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

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, facilitating portal influx of pathogen-associated molecular patterns including lipopolysaccharides (LPS) to the liver and triggering 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: 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.

Suraphan Panyod, Wei-Kai Wu, Ya-Chi Hsieh, Yea-Jing Tseng, Sin-Yi Peng, Rou-An Chen, Huai-Syuan Huang, Yi-Hsun Chen, Ting-Chin David Shen, Chi-Tang Ho, Chun-Jen Liu, Hsiao-Li Chuang, Chi-Chang Huang, Ming-Shiang Wu, Lee-Yan Sheen