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.

Valentina Cossiga,Valeria D’Argenio,Francesco Beguinot,Paola Mirra,Filomena Morisco,Vincenzo Lembo,Nicola Caporaso,Maria Guido,Giovanna Mazzone,Iolanda Veneruso,Claudia Miele,Alessia Leone,Cecilia Nigro

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.

Highlights

In parallel to the global epidemic of obesity during the last decades, the increased prevalence of non-alcoholic fatty liver disease (NAFLD) has brought this pathology to the forefront of health care concerns [1,2]
After 1 week of acclimation the mice were divided into three groups (n = 8 each) and assigned into one of the following 24 weeks diets: (1) Standard diet (SD); (2) high fat diet (HFD); (3) HFD enriched with plant extracts (HFD+E) (140 mg/Kg/die) The HFD composition was 60% of energy derived from fats, 23% from proteins and 17% from carbohydrates, 5.6 kcal/g (Mucedola, Italy)
Our study demonstrates that the addition of the combination of plant extracts composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora to HFD induces the ame

Summary

Introduction

In parallel to the global epidemic of obesity during the last decades, the increased prevalence of non-alcoholic fatty liver disease (NAFLD) has brought this pathology to the forefront of health care concerns [1,2]. Since it has a close association with obesity and insulin resistance, NAFLD has been described as the hepatic manifestation of the metabolic syndrome [3]. Previous in vitro and in vivo studies suggest that berberine, a plant alkaloid present in Berberis Aristata, increases the expression of low-density lipoprotein (LDL) receptors and, reduces the serum levels of LDL cholesterol [9,10]. Several studies have shown that tocotrienols, the less common form of vitamin E which are present in Elaeis Guineensis, reduce cholesterol and triglyceride levels through the modulation of lipogenic genes [14,15] and improve the antioxidant defense system of the cells [16]

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