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J Hepatol. 2015 May;62(5):1180-6. doi: 10.1016/j.jhep.2014.12.011. Epub 2014 Dec 13.

Mirtoselect, an anthocyanin-rich bilberry extract, attenuates non-alcoholic steatohepatitis and associated fibrosis in ApoE(∗)3Leiden mice.

Author information

1
Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Zernikedreef 9, 2333 CK Leiden, The Netherlands; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1 (EA11), 9713 GZ Groningen, The Netherlands; Top Institute Food and Nutrition, Nieuwe Kanaal 9A, 6709 PA Wageningen, The Netherlands. Electronic address: martine.morrison@tno.nl.
2
Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Zernikedreef 9, 2333 CK Leiden, The Netherlands.
3
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1 (EA11), 9713 GZ Groningen, The Netherlands.

Abstract

BACKGROUND & AIMS:

Anthocyanins may have beneficial effects on lipid metabolism and inflammation and are demonstrated to have hepatoprotective properties in models of restraint-stress- and chemically-induced liver damage. However, their potential to protect against non-alcoholic steatohepatitis (NASH) under conditions relevant for human pathogenesis remains unclear. Therefore, we studied the effects of the standardised anthocyanin-rich extract Mirtoselect on diet-induced NASH in a translational model of disease.

METHODS:

ApoE(∗)3Leiden mice were fed a Western-type cholesterol-containing diet without (HC) or with 0.1% (w/w) Mirtoselect (HCM) for 20weeks to study the effects on diet-induced NASH.

RESULTS:

Mirtoselect attenuated HC-induced hepatic steatosis, as observed by decreased macro- and microvesicular hepatocellular lipid accumulation and reduced hepatic cholesteryl ester content. This anti-steatotic effect was accompanied by local anti-inflammatory effects in liver, as demonstrated by reduced inflammatory cell clusters and reduced neutrophil infiltration in HCM. On a molecular level, HC diet significantly induced hepatic expression of pro-inflammatory genes Tnf, Emr1, Ccl2, Mpo, Cxcl1, and Cxcl2 while this induction was less pronounced or significantly decreased in HCM. A similar quenching effect was observed for HC-induced pro-fibrotic genes, Acta2 and Col1a1 and this anti-fibrotic effect of Mirtoselect was confirmed histologically. Many of the pro-inflammatory and pro-fibrotic parameters positively correlated with intrahepatic free cholesterol levels. Mirtoselect significantly reduced accumulation and crystallisation of intrahepatic free cholesterol, providing a possible mechanism for the observed hepatoprotective effects.

CONCLUSIONS:

Mirtoselect attenuates development of NASH, reducing hepatic lipid accumulation, inflammation and fibrosis, possibly mediated by local anti-inflammatory effects associated with reduced accumulation and crystallisation of intrahepatic free cholesterol.

KEYWORDS:

Anthocyanins; Bilberry; Cholesterol crystals; Fibrosis; Free cholesterol; Non-alcoholic steatohepatitis; Polyphenols; Steatosis

PMID:
25514555
DOI:
10.1016/j.jhep.2014.12.011
[Indexed for MEDLINE]
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