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

Abstract Diet and gut microbiota contribute to non-alcoholic steatohepatitis (NASH) progression. High-fat diets (HFDs) change gut microbiota compositions and induce gut dysbiosis and intestinal barrier leakage, which facilitates portal influx of pathogen-associated molecular patterns [e.g., lipopolysaccharides (LPS)] to the liver and triggers inflammation in NASH. The current therapeutic drugs for NASH have adverse side effects; however, several foods and herbs have exhibited hepatoprotection. We investigated ginger essential oil (GEO) against palm oil-containing HFDs in LPS-injected murine NASH model. GEO prevented NASH development by increasing plasma alanine aminotransferase levels; increasing antioxidant catalase, glutathione reductase, and glutathione levels; and reducing hepatic pro-inflammatory cytokine levels. GEO alleviated hepatic inflammation through mediated NLR family pyrin domain-containing 3 inflammasome and LPS/Toll-like receptor 4 signaling pathways. GEO further increased beneficial bacterial abundance and reduced NASH-associated bacterial abundance. GEO may, therefore, prevent NASH by inhibiting hepatic inflammation and modulating the gut microbiota and its metabolite-related pathway.