Table 3.

Prevention of disease with cranberry consumption and proposed mechanisms.

Disease Name	Proposed Mechanism	References
Urinary tract inflammation	A-type procyanidins in cranberry demonstrate anti-adhesive activity against E. coli to the uroepithelial cells preventing progression of UTIs	[34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55]
Cystitis	A-type procyanidins in cranberry prevent adhesion of E. coli to the bladder epithelial cells preventing progression of UTIs	[56,57,58,59,60,61,62]
Oxidative stress	Polyphenols in cranberry alleviate intestinal oxidative stress and inflammation while improving mitochondrial dysfunction by quenching reactive oxygen species.	[63,64,65]
Cardiovascular	Polyphenols in cranberry may reduce the risk of cardiovascular disease by increasing the LDL resistance to oxidation, hindering platelet accumulation, decreasing blood pressure.	[66,67,68,69,70,71,72]
Obesity	Lyophilized cranberries reduced fat accumulation during preadipocyte differentiation by decreasing the number of receptors on the surface of target cells of the mRNA level of adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), hormone sensitive lipase (HSL) and perilipin 1 (PLIN1). Therefore, cranberries are effective in preventing the production of adipose tissue.	[73]
Type 2 diabetes	Cranberries improved post-prandial glucose concentration due to high fat and inflammation and oxidation in diabetic individuals.	[74]
Helicobacter pylori suppression	Non-dialyzable substances from cranberry obstruct the sialic acid-specific adhesion of H. pylori to human gastric mucus and to erythrocytes.	[75,76,77,78,79,80]
Cancers	Prostate-Cranberry PACs reduced matrix metalloproteinases (MMP) activity in prostate cancer cells via stimulating and hindering specific MMP regulators, and by disrupting either the phosphorylation status and/or expression of MAP kinase, PI-3 kinase, and NF-κB and AP-1 pathway proteins. Bladder-Isorhamnetin and quercetin 3-O-glucoside, the active forms of quercetin may be responsible in prevention of bladder cancer in vivo and diets high in cranberries for the prevention of bladder carcinoma. Breast-Cranberry phytochemical may potentially suppress the spread of human breast cancer MCF-7 cells, which is partly due to both the beginning of apoptosis and the G1 phase arrest. Lung-PACs in cranberry can modify gene expression, stimulate apoptosis and induce the cell cycle of human NCI-H460 lung cancer cells.	[81,82,83]
Rheumatoid arthritis	Quercetin, a flavonoid present in cranberry, is a powerful suppressor of the nuclear factor (NF)-ĸB-pathway. It also impedes the activities of cyclooxygenase and lipoxygenase, enzymes released after the stimulation of arachidonic acid, which is the initiator of an inflammatory response. Resveratrol, a polyphenol in cranberry, also has been shown to reduce inflammatory genes expression important for cardiovascular disease by regulating the NF-ĸB and JAK STAT3 pathways in cells.	[84]
Tooth decay and periodontitis	Polyphenols in cranberry serve as dental anticaries agents by impeding the production of organic acids and the formation of biofilms by cariogenic bacteria. Additionally, they may reduce inflammation as well as the production and activity of proteolytic enzymes destroying the extracellular matrix in periodontal disease. These polyphenols also interfere with other activities such as formation of biofilm and adhesion of Porphyromonas gingivalis, the main disease-causing agent in chronic periodontitis.	[85,86,87,88]
Infectious	PAC in cranberries block adhesion to and biofilm formation on target tissues of pathogens	[89]
Kidney	Cranberries enriched with PACs can alleviate the complications associated with chronic kidney disease such as oxidative stress, inflammation and gut dysbiosis	[90]
Intestinal microbiota	The rich cranberry content of polyphenols, phenolic acids, isoprenoids and oligosaccharides performing in the gastrointestinal tract may reduce reactive oxygen species, control pathways of inflammation, attach to carbohydrates and proteins on surfaces of bacteria, employ prebiotic effects, and change the transmission of signals between intestinal epithelial cells and the gut microbiota.	[91]
Flu virus	High molecular weight substances (NDM) in cranberry inhibited Influenza virus A subtypes (H1N1 and H3N2) and the B type, which was shown by the cytopathic effect on Madine-Darby canine kidney (MDCK) cells and the lack of hemagglutination of red blood cells activity in infected cells.	[92,93]
Microbial	Cranberry phenolic extracts impeded the growth of human pathogenic bacteria: Escherichia coli, Salmonella typhimurium, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, and Bacillus subtilis in different mechanisms.	[94,95,96,97]