Flavan‐3‐ol C‐glycosides – Preparation and model experiments mimicking their human intestinal transit

Abstract

In order to study the human intestinal transit of flavan-3-ol C-glycosides, several C-glycosyl derivatives were prepared by non-enzymatic reaction of (+)-catechin with α-D-glucose, α-D-galactose and α-D-rhamnose, respectively. In contrast to literature data, we propose that the reaction mechanism proceeds in analogy to the rearrangement of flavan-3-ols during epimerization under alkaline conditions. Four of the 12 synthesized flavan-3-ol C-glycosides were incubated under aerobic conditions at 37°C using saliva (2 min) and simulated gastric juice (3 h). To simulate human intestine, the C-glycosides were also incubated under anaerobic conditions at 37°C both in human ileostomy fluid (10 h) and colostomy fluid (24 h), respectively. The flavan-3-ol C-glycosides under study, i.e. (+)-epicatechin 8-C-β-D-glucopyranoside (1a), (+)-epicatechin 6-C-β-D-glucopyranoside (1d), (+)-catechin 6-C-β-D-galactopyranoside (2b), (+)-catechin 6-C-β-D-rhamnopyranoside (3b) were analyzed in the incubation samples by HPLC-DAD and HPLC-DAD-MS/MS. They were found to be stable in the course of incubation in saliva, simulated gastric juice and ileostomy fluid and underwent degradation in colostomy fluid. While the 6-C-β-D-glucopyranoside 1d was completely metabolized between 2 and 4 h, decomposition of the 6-C-β-D-galactopyranoside 2b reached only 16 ± 2% within 4 h of incubation. Linear degradation rates of 1d and 2b in colostomy fluid differed significantly. As microbial metabolism of flavan-3-ols is known not to be influenced by the stereochemistry of the aglycon, varying degradation rates are ascribed to the effect of the sugar moiety. Based on these results we assume that flavan-3-ol C-glycosides pass through the upper gastrointestinal tract (oral cavity, stomach and small intestine) unmodified and are then metabolized by the colonic microflora.

Role of intestinal microbiota in the generation of polyphenol‐derived phenolic acid mediated attenuation of Alzheimer's disease β‐amyloid oligomerization

“…Major dietary polyphenolic components (e.g. CT and EC as well as other polyphenols, including anthocyanins , chlorogenic acid , quercetin , rutin, and naringin , can all serve as substrates for intestinal microbiota, resulting in the formation of small molecular phenolic acids. Intestinal microbiota metabolites of GSPE phenolic compounds, or PACs, have been investigated in vitro and detected in human urine .…”

The Occurrence, Fate and Biological Activities ofC-glycosyl Flavonoids in the Human Diet

“…The true significance may only be truly elucidated by employing matched aglycone and C-glycosylated standards in all investigations where practicable. This is becoming an increasingly possibility with the commercial availability of an ever-expanding range of diverse phytochemicals and the publication of a relatively simple chemical means by which aglycone polyphenols may be efficiently C-glycosylated (Hasslauer et al, 2010;Stark et al, 2007). Further pharmacokinetic studies are also required for these compounds, as limited data suggests low bioavailability, likely by virtue of the intact glycosyl group.…”

“…C-Glycosyl flavonoids survive hepatic hydrolysis for reasons outlined previously, explaining their seemingly unusual presence in human urine following oral consumption (Courts and Williamson, 2009;Hasslauer et al, 2010). As such, it is very likely that C-glycosylation does not confer diffusive flavonoid absorption per se;…”

“…Hasslauer et al (2010) examined the respective difference in the ex vivo stability of (-)-epicatechin-6-C-glucoside in buffered human ileostomy and colostomy fluids at 37°C for 10 hr (pH 6.3 and 7.4 respectively). No significant degradation occurred in ileostomy fluid, however complete degradation occurred following incubation for between 2 and 4 hr in colostomy fluid.…”

A Profile of Bioactive Compounds of Rumex vesicarius L.

“…It was proposed to be 7‐O‐rhamno‐acetylglucosyl diosmetin structure, science standards of these compounds were not available, we depend on the literature data of a compound with a near structure and defined as 7‐O‐(acetyl)‐pento‐hexosyl‐diosmetin (Ferreres and others 2006). Flavan 3‐ols in n ‐butanol fraction, according to their UV and mass spectral data, were identified as: catechin 7 , epicatechin 8 , epicatechin gallate 11, and epigallocatechin gallate 13 (Hye and others 2009; Hasslauer and others 2010; Long‐Ze and Harnly, 2010). The loss of 162 u (hexosyl radical) and 180 u (hexose + water) facilitated the identification of compound 9 and was confirmed by its UV spectra as ferulyl hexose (Ferreres and others 2006).…”