Ginger essential oil prevents NASH progression by blocking the NLRP3 inflammasome and remodeling the gut microbiota-LPS-TLR4 pathway in mice

Nutr Diabetes. 2024 Aug 16;14(1):65. doi: 10.1038/s41387-024-00306-1.

Abstract

Background: Diet and gut microbiota contribute to non-alcoholic steatohepatitis (NASH) progression. High-fat diets (HFDs) change gut microbiota compositions, induce gut dysbiosis, and intestinal barrier leakage, which facilitates portal influx of pathogen-associated molecular patterns including lipopolysaccharides (LPS) to the liver and triggers inflammation in NASH. Current therapeutic drugs for NASH have adverse side effects; however, several foods and herbs that exhibit hepatoprotection could be an alternative method to prevent NASH.

Methods: We investigated ginger essential oil (GEO) against palm oil-containing HFDs in LPS-injected murine NASH model.

Results: GEO reduced plasma alanine aminotransferase levels and hepatic pro-inflammatory cytokine levels; and increased antioxidant catalase, glutathione reductase, and glutathione levels to prevent NASH. GEO alleviated hepatic inflammation through mediated NLR family pyrin domain-containing 3 (NLRP3) inflammasome and LPS/Toll-like receptor four (TLR4) signaling pathways. GEO further increased beneficial bacterial abundance and reduced NASH-associated bacterial abundance.

Conclusion: This study demonstrated that GEO prevents NASH progression which is probably associated with the alterations of gut microbiota and inhibition of the LPS/TLR4/NF-κB pathway. Hence, GEO may offer a promising application as a dietary supplement for the prevention of NASH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Disease Progression
  • Gastrointestinal Microbiome* / drug effects
  • Inflammasomes* / drug effects
  • Inflammasomes* / metabolism
  • Lipopolysaccharides*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Non-alcoholic Fatty Liver Disease* / prevention & control
  • Oils, Volatile* / pharmacology
  • Oils, Volatile* / therapeutic use
  • Signal Transduction* / drug effects
  • Toll-Like Receptor 4* / metabolism
  • Zingiber officinale*

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Toll-Like Receptor 4
  • Oils, Volatile
  • Lipopolysaccharides
  • Inflammasomes
  • Nlrp3 protein, mouse
  • Tlr4 protein, mouse