Innovative bioguided fractionation of cranberry juice for Candida biofilm treatment and infected-wound healing

Abstract

Cranberry polyphenols are intensively studied for their anti-infectious and antioxidant properties. Nevertheless, in biofilm and infected-wound healing, the identity of active polyphenols still remains unclear. In order to identify active polyphenols, an innovative fractionation scheme based on Centrifugal Partition Chromatography (CPC) was developed. CPC is a support free liquid/liquid chromatographic technology used here for the first time to fractionate cranberry juice. The fractionation protocol involved 3 mains steps: firstly polyphenol and sugars separation; then polyphenols fractionation based of molecular weight and polarity, and finally CPC or on LH-20 resin.Following the second step, the 6 main fractions obtained were screened on Candida biofilm and toward infected wound. Fractions containing low molecular weight proanthocyanidins (Fr Ill and IV) and containing high molecular weight PAC (Fr V ad VI) exhibited the most interesting activities. Concerning Candida albicans biofilm a prophylactic effect was observed by prevention of adhesion. On infected wound, a wound-healing potential related to anti-inflammatory effect but not to antibacterial activity against Staphylococcus aureus was highlighted.These four active fractions were further purified using either CPC or LH-20 resin, to lead to almost 40 sub-fractions.Against fractions containing PACs of medium and high molecular weight exhibited the highest activity against adhesion step of C. albicans strains and infected wound healing.This work is a step further to understand mechanisms of action of cranberry polyphenols on C. albicans biofilm prevention and in infected wound healing