The Combination of Berberine, Tocotrienols and Coffee Extracts Improves Metabolic Profile and Liver Steatosis by the Modulation of Gut Microbiota and Hepatic miR-122 and miR-34a Expression in Mice

Nutrients. 2021 Apr 13;13(4):1281. doi: 10.3390/nu13041281.

Abstract

Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora, on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight (p < 0.01), amelioration of insulin-sensitivity (p = 0.021), total cholesterol (p = 0.014), low-density-lipoprotein-cholesterol (p < 0.001), alanine-aminotransferase (p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome.

Keywords: NAFLD; gut microbiome; insulin resistance; metabolic syndrome; miR-122; miR-34a.

MeSH terms

  • Animals
  • Arecaceae / chemistry
  • Berberine / administration & dosage
  • Berberis / chemistry
  • Coffea / chemistry
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Dysbiosis / drug therapy*
  • Dysbiosis / immunology
  • Dysbiosis / microbiology
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / immunology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Humans
  • Insulin Resistance / immunology
  • Liver / drug effects*
  • Liver / pathology
  • Male
  • Mice
  • MicroRNAs / metabolism
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / immunology
  • Non-alcoholic Fatty Liver Disease / pathology
  • Plant Extracts / administration & dosage*
  • Plant Extracts / chemistry
  • Tocotrienols / administration & dosage

Substances

  • MIRN34a microRNA, mouse
  • MicroRNAs
  • Mirn122 microRNA, mouse
  • Plant Extracts
  • Tocotrienols
  • Berberine