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.
Subject(s)
Gastrointestinal Microbiome , Inflammasomes , Lipopolysaccharides , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein , Non-alcoholic Fatty Liver Disease , Oils, Volatile , Signal Transduction , Toll-Like Receptor 4 , Zingiber officinale , Animals , Non-alcoholic Fatty Liver Disease/prevention & control , Non-alcoholic Fatty Liver Disease/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Gastrointestinal Microbiome/drug effects , Toll-Like Receptor 4/metabolism , Oils, Volatile/pharmacology , Oils, Volatile/therapeutic use , Mice , Inflammasomes/metabolism , Inflammasomes/drug effects , Male , Signal Transduction/drug effects , Diet, High-Fat/adverse effects , Disease Progression , Liver/metabolism , Liver/drug effects , Disease Models, AnimalABSTRACT
Recently, the role of the gut microbiota in diseases, including cardiovascular disease (CVD), has gained considerable research attention. Trimethylamine-N-oxide (TMAO), which is formed during Ê-carnitine metabolism, promotes the formation of atherosclerotic plaques, causing thrombosis. Here, we elucidated the anti-atherosclerotic effect and mechanism of ginger (Zingiber officinale Roscoe) essential oil (GEO) and its bioactive compound citral in Gubra Amylin NASH (GAN) diet with Ê-carnitine-induced atherosclerosis female ApoE-/- mice. Treatment with GEO at both low and high doses and citral inhibited the formation of aortic atherosclerotic lesions, improved plasma lipid profile, reduced blood sugar, improved insulin resistance, decreased plasma TMAO levels, and inhibited plasma inflammatory cytokines, especially interleukin-1ß. Additionally, GEO and citral treatment modulated gut microbiota diversity and composition by increasing the abundance of beneficial microbes and decreasing the abundance of CVD-related microbes. Overall, these results showed that GEO and citral may serve as potential dietary supplements for CVD prevention by improving gut microbiota dysbiosis.