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

Morrison, M. C., Liang, W., Mulder, P., Verschuren, L., Pieterman, E., Toet, K., Heeringa, P., Wielinga, P. Y., Kooistra, T. & Kleemann, R., May-2015, In : Journal of Hepatology. 62, 5, p. 1180-1186 7 p.

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DOI

  • Martine C. Morrison
  • Wen Liang
  • Petra Mulder
  • Lars Verschuren
  • Elsbet Pieterman
  • Karin Toet
  • Peter Heeringa
  • Peter Y. Wielinga
  • Teake Kooistra
  • Robert Kleemann

Background & Aims: Anthocyanins may have beneficial effects on lipid metabolism and inflammation and are demonstrated to have hepatoprotective properties in models of restraint-stressand 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 20 weeks 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. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)1180-1186
Number of pages7
JournalJournal of Hepatology
Volume62
Issue number5
Publication statusPublished - May-2015

    Keywords

  • Anthocyanins, Bilberry, Cholesterol crystals, Fibrosis, Free cholesterol, Non-alcoholic steatohepatitis, Polyphenols, Steatosis, FATTY LIVER-DISEASE, CHOLESTEROL CRYSTALS, DIETARY-CHOLESTEROL, PLASMA-CHOLESTEROL, METABOLIC SYNDROME, DIABETIC MICE, UNITED-STATES, NASH, ATHEROSCLEROSIS, INFLAMMATION

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