First-Pass Metabolism of Polyphenols from Selected Berries: A High-Throughput Bioanalytical Approach

Abstract

Small berries are rich in polyphenols whose first-pass metabolism may alter their ultimate physiological effects. The antioxidant capacity and polyphenol profile of three freeze-dried berries (blackberry, raspberry, Red Globe grape) were measured and their apparent permeability (Papp) and first-pass biotransformation were tracked with an ex vivo bioanalytical system [everted gut sac (rat) + three detection methods: spectrophotometry, HPLC-ESI-QTOF-MS, differential pulse voltammetry (DPV)]. Total polyphenol (ratio 0.07-0.14-1.0) and molecular diversity (anthocyanins > flavan-3-ols), antioxidant capacity (DPPH, FRAP), anodic current maxima and Papp (efflux> uptake) were in the following order: blackberry > raspberry > Red Globe grape. Epicatechin, pelargonidin & cyanin (all), callistephin (raspberry/blackberry), catechin (grape), cyanidin glycosides (blackberry) and their derived metabolites [quinic acid, epicatechin, cyanidin/malvidin glucosides, and chlorogenic/caffeic acids] were fruit-specific and concentration-dependent. Time-trend DPV kinetic data revealed concurrent epithelial permeability & biotransformation processes. Regular permeability and high-biotransformation of berry polyphenols suggest fruit-specific health effects apparently at the intestinal level.

In vitrogastrointestinal digestion impact on stability, bioaccessibility and antioxidant activity of polyphenols from wild and commercial blackberries (Rubusspp.)

“…9,56 Frequently, anthocyanins are the first compounds that come into contact with the hostile environment of the mouth during mastication, which is when the metabolism of plant pigments begins. 9,57,58 The physicochemical conditions in the oral cavity ( pH, electrolytes, temperature, darkness, decreasing O 2 content, enzymes, etc.) have a negative influence on anthocyanin stability, usually resulting in anthocyanin degradation.…”

“…6,9,57,58,[60][61][62] Since anthocyanins have low bioavailability after GID, the above-mentioned phenolic acids plus p-coumaric acid (one of the simplest metabolites of anthocyanins and other phenolic compounds produced during GID) are considered to be bioavailable and bioactive remnants of anthocyanins in the human body. 58,63 About 12 flavanols and proanthocyanidins found in the WB and CB samples are listed in Table 2. While the catechin content of WB fruits, initially 48.52 μg mL −1 and completely degraded after GID, while it remained at 5.32 μg mL −1 in CB after GID (BI of 14%).…”

“…Caffeic acid is a hydroxycinnamic acid, the main metabolites of which are vanillic acid isomers, which could be produced by spontaneous cleavage of protocatechuic acid. 47,58 The metabolism of this phenolic compound could contribute to the increase in vanillic acid isoforms. In the Andean berry, the caffeic acid content decreased by 74% after the IP 70 (a bigger decrease than in CB digestates, but smaller than in WB samples).…”

“…p-Coumaric acid, a hydroxycinnamic acid, is found in blackberry fruits in moderate concentrations, but its content increases with the metabolism of cyanidin anthocyanins during GID, for example, via dehydration of caffeic acid and/or decarboxylation of ferulic and neochlorogenic acids. 6,58,60,74 In blueberry fruits, Gapski et al 73 observed that this phenolic compound was not reported after in vivo GID. It has been found in the bloodstream after berry consumption, which may be due to the metabolism of free phenolic acids, such as caffeic or ferulic acids, or degradation of flavonoids, including cyanidin and quercetin derivatives.…”

“…During digestion, phenolics are metabolized and they can exhibit bioactivity while interacting with the gut epithelial surface. 58 The CAA assay evaluates the ability of an antioxidant to interrupt the reaction between ROO• (generated by AAPH) and a target probe. 35 It has gained importance in recent years because it provides more relevant information on antioxidant mechanisms in experimental cells lines than in in vitro (chemical) AOX assays.…”