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Ginsenosides Improve Nonalcoholic Fatty Liver Disease via Integrated Regulation of Gut Microbiota, Inflammation and Energy Homeostasis.

ABSTRACT: Ginseng, the root and rhizome of Panax ginseng C. A. Mey., is a famous herbal medicine, and its major ginsenosides exert beneficial effects on nonalcoholic fatty liver disease (NAFLD). Due to the multicomponent and multitarget features of ginsenosides, their detailed mechanisms remain unclear. This study aimed to explore the role of ginsenosides on NAFLD and the potential mechanisms mediated by the gut microbiota and related molecular processes. C57BL/6J mice were fed a high-fat diet (HFD) supplemented or not supplemented with ginsenoside extract (GE) for 12 weeks. A strategy that integrates bacterial gene sequencing, serum pharmacochemistry and network pharmacology was applied. The results showed that GE significantly alleviated HFD-induced NAFLD symptoms in a dose-dependent manner. Furthermore, GE treatment modulated the HFD-induced imbalance in the gut microbiota and alleviated dysbiosis-mediated gut leakage and metabolic endotoxemia. Additionally, 20 components were identified in the mouse plasma after the oral administration of GE, and they interacted with 82 NAFLD-related targets. A network analysis revealed that anti-inflammatory effects and regulation of the metabolic balance might be responsible for the effects of GE on NAFLD. A validation experiment was then conducted, and the results suggested that GE suppressed NF-?B/I?B signaling activation and decreased the release and mRNA levels of proinflammatory factors (TNF-?, IL-1? and IL-6). Additionally, GE promoted hepatic lipolytic genes (CPT-1a), inhibited lipogenic genes (SREBP-1c, FAS, ACC-1) and improved leptin resistance. These findings imply that the benefits of GE are involved in modulating the gut microbiota, enhancing the gut barrier function, restoring the energy balance, and alleviating metabolic inflammation. Moreover, GE might serve as a potential agent for the prevention of NAFLD through the integration of prebiotic, anti-inflammatory and energy-regulatory effects.

SUBMITTER: Liang W

PROVIDER: S-EPMC7928318 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Ginsenosides Improve Nonalcoholic Fatty Liver Disease <i>via</i> Integrated Regulation of Gut Microbiota, Inflammation and Energy Homeostasis.

Liang Wenyi W Zhou Kun K Jian Ping P Chang Zihao Z Zhang Qiunan Q Liu Yuqi Y Xiao Shuiming S Zhang Lanzhen L

Frontiers in pharmacology 20210212

Ginseng, the root and rhizome of <i>Panax ginseng</i> C. A. Mey., is a famous herbal medicine, and its major ginsenosides exert beneficial effects on nonalcoholic fatty liver disease (NAFLD). Due to the multicomponent and multitarget features of ginsenosides, their detailed mechanisms remain unclear. This study aimed to explore the role of ginsenosides on NAFLD and the potential mechanisms mediated by the gut microbiota and related molecular processes. C57BL/6J mice were fed a high-fat diet (HFD ...[more]

PMID: 33679403

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Project description:Aim: To investigate the intestinal flora of nonalcoholic fatty liver disease (NAFLD) in Chinese children and adolescents using metagenomic approach. Methods: All participants underwent magnetic resonance spectroscopy (MRS) to quantify liver fat content. Hepatic steatosis was defined as MRS proton density fat fraction (MRS-PDFF) >5%. A total of 58 children and adolescents were enrolled in this study, including 25 obese NAFLD patients, 18 obese non-NAFLD children, and 15 healthy children. Stool samples were collected and analyzed with metagenomics. We used Shannon index to reflect the alpha diversities of gut microbiota. Wilcoxon rank sum test and Kruskal-Wallis test were performed to evaluate alpha diversities between groups. At last, the differences of gut microbiota composition and functional annotations between obese with and without NAFLD and healthy children were assessed by Kruskal-Wallis test. Results: Significant differences in gut microbiota composition and functional annotations among three groups of children and adolescents have been observed. Deep sequencing of gut microbiota revealed high abundance of phylum Proteobacteria (Gammaproteobacteria) in obese NAFLD patients, comparing with the control group. Overall, obese children without NAFLD had less abundant Helicobacter and Helicobacter pylori. Compared to the control group, in obese children with NAFLD, the abundance of Bacteroidetes (Alistipes) were significantly reduced. Faecalibacterium prausnitzii was the only species representing a difference between obese children with and without NAFLD. There were not significant differences in terms of alpha diversity among three groups. Functional annotations demonstrated that several pathways were differentially enriched between groups, including metabolism of other amino acids, replication and repair, folding, sorting, degradation, and glycan biosynthesis and metabolism. Conclusion: Significantly differences are observed in gut microbiota composition and functional annotations between obese children with and without NAFLD in comparison to the healthy children group. The characteristic of gut microbiota in this study may contribute to a further understanding the gut-liver axis of pediatric NAFLD in China.

Dataset Information

Ginsenosides Improve Nonalcoholic Fatty Liver Disease via Integrated Regulation of Gut Microbiota, Inflammation and Energy Homeostasis.

Publications

Ginsenosides Improve Nonalcoholic Fatty Liver Disease <i>via</i> Integrated Regulation of Gut Microbiota, Inflammation and Energy Homeostasis.

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