5-(3′,4′-Dihydroxyphenyl)-γ-valerolactone and its sulphate conjugates, representative circulating metabolites of flavan-3-ols, exhibit anti-adhesive activity against uropathogenic Escherichia coli in bladder epithelial cells

Urinary tract infections (UTI) are mostly caused by uropathogenic Escherichia coli (UPEC). Cranberry-based products have shown preventive effects against UTI, and this has been partially attributed to their A-type proanthocyanidin content. However, recent evidence reports phenyl-γ-valerolactones as the most relevant urinary metabolites of cranberry procyanidins, and candidates these compounds as plausible responsible for the protective effects of cranberries against UTI. This paper studied the inhibition of the adherence of UPEC ATCC®53503™ to T24 bladder epithelial cells by physiological concentrations of differently sulphated dihydroxyphenyl-γ-valerolactones. Moreover, the transformations of these molecules in the cell media were evaluated by UHPLC-MSn. All dihydroxyphenyl-γ-valerolactone derivatives showed anti-adhesive activity at 100 μM, while 5-(3′-hydroxyphenyl)-γ-valerolactone-4-O-sulphate also showed neuro-protective effects at 50 μM. Some compounds underwent extensive metabolism during cell incubation, mainly deconjugation of sulphate moieties and opening of the lactone ring. These results shed light on the flavan-3-ol metabolites behind the prophylactic effect of cranberries against UTI.