Table 1.
Publication | Berry | Population/Model | Endpoint | Method | Treatment | Effect |
---|---|---|---|---|---|---|
Lala et al., 2006 [34] (a) |
Bilberry | Fisher 344 male rats treated with azoxymethane n = 10 per group |
1. Number and multiplicity of colonic aberrant crypt foci (ACF) 2. Colonic cell proliferation |
1. Staining and light microscopy of colons 2. Proliferating cell nuclear antigen immunohistochemistry |
AIN-93 powdered diet supplemented with 3.85 g monomeric anthocyanin bilberry ARE/kg for 14 weeks | 1. Significantly reduced number of total and large ACF compared to control. Number of large ACF was reduced by 70% 2. Significantly decreased colonic cellular proliferation by nearly 50% |
Cooke et al., 2006 [9] (b) |
Bilberry | ApcMin/+ mice n = 16 per group |
Number, location, and size of adenomas in gastrointestinal tract | Dissection after termination | Standard diet with ARE from bilberry (Mirtoselect): Group 1: 0.03%, Group 2: 0.1%, Group 3: 0.3% w/w of ARE in diet for 12 weeks |
Significantly and dose-dependently reduced adenoma load compared to control (number reduced by 30% with highest dose). Reduced particularly the number of small adenomas dose-dependently in the small intestine |
Misikangas et al., 2007 [38] (b) |
Bilberry and lingonberry | C57BL/6J Min/+ mice, male and female n = 10–12 in group |
Sum of adenoma areas | Dissection after termination | 10% w/w freeze-dried bilberry or lingonberry in High-fat AIN93 diet for 10 weeks | Both berries significantly inhibited number of adenomas by 15–30% compared to control. Bilberry did not reduce the size of adenomas, but lingonberry reduced adenoma burden by 60% |
Lippert et al., 2017 [35] (a) |
Bilberry | Female Balb/c mice, Azoxymethane/dextran sodium sulphate mouse model n = 50 mice divided in 3 groups |
Tumor growth and number | Colonoscopy at weeks 4 and 9, macroscopic and microscopic analysis after termination at week 9 |
Bilberry anthocyanin-rich extract 1% or 10% w/w of extract in diet for 10 weeks |
Significantly smaller and less (almost no detectable tumors) in 10% ARE fed mice compared to controls or mice fed with 1% extract. Smaller and less tumors also with 1% extract compared to control, but difference not statistically significant |
Mudd et al., 2020 [39] (b) |
Bilberry | ApcMin/+ mice treated with antibiotics and infected with enterotoxigenic Bacteroides fragilis n = 6 per group |
Tumor number | Dissection after termination | Bilberry anthocyanin extract on average 8.6 mg/kg body weight by gavage 3 times a week for 4 weeks |
Significantly reduced tumor number approx. 50% compared to control |
Wang et al., 2020 [37] (c) |
Bilberry | Female C57BL/6 mice subcutaneously inoculated with MC38-OVA cells, receiving immune checkpoint inhibitor injections n = 6 per group |
Tumor volume | Measured every 3–4 days with an electronic caliper |
Bilberry anthocyanin extract 156 ug of anthocyanins daily for 27 days |
Extract alone did not affect tumor volume compared to control, but significantly enhanced the effect of the drug, possibly through modulation of gut microbiota (effect was abolished by antibiotic treatment) |
Liu et al., 2020 [36] (c) |
Bilberry | Female C57BL/6 mice subcutaneously inoculated with MC38-OVA cells, receiving immune checkpoint inhibitor injections n = 6 per group |
Tumor volume | Measured every 3–4 days with an electronic caliper |
Standardized bilberry ARE (Mirtoselect, Indena S.p.A. Italy) 25 mg bilberry extract/kg body weight daily for 2 weeks |
Extract was not tested alone but enhanced therapeutic effects of the drug. Enhanced tumor immune filtration was associated with improvement of tumor control. |
Animal model type used: (a) induced carcinogenesis, (b) genetic model, and (c) xenograft.