (Ty). At the same time, Total flavonoids of Broussonetia papyrifera (TFBP) was used to interfere with HepG2 cells or mice.

Results: The results showed that TFBP significantly decreased the lipid accumulation induced by oil acid (OA) with palmitic acid (PA) in HepG2 cells. TFBP decreased the total cholesterol (TC), the triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDLC) in serum. TFBP could also effectively inhibit the generation of reactive oxygen species (ROS) and restrained the level of myeloperoxidase (MPO), and enhance the activity of superoxide dismutase (SOD) to alleviate the injury from oxidative stress in the liver. Additionally, TFBP activated nuclear factor erythroid-2-related factor 2 (Nrf2) pathway to increasing the phosphorylation of AMP-activated protein kinase (AMPK). Meanwhile, protein levels of mTORC signaling pathway were evidently restrained with the treatment of TFBP.

Conclusion: Our experiments proved that TFBP has the therapeutic effect in NAFLD, and the activation of Nrf2 and AMPK signaling pathways should make sense.

Keywords: AMPK; Broussonetia papyrifera; Flavonoids; Lipid accumulation; NAFLD; Nrf2; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases* / metabolism
  • Animals
  • Broussonetia* / chemistry
  • Diet, High-Fat / adverse effects
  • Flavonoids* / pharmacology
  • Hep G2 Cells
  • Humans
  • Lipid Metabolism / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2* / metabolism
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction* / drug effects
  • TOR Serine-Threonine Kinases* / metabolism

Substances

  • NF-E2-Related Factor 2
  • Flavonoids
  • AMP-Activated Protein Kinases
  • TOR Serine-Threonine Kinases
  • NFE2L2 protein, human
  • Reactive Oxygen Species