In vitro, bilberry polyphenols inhibited amyloid fibril formation and dissolved preformed toxic aggregates and mature fibrils, suggesting a role in controlling fibril formations of various proteins that occur with neurodegenerative diseases (1). Bilberry anthocyanins modulated oxidative stress defense enzymes heme oxygenase-1 (HO-1) and glutathione S-transferase-pi (GST-pi) in human retinal pigment epithelial cells (2). In vitro and in vivo, bilberry inhibited angiogenesis through inhibition of ERK 1/2 and Akt phosphorylation (4). In an animal model of uveitis and retinal inflammation, pretreatment with bilberry extract prevented photoreceptor impairment, relieved intracellular ROS elevation, activated retinal NF-ĸB in the inflamed retina, and suppressed the decrease of rhodopsin via inhibition of IL-6, which activates STAT3, thereby protecting outer segment length in photoreceptor cells (3). In a monocytic cell line, quercetin, epicatechin, and resveratrol inhibited lipopolysaccharide (LPS)-induced NF-kappaB activation (14).
In individuals with hypercholesterolemia, anthocyanins may improve endothelium-dependent vasodilation by activating the NO-cGMP signaling pathway (28). The polyphenols in bilberry juice can modulate inflammation by decreasing plasma C-reactive protein, interleukin (IL)-6, -15, and monokine induced by INFγ (MIG) (14).
In human colon and liver cancer cell lines, bilberry anthocyanins demonstrated intracellular antioxidant activity even though concentrations applied were very low (29). Bilberry extract can inhibit human leukemia, colon, and breast cancer cells through apoptotic induction and/or inhibition of cell proliferation (17) (30). Delphinidin and other isolated anthocyanidins synergistically enhanced cell-cycle arrest and apoptotic induction in aggressive non-small-cell lung cancer cell lines by modulating Notch, WNT, and NF-ĸB signaling pathways (16). Their malfunction in cancers fuel cell regeneration and chemotherapy-resistance, and delphinidin particularly appeared to be the most effective at Notch1 and NF-ĸB inhibition (16).