Table 1.
Anti-inflammatory effects of bilberry extracts in cell and animal models.
| Ref. | Treatment | Model | Effects |
|---|---|---|---|
| [46] | Pretreatment with bilberry (40% anthocyanins), 75 µg/mL, 30 min + 40 ng/mL LPS for 6 h | RAW264.7 | ↓TNF-α, ↓IL-1β, ↓IL-6, ↓TNC, ↓PTGS2, ↓COX-2, ↓CCL22, ↓IFI47, and ↓IFI1 |
| [51] | H2O2 (200 μM) + bilberry extract (1, 10, 100 and 200 μg/mL), 24 h | RAW264.7 | ↓COX2, ↓IL-1β, ↑NFE2L2, ↓NF-κB1, ↓NF-κB2, ↓TNFα, inhibited NOS2 |
| [52] | LPS (1 μg/mL) with hydroethanolic extracts (400, 800 μg/mL), 24 h | RAW 264.7 | No cytotoxicity, ↓NO, ↓COX-2, ↓iNOS, ↓IL-6 and ↓TNF-α. IC50 (μg/mL) = DPPH (151.98 ± 1.41), ABTS (57.15 ± 0.95) |
| [54] | Bilberry extract 20 min prior to TNF-α or IFN-γ (100 ng/mL each) | THP-1 | ↓p-STAT1, ↓p-STAT3, ↓MCP-1, ↓IL-6, ↓TNF-α, ↓ICAM-1, ↓T-bet (transcription factor) |
| [56] | Carrageenan (450 μg/paw) 50 and 200 mg/kg, 10 days |
Mice | Paw edema reduction at low dose = 35.4% and high dose = 28.8% |
| [57] | Extract concentration 0.01% to 3%, 2 h followed by LPS (25 ng/mL), 8 h HeLa-TLR4, THP-1 (50 ng/mL, 4 h), HEKTLR2/HEK-TLR4 (100 ng/mL overnight incubation) | THP-1, HeLa-TLR4, HEKTLR2/HEK-TLR4 | ↑ cell viability, anti-inflammatory effects |
| [58] | LPS (0.5 mg/kg)-induced liver damage. 50, 100 and 200 mg/kg/day, 7 days |
Kunming mice | ↓plasma ALT and AST, ↓histopathogical injury, ↓TNF-α, ↓IL-1β, ↓IL-6, ↓iNOS, ↓NO, ↓NF-κB1, ↓ MDA in the liver |
| [60] | Pretreatment of bilberry−50, 100, 200 mg/kg/day, 5 days + LPS (100 mg/mouse), 24 h |
BALB/C mice | ↑ORAC, ↑GSH, ↑vitamin C, ↑SOD ↑GPx, ↓MDA |
| [61] | Acute colitis (2.5% DSS, 7 days), chronic colitis (2.5% DSS, 4 cycles for 7 days interrupted by 7 days). Feed + 20% dried bilberries (10% AC extract) | BALB/C mice | Preserved normal colon length ↓IFN-γ, ↓TNF-α, ↓IL−6 |
| [62] | IFN-γ (10 ng/mL), IL-1β (5 ng/mL), TNF-α (10 ng/mL), 4 or 16 h. Anthocyanins (25−300 μM, 4 h) or BE (10−500 μg/mL, 24 h) | T84 | ↓TNF-α, ↓IP-10, ↓I-TAC, ↓sICAM-1, ↓GRO-α |
| [64] | HFD + 5% or 10% (w/w) of whole bilberries (BB), 24 weeks | C57BL/6J mice | ↓Weight gain, ↓Th1 cells |
| [65] | HF diet. Bilberry anthocyanins dose: 0.1% w/w (35% ACY), 24 weeks | C57BL/6J mice | ↓TNF-α |
| [66] | Anthocyanin rich grape and bilberry juice, 1551 mg ACY/L (15 mg ACY per day), 10 weeks |
Fischer rats | ↓serum cholesterol, ↓TG, ↓leptin, ↓resistin No changes in adiponectin, secretion of adipokines from adipose tissue |
ABTS: 2, 2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid); ALT: alanine aminotransferase; AST: aspartate transaminase; CCL22, CC chemokine ligand 22; COX-2: cyclooxygenase-2; DPPH: 2,2-Diphenyl-1-picrylhydrazyl; DSS: dextrane sodium sulphate; GPx: glutathione peroxidase; GRO-α: growth-related oncogene-alpha; GSH: glutathione; H2O2: hydrogen peroxide; HFD: high-fat diet; I-TAC: interferon-inducible T cell alpha chemoattractant; IC50: half-maximal inhibitory concentration; IFI, interferon-inducible protein; IL: interleukin; iNOS: inducible nitric oxide synthase; IP-10: interferon gamma-induced protein 10; LPS: lipopolysaccharide; MCP-1: monocyte chemoattractant protein-1; MDA: malondialdehyde; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; NFE2L2: NFE2 Like BZIP transcription factor 2; NO: nitric oxide; NOS2: nitric oxide synthase 2; ORAC: oxygen radical absorbance capacity; p-STAT: phosphorylated signal transducer and activator of transcription; PTGS2: prostaglandin-endoperoxide synthase 2; sICAM-1: soluble intercellular adhesion molecule-1; SOD: superoxide dismutase; TG: triglyceride; TLR: Toll-like receptor; TNC: tenascin; TNF-α: tumor necrosis factor-alpha. ↑: increased; ↓: decreased.