BIOACCESIBILITY, FIRST-PASS BIO-TRANSFORMATION AND CYTOTOXICITY OF PHENOLIC COMPOUNDS FROM SELECTED SMALL FRUITS

Abstract

Introduction: Small fruits are good sources of phenolic compounds but their ultimate bio availability and biological action depends on their enteral bio accessibility and first-pass metabolism. Objective: To evaluate the antioxidant profile, first-pass metabolism and anti-proliferative capacity of three fruits with graded levels of phenolic compounds Methodology: Phenolic compounds (PC) and antioxidant capacity of globe grape, raspberry and blackberry was evaluated by spectrophotometry and HPLC-ESI-q-TOF-MS. In vitro bioaccesibility of PC subclasses was followed under simulated GI conditions (oral, gastric, intestinal). Real-time ex vivo (gut everted sac) monitoring of first-pass phenolic metabolites and PC’s apparent permeability (Papp) were followed by differential pulse voltammetry (0 to 120 min), spectrophotometry and HPLC-ESI-q-TOFMS (120 min). The anti-proliferative capacity of main PC and metabolites was assayed (MTT). Main findings: PC richness/fingerprint (cyanidin/pelargodin derivates, catechin, epicatechin), antioxidant (DPPH, FRAP) and electrochemical reactivity and bioaccesibility (total PC and flavonoids) was red blackberry> raspberry> globe grape. In vitro anthocyanins’ stability was pH-dependent. Papp of PC from globe grape favored their absorption while PC efflux was favored in raspberry and blackberry. PC’s absorption and ex vivo biotransformation was fruit-dependent and quinic acid (raspberry/blackberry), malvidin-3-O-glucoside and caffeic acid (blackberry) were major metabolites but they did not showed antiproliferative capacity in normal retinal, breast, lung and colorectal carcinoma cells. Conclusion: PC’s bioaccesibility, chemical stability, first-pass metabolism was fruit richness-dependent but the anti-cancer potential of its metabolites (bioequivalence) is not.

Mexican Council of Science and Technology (CONACyT; project CB-2015-1/254063)

Key words: Phenolic compounds, bioaccesibility, first-pass metabolism, MTT assay