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

References

• Chu W-K, Cheung SCM, Lau RAW, et al. Bilberry (Vaccinium myrtillus L.). In: Benzie IFE, Wachtel-Galor S, editors Herbal Medicine: biomolecular and Clinical Aspects. Florida (FL): CRC Press; 2011. p. 55–71.
   Google Scholar
• Ferlemi AV, Lamari FN. Berry leaves: an alternative source of bioactive natural products of nutritional and medicinal value. Antioxidants. 2016;5:17.
   Web of Science ®Google Scholar
• Akerström A, Jaakola L, Bång U, et al. Effects of latitude-related factors and geographical origin on anthocyanidin concentrations in fruits of Vaccinium myrtillus L. (bilberries). J Agric Food Chem. 2010;58:11939–11945.
   PubMed Web of Science ®Google Scholar
• Burdulis D, Sarkinas A, Jasutiené I, et al. Comparative study of anthocyanin composition, antimicrobial and antioxidant activity in bilberry (Vaccinium myrtillus L.) and blueberry (Vaccinium corymbosum L.) fruits. Acta Polym Pharm. 2009;66:399–408.
   PubMed Web of Science ®Google Scholar
• Erlund I, Marniemi J, Hakala P, et al. Consumption of black currants, lingonberries and bilberries increases serum quercetin concentrations. Eur J Clin Nutr. 2003;57:37–42.
   PubMed Web of Science ®Google Scholar
• Matsunaga N, Tsuruma K, Shimazawa M, et al. Inhibitory actions of bilberry anthocyanidins on angiogenesis. Phytother Res. 2010;24:S42–S47.
   PubMed Web of Science ®Google Scholar
• Viljanen K, Kylli P, Kivikari R, et al. Inhibition of protein and lipid oxidation in liposomes by berry phenolics. J Agric Food Chem. 2004;52:7419–7424.
   PubMed Web of Science ®Google Scholar
• Yao Y, Vieira A. Protective activities of Vaccinium antioxidants with potential relevance to mitochondrial dysfunction and neurotoxicity. Neurotoxicology. 2007;28:93–100.
   PubMed Web of Science ®Google Scholar
• Mian E, Curri SB, Lietti A, et al. Anthocyanosides and the walls of the microvessels: further aspects of the mechanism of action of their protective effect in syndromes due to abnormal capillary fragility. Minerva Med. 1977;68:3565–3581.
   PubMed Web of Science ®Google Scholar
• Bottecchia D, Bettini V, Martino R, et al. Preliminary report on the inhibitory effect of Vaccinium myrtillus anthocyanosides on platelet aggregation and clot retraction. Fitoterapia. 1987;58:3–8.
   Google Scholar
• Harvsteen B. Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol. 1983;32:1141–1148.
   PubMed Web of Science ®Google Scholar
• Gabor M. Pharmacologic effects of flavonoids on blood vessels. Angiologica. 1972;9:355–374.
   PubMedGoogle Scholar
• Tumbasa V, Čanadanović-Brunet J, Gille L, et al. Superoxide anion radical scavenging activity of bilberry (Vaccinium myrtillus L.). J Berry Res. 2010;1:13–23.
   Google Scholar
• Valentová K, Ulrichová J, Cvak L, et al. Cytoprotective effect of a bilberry extract against oxidative damage of rat hepatocytes. Food Chem. 2007;101:912–917.
   Web of Science ®Google Scholar
• Lankinen M, Schwab U, Kolehmainen M, et al. Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial: the sysdimet study. PLoS One. 2011;6:e22646.
   PubMed Web of Science ®Google Scholar
• Lehtonen HM, Suomela JP, Tahvonen R, et al. Different berries and berry fractions have various but slightly positive effects on the associated variables of metabolic diseases on overweight and obese women. Eur J Clin Nutr. 2011;65:394–401.
   PubMed Web of Science ®Google Scholar
• Mauray A, Felgines C, Morand C, et al. Nutrigenomic analysis of the protective effects of bilberry anthocyanin-rich extract in apo E-deficient mice. Genes Nutr. 2010;5:343–353.
   PubMed Web of Science ®Google Scholar
• Mykkänen OT, Huotari A, Herzig K-H, et al. Wild blueberries (Vaccinium myrtillus) alleviate inflammation and hypertension associated with developing obesity in mice fed with a high-fat diet. PLoS One. 2014;9:e114790.
   PubMed Web of Science ®Google Scholar
• Persson IA, Persson K, Andersson RG. Effect of Vaccinium myrtillus and its polyphenols on angiotensin-converting enzyme activity in human endothelial cells. J Agric Food Chem. 2009;57:4626–4629.
   PubMed Web of Science ®Google Scholar
• Suzuki R, Tanaka M, Takanashi M, et al. Anthocyanidins-enriched bilberry extracts inhibit 3T3-L1 adipocyte differentiation via the insulin pathway. Nutr Metab. 2011;8:14.
   Google Scholar
• Takikawa M, Inoue S, Horio F, et al. Dietary anthocyanin-rich bilberry extract ameliorates hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase in diabetic mice. J Nutr. 2010;140:527–533.
   PubMed Web of Science ®Google Scholar
• Ziberna L, Lunder M, Tramer F, et al. The endothelial plasma membrane transporter bilitranslocase mediates rat aortic vasodilation induced by anthocyanins. Nutr Metab Cardiovasc Dis. 2013;23:68–74.
   PubMed Web of Science ®Google Scholar
• Marra F, Svegliati-Baroni G. Lipotoxicity and the gut-liver axis in NASH pathogenesis. J Hepatol. 2018;68:280–295.
   PubMed Web of Science ®Google Scholar
• Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313:2263–2273.
   PubMed Web of Science ®Google Scholar
• Cha J-Y, Repa JJ. The liver X receptor (LXR) and hepatic lipogenesis. The carbohydrate-response element-binding protein is a target gene of LXR. J Biol Chem. 2007;282:743–751.
   PubMed Web of Science ®Google Scholar
• Nagrath D, Xu H, Tanimura Y, et al. Metabolic preconditioning of donor organs: defatting fatty livers by normothermic perfusion ex vivo. Metab Eng. 2009;11:274–283.
   PubMed Web of Science ®Google Scholar
• Nativ NI, Yarmush G, So A, et al. Elevated sensitivity of macrosteatotic hepatocytes to hypoxia/reoxygenation stress is reversed by a novel defatting protocol. Liver Transplant. 2014;20:1000–1011.
   PubMed Web of Science ®Google Scholar
• Haga S, Min Y, Ozaki M. Relevance of FXR-p62/SQSTM1 pathway for survival and protection of mouse hepatocytes and liver, especially with steatosis. BMC Gastroenterol. 2017;17:9.
   PubMed Web of Science ®Google Scholar
• Haga S, Remington SJ, Morita N, et al. Hepatic ischemia induced immediate oxidative stress after reperfusion and determined the severity of the reperfusion-induced damage. Antioxid Redox Signal. 2009;11:2563–2572.
   PubMed Web of Science ®Google Scholar
• Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2DDCT method. Methods. 2001;25:402–408.
   PubMed Web of Science ®Google Scholar
• Dorn C, Riener MO, Kirovski G, et al. Expression of fatty acid synthase in nonalcoholic fatty liver disease. Int J Clin Exp Pathol. 2010;3:505–514.
   PubMed Web of Science ®Google Scholar
• Haga S, Ozawa T, Yamada Y, et al. p62/SQSTM1 plays a protective role in oxidative injury of steatotic liver in a mouse hepatectomy model. Antioxid Redox Signal. 2014;21:2515–2530.
   PubMed Web of Science ®Google Scholar
• Park JS, Oh SY, Lee DH, et al. p62/SQSTM1 is required for the protection against endoplasmic reticulum stress-induced apoptotic cell death. Free Radical Res. 2016;50:1408–1421.
   PubMed Web of Science ®Google Scholar
• Tanaka S, Hikita H, Tatsumi T, et al. Rubicon inhibits autophagy and accelerates hepatocyte apoptosis and lipid accumulation in nonalcoholic fatty liver disease in mice. Hepatology. 2016;64:1994–2014.
   PubMed Web of Science ®Google Scholar
• Pandey KB, Rizv SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2009;2:270–278.
   PubMed Web of Science ®Google Scholar
• Inoue H, Ogawa W, Ozaki M, et al. Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo. Nat Med. 2004;10:168–174.
   PubMed Web of Science ®Google Scholar
• De Mello VD, Schwab U, Kolehmainen M, et al. A diet high in fatty fish, bilberries and wholegrain products improves markers of endothelial function and inflammation in individuals with impaired glucose metabolism in a randomised controlled trial: the sysdimet study. Diabetologia. 2011;54:2755–2767.
   PubMed Web of Science ®Google Scholar
• Domitrović R, Jakovac H. Effects of standardized bilberry fruit extract (Mirtoselect®) on resolution of CCl4-induced liver fibrosis in mice. Food Chem Toxicol. 2011;49:848–854.
   PubMed Web of Science ®Google Scholar
• Miyake S, Takahashi N, Sasaki M, et al. Vision preservation during retinal inflammation by anthocyanin-rich bilberry extract: cellular and molecular mechanism. Lab Investig. 2012;92:102–109.
   PubMed Web of Science ®Google Scholar
• Morrison MC, Liang W, Mulder P, et al. Mirtoselect, an anthocyanin-rich bilberry extract, attenuates non-alcoholic steatohepatitis and associated fibrosis in ApoE∗ 3Leiden mice. J Hepatol. 2015;62:1180–1186.
   PubMed Web of Science ®Google Scholar