Elsevier

Phytochemistry

Volume 66, Issue 18, September 2005, Pages 2281-2291
Phytochemistry

A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity

https://doi.org/10.1016/j.phytochem.2005.05.022Get rights and content

Abstract

Clinical, epidemiological and mechanistic studies support the role of cranberry (Vaccinium macrocarpon Ait.) in maintaining urinary tract health. Cranberry proanthocyanidins contain A-type linkages and have been associated with preventing adhesion of P-fimbriated uropathogenic Escherichia coli to uroepithelial cells. It is not known if the presence of the A-type linkage is a prerequisite for anti-adhesion activity. Other commercial sources of proanthocyanidins with all B-type linkages have not previously been screened for this activity. The goals of this study were to compare the in vitro anti-adhesion activity of A-linked proanthocyanidins from cranberry juice cocktail with the anti-adhesion activities of B-linked proanthocyanidins from commercial grape and apple juices, green tea and dark chocolate, and determine if anti-adhesion activity is detectable in human urine following consumption of single servings of each commercial food product. Structural heterogeneity and presence of the A-type linkage in cranberry proanthocyanidins was confirmed utilizing MALDI-TOF/MS and DI/ESI MS, as was the presence of all B-type linkages in the proanthocyanidins from the other commercial products. The isolated A-type proanthocyanidins from cranberry juice cocktail elicited in vitro anti-adhesion activity at 60 μg/ml, the B-type proanthocyanidins from grape exhibited minor activity at 1200 μg/ml, while other B-type proanthocyanidins were not active. Anti-adhesion activity in human urine was detected following cranberry juice cocktail consumption, but not after consumption of the non-cranberry food products. Results suggest that presence of the A-type linkage in cranberry proanthocyanidins may enhance both in vitro and urinary bacterial anti-adhesion activities and aid in maintaining urinary tract health.

Graphical abstract

Cranberry juice cocktail containing A-type proanthocyanidins exhibited bacterial anti-adhesion activity in human urine when compared to foods containing B-type proanthocyanidins. Proanthocyanidin linkage type and differences among general structural features may be contributing to anti-adhesion activity.

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Introduction

Clinical evidence supports the role of cranberry in the prevention of urinary tract infections (UTIs) (Avorn et al., 1994, Walker et al., 1997, Kontiokari et al., 2001, Stothers, 2002). Adhesion of bacteria to the uroepithelium is the initial step in development of mammalian UTI. Cranberry may act by inhibiting the adhesion of P-fimbriated uropathogenic strains of Escherichia coli to uroepithelial cells (Sobota, 1984, Zafriri et al., 1989, Ofek et al., 1991). E. coli strains that express P-fimbriae are associated with both cystitis and pyelonephritis (Roberts et al., 1989). The majority of P-fimbriated E. coli that cause UTIs bind glycosphingolipid receptor sites (i.e., α-Gal(1  4)β-Gal disaccharide) on the uroepithelium that are similar in structure to the P blood group antigens on the surface of A1, Rh+ human red blood cells (HRBCs) (Kallenius et al., 1980, Leffler and Svanborg-Eden, 1980).

Howell et al. (1998) determined that proanthocyanidins isolated from cranberry fruit inhibited P-fimbrial adhesion in vitro, and thus may be the compounds responsible for the beneficial effect on UTI prevention. Mice fed isolated cranberry proanthocyanidins in their drinking water exhibited bacterial anti-adherence activity in their urine (Howell et al., 2001). Howell and Foxman (2002) found that the urine of humans that consumed cranberry juice cocktail exhibited anti-adhesion activity. This suggests that a certain level of absorption occurred and that bioactive proanthocyanidins and/or their metabolites may have been excreted in the urine to inhibit adhesion. Larger proanthocyanidin oligomers may undergo some degradation by colonic microflora and further biotransformation forming sulphate ester or glucoronide-conjugated metabolites (Harmand and Blanquet, 1978).

Cranberry proanthocyanidins have unusual A-type linkages (Foo et al., 2000a, Foo et al., 2000b) compared to the more common B-type linkages found in proanthocyanidins from other tannin-rich foods. No data exist on the anti-adhesion activity of B-linked proanthocyanidins. It is important to determine if molecular linkage type is associated with anti-adhesion activity. If the A-type linkage was found to be prerequisite for anti-adhesion activity, especially in urine, it could help to explain why cranberry consumption prevents UTIs and other foods containing all B-linked proanthocyanidin do not. The purpose of this study was to compare the in vitro anti-adhesion activity of cranberry juice cocktail with those of several non-cranberry food products containing proanthocyanidins with B-type linkages and attempt to detect anti-adhesion activity in human urine following consumption of these products. Confirmation of proanthocyanidin linkage type and structural complexities in commerical food products requires sophisticated analytical techniques. Mass spectrometry that uses “soft” ionization techniques such as matrix assisted laser desorption ionization (MALDI-TOF MS) or electrospray ionization (DI/ESI MS) is capable of elucidating presence of A- or B-type linkages (Foo et al., 2000a, Porter et al., 2001, Krueger et al., 2000b, Krueger et al., 2003, Krueger et al., 2004). To associate linkage type with anti-adhesion activity, extracts enriched for proanthocyanidins were isolated from cranberry juice cocktail and other commercial food products and general structural heterogeneities and linkage types determined utilizing MALDI-TOF MS and DI/ESI MS.

Section snippets

Urinary bacterial anti-adhesion activity following product consumption

Bacterial anti-adhesion activity was detectable only in the urines of those volunteers that consumed a single serving (240 ml) of the cranberry juice cocktail (Fig. 1). This 240-ml dose contained the equivalent of 83 mg of proanthocyanidin with at least one A-type linkage. Detection of the activity continuously increased in a regular progression, peaking at 4–6 h post-consumption and persisting in the urine for at least 8 h, suggesting potential protection against bacterial attachment in the

Conclusions

It was not our intent to perform structural elucidation of proanthocyanidins in this study, but rather attempt to associate the A-type linkage in cranberry proanthocyanidins with greater bacterial anti-adhesion activity than that expressed by proanthocyanidins with B-type linkages. The spectrometry techniques were used to confirm the presence of the A- or B-type linkages and ascertain any unusual structural features of the molecules that could help explain the differences in biological

Proanthocyanidin-containing foods

Four different juice products and one chocolate product were purchased from the local supermarket. A portion of each product sample was used for human consumption to detect anti-adhesion activity in urine and the remainder was used to extract the proanthocyanidins for structural feature studies. The same manufacturing code (lot) of each sample was used for both the proanthocyanidin fractions and the urine activity studies. Products tested included: (1) Ocean Spray Cranberry Juice Cocktail (27%

Acknowledgements

We would like to thank Ocean Spray Cranberries, Inc. for partially supporting this research.

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