Phenyl-γ-valerolactones and phenylvaleric acids, the main colonic metabolites of flavan-3-ols: synthesis, analysis, bioavailability, and bioactivity

Abstract

This review focuses on several key aspects related to the main group of phenolic metabolites in circulation.

Flavonoid‐Derived Human Phenyl‐γ‐Valerolactone Metabolites Selectively Detoxify Amyloid‐β Oligomers and Prevent Memory Impairment in a Mouse Model of Alzheimer's Disease

“…Based on a cross‐species exploration focused on β‐amyloid oligomer‐induced cytotoxicity, this work documents the anti‐AβO action of the PVL metabolites of flavan‐3‐ols, the major class of flavonoids in the human diet …”

“…This largely unsatisfactory outlook has spurred great interest in various natural compounds, especially polyphenols, that in various experimental settings have proven capable of modifying different neuropathological features of AD and to promote Aβ peptide detoxification by either interfering with AβO formation and/or by inducing the conversion of pre‐existing AβOs into nontoxic higher‐order aggregates . Special attention, in this context, has been given to flavan‐3‐ols, polycyclic flavonoids that are particularly abundant in cocoa, tea, berries, red wine, and other plant‐derived foods and beverages . Much less investigated, instead, have been the human metabolites of flavan‐3‐ols, only a few of which have been shown to mitigate Aβ (including AβO) toxicity …”

“…Phenyl‐γ‐valerolactones (PVL) are the major group of circulating flavan‐3‐ol metabolites in humans . As outlined in Figure 1, PVLs can originate from (−)‐epicatechin but also from condensed epicatechins such as the dimeric procyanidin B2, through 5‐carbon side‐chain ring fission catalyzed by gut, mainly colonic, microbial enzymes, and subsequent phase II metabolic conversion by host hepatic enzymes .…”

“…Phenyl‐γ‐valerolactones (PVL) are the major group of circulating flavan‐3‐ol metabolites in humans . As outlined in Figure 1, PVLs can originate from (−)‐epicatechin but also from condensed epicatechins such as the dimeric procyanidin B2, through 5‐carbon side‐chain ring fission catalyzed by gut, mainly colonic, microbial enzymes, and subsequent phase II metabolic conversion by host hepatic enzymes . According to recent metabolic profiling studies in humans, ≈42% of ingested (−)‐epicatechin is converted within 4 to 12 h into PVLs, which reached peak plasma levels within 6 h and were still well detectable after 24 h .…”

“…According to recent metabolic profiling studies in humans, ≈42% of ingested (−)‐epicatechin is converted within 4 to 12 h into PVLs, which reached peak plasma levels within 6 h and were still well detectable after 24 h . These data highlight the need to consider PVLs as potential AβO targeting compounds responsible for, or at least contributing to, the anti‐neurodegenerative effects of dietary flavan‐3‐ols …”