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

JOURNAL OF HEPATOLOGY

卷:62

Article

Morrison, Martine C.^1,2,3  Liang, Wen¹  Mulder, Petra¹  Verschuren, Lars¹  Pieterman, Elsbet¹  Toet, Karin¹  Heeringa, Peter²  Wielinga, Peter Y.¹  Kooistra, Teake¹  Kleemann, Robert¹ 

[1] Netherlands Org Appl Sci Res TNO, Dept Metab Hlth Res, NL-2333 CK Leiden, Netherlands

[2] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, NL-9713 GZ Groningen, Netherlands

[3] Top Inst Food & Nutr, NL-6709 PA Wageningen, Netherlands

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

DOI  :  10.1016/j.jhep.2014.12.011

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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