Mirtoselect, an anthocyanin-rich bilberry extract, attenuates non-alcoholic steatohepatitis and associated fibrosis in ApoE*3Leiden miceMorrison, 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.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||7|
|Journal||Journal of Hepatology|
|Publication status||Published - May-2015|
- 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