Extracts of bilberry (Vaccinium myrtillus L.) fruits improve liver steatosis and injury in mice by preventing lipid accumulation and cell death

ABSTRACT

Bilberry has been reported to have anti-oxidant and anti-inflammatory properties. We studied the effect of bilberry (Vaccinium myrtillus L.) fruits extracts (BEs) on the pathogenesis caused by lipid accumulation in fatty liver and non-alcoholic steatohepatitis (NASH). 5 μg/ml of BEs was enough to suppress lipid accumulation in the fatty liver model of the mouse hepatic AML12 cells. BEs increased cell viability and anti-oxidant capacity, presumably by activating (phosphorylating) Akt/STAT3 and inducing MnSOD/catalase. BEs also significantly reduced Rubicon and induced p62/SQSTM1, possibly contributing to reduce cellular lipids (lipophagy). When the mice were fed supplemented with BEs (5% or 10%, w/w), hepatic steatosis, injury, and hypercholesterolemia/hyperglycemia were significantly improved. Furthermore, histological and cytokine studies indicated that BEs possibly suppress hepatic inflammation (hepatitis) and fibrosis. Therefore, BEs improved liver steatosis and injury, and potentially suppress fibrosis by suppressing inflammatory response, which therefore may prevent the progression of fatty liver to NASH.

Graphical abstract

Bilberry fruits extracts suppressed hepatocyte injury caused by early fat accumulation. Therefore, bilberry is expected to be a liver-friendly food.

KEYWORDS:

• Bilberry fruits
• fatty liver
• liver injury
• non-alcoholic steatohepatitis (NASH)
• Vaccinium myrtillus

Acknowledgments

We are particularly grateful for generous donation from Mr. & Mrs. Fujikawa (to M.O.).

Author Contribution

M. O. designed and supervised the study. N. M., S. H. and M. O. wrote and revised the manuscript. S. H., Y, S. J. and H. Y. performed cell experiments. S. H. and M. O. performed animal experiments. S. H., T. S., N. M. and M. O. analyzed and discussed the results. All authors gave final approval and consented to be accountable on all matters.

Disclosure statement

No potential conflict of interest was reported by the authors.

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Additional information

Funding

This study was supported by the JSPS Grants-in-Aid for Scientific Researches (KAKENHI) [Grant Nos. 23659631 (to M.O.), 26670573 & 15H05659 (to S.H.)]. This work was also supported in part by the Grants-in-Aid for the Regional R&D Proposal-Based Program from the Northern Advancement Center for Science & Technology (NOASTEC Foundation) (to M.O.), the Takeda Science Foundation (to S.H.), a research grant from the Akiyama Life Science Foundation (to S.H.).