Modulation of Amomum tsao-ko on lipid metabolism and gut microbiota in high-fat diet-fed mice with NAFLD

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and is frequently aggravated by gut microbiota dysbiosis. Amomum tsao-ko (ATK), a traditional medicinal herb, possesses antioxidant and anti-inflammatory activities and has demonstrated lipid-lowering effects in obesity models. In this study, aqueous extracts of ATK were fractionated by ultrafiltration using membranes of 100, 50, 10, and 3 KDa, with emphasis on the >3 KDa and <3 KDa fractions, which were evaluated for their effects on lipid accumulation, oxidative stress, and gut microbiota in high-fat diet (HFD)-induced NAFLD mice. ATK treatment significantly reduced body-weight gain, blood glucose, serum triglyceride and cholesterol concentrations, as well as hepatic triglyceride and cholesterol levels, compared with the HFD group. Histological analysis confirmed attenuated hepatic steatosis and inflammation. ATK enhanced hepatic antioxidant capacity and suppressed the expression of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Moreover, hepatic expression of lipogenic genes, such as Ppar-γ and Fatp , was downregulated by ATK treatment. Gut microbiota analysis revealed that ATK reversed HFD-induced dysbiosis, characterized by an elevated Firmicutes/Bacteroidetes ratio, and restored microbial community diversity while increasing the abundance of beneficial taxa. Both ATK and its <3 KDa fraction protected against diet-induced NAFLD by improving lipid metabolism, alleviating hepatic steatosis and oxidative inflammation, and beneficially reshaping the gut microbiota. These findings highlight the potential of ATK as a functional food ingredient for the management of NAFLD. • Ultrafiltration technique extracts Amomum tsao-ko. • Amomum tsao-ko supplementation alleviate liver injury in the liver in high-fat diet-induced mice. • Amomum tsao-ko supplementation improve gut dysbiosis in high-fat diet-induced mice.