• Ruiting Han, Huihui Qiu, Jing Zhong, Ningning Zheng, Bingbing Li, Ying Hong, Junli Ma, Gaosong Wu, Linlin Chen, Lili Sheng, and Houkai Li.
• Functional Metabolomics and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Biomedical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, China.
• Phytomedicine. 2021 May 1; 85: 153544.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with few therapeutic options available currently. Traditional Chinese Medicine (TCM) has been practiced for thousands of years in China and Asian countries, and regarded as an important source for identifying novel medicines for diseases. Si Miao Formula (SMF) is a classical TCM formula for the treatment of gout disease by reducing serum uric acid concentrations, while high concentration of uric acid is also an independent risk factor for NAFLD.PurposeTo investigate the protective effect of SMF on NAFLD in a mouse model induced by a high fat/high sucrose (HFHS) diet.MethodsMice received a HFHS diet over a 16-week period to induce NAFLD with or without SMF intervention. Lipid levels were measured in both the liver and serum. Histopathological staining was used to evaluate the extent of hepatic lipid accumulation. Liver transcriptomics was used to enrich differentially expressed genes and to predict regulatory pathways after gene set enrichment analysis. 16S rRNA gene sequencing was used to determine the microbial composition. Genes of liver lipid metabolism, inflammation and intestinal tight junctions were detected by qRT-PCR analysis.ResultsSMF attenuated hepatic steatosis, reduced body weight gain and lipid concentrations, improved sensitivity to insulin and also tolerance to glucose, in mice fed an HFHS diet. Hepatic transcriptomics showed that SMF downregulated the biosynthesis of fatty acids and stimulated the insulin secretion pathway. SMF significantly altered the gut microbiota composition and in particular increased the proportion of Akkermansia muciniphila. In agreement with liver transcriptomics, SMF downregulated the expression of genes implicated in the metabolism of lipids (Acly, Fas, Acc, Scd-1) and pro-inflammatory cytokines (Il-1β, Nlrp-3) in the livers.ConclusionThe results indicate that SMF attenuates HFHS diet-induced NAFLD and regulates hepatic lipid metabolism pathways. The anti-NAFLD effect of SMF was linked to modulation of the gut microbiota composition and in particular an increased relative abundance of Akkermansia muciniphila.Copyright © 2021 Elsevier GmbH. All rights reserved.

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