Intestinal Metabolism of Two A-type Procyanidins Using the Pig Cecum Model: Detailed Structure Elucidation of Unknown Catabolites with Fourier Transform Mass Spectrometry (FTMS)
NRW Graduate School of Chemistry, Westfälische Wilhelms-Universität Münster, Wilhelm-Klemm-Strasse 10, 48149 Münster, Germany. Journal of Agricultural and Food Chemistry
(Impact Factor: 2.91).
12/2011; 60(3):749-57. DOI: 10.1021/jf203927g
Procyanidins, as important secondary plant metabolites in fruits, berries, and beverages such as cacao and tea, are supposed to have positive health impacts, although their bioavailability is yet not clear. One important aspect for bioavailability is intestinal metabolism. The investigation of the microbial catabolism of A-type procyanidins is of great importance due to their more complex structure in comparison to B-type procyanidins. A-type procyanidins exhibit an additional ether linkage between the flavan-3-ol monomers. In this study two A-type procyanidins, procyanidin A2 and cinnamtannin B1, were incubated in the pig cecum model to mimic the degradation caused by the microbiota. Both A-type procyanidins were degraded by the microbiota. Procyanidin A2 as a dimer was degraded by about 80% and cinnamtannin B1 as a trimer by about 40% within 8 h of incubation. Hydroxylated phenolic compounds were quantified as degradation products. In addition, two yet unknown catabolites were identified, and the structures were elucidated by Fourier transform mass spectrometry.
Available from: Michael Freitag
- "In cases where only low amounts of intermediates were secreted by the mutant strains, HPLC, in combination with FTMS/MS fragmentation, was used for unequivocal structure elucidation. Previous studies of Engemann et al. could show that this is a good tool for structure elucidation (Engemann et al., 2012). As expected, Dfus1 and Dfus2-9 deletion mutants that have lost the PKS/NRPS-encoding gene fus1 or all cluster genes except for fus1, respectively, did not produce any fusarin C "
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ABSTRACT: In this work, the biosynthesis and regulation of the polyketide synthase/nonribosomal peptide synthetase (PKS/NRPS)-derived mutagenic mycotoxin fusarin C was studied in the fungus Fusarium fujikuroi. The fusarin gene cluster consists of nine genes (fus1-fus9) that are coexpressed under high-nitrogen and acidic pH conditions. Chromatin immunoprecipitation revealed a correlation between high expression and enrichment of activating H3K9-acetylation marks under inducing conditions. We provide evidence that only four genes are sufficient for the biosynthesis. The combination of genetic engineering with nuclear magnetic resonance and mass-spectrometry-based structure elucidation allowed the discovery of the putative fusarin biosynthetic pathway. Surprisingly, we indicate that PKS/NRPS releases its product with an open ring structure, probably as an alcohol. Our data indicate that 2-pyrrolidone ring closure, oxidation at C-20, and, finally, methylation at C-20 are catalyzed by Fus2, Fus8, and Fus9, respectively.
Chemistry & biology 08/2013; 20(8). DOI:10.1016/j.chembiol.2013.07.004 · 6.65 Impact Factor
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ABSTRACT: Cranberry (Vaccinium macrocarpon) products have been widely recommended in traditional American medicine for the treatment of urinary tract infection (UTI). A total of 19 different commercial cranberry products from American and European markets have been analyzed by different global phenolic methods and by UPLC-DAD-ESI-TQ MS. In addition, in vitro antioxidant capacity and uropathogenic bacterial antiadhesion activity tests have been performed. Results revealed that products found in the market widely differed in their phenolic content and distribution, including products completely devoid of flavan-3-ols to highly purified ones, either in A-type proanthocyanidins (PACs) or in anthocyanins. The product presentation form and polyphenolic profile widely affected the antiadhesion activity, ranging from a negative (nulel) effect to a MIC = 0.5 mg/mL for cranberry powders and a MIC=112 mg/mL for gel capsule samples. Only 4 of 19 products would provide the recommended dose of intake of 36 mg total PACs/day. Of most importance was the fact that this dose would actually provide as low as 0.00 and up to 205 μg/g of procyanidin A2, indicating the lack of product standardization and incongruence between global and individual compound analysis.
Journal of Agricultural and Food Chemistry 03/2012; 60(13):3396-408. DOI:10.1021/jf204912u · 2.91 Impact Factor
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ABSTRACT: Extracts from hawthorn leafs and flowers (Crataegus sp., Rosaceae) are widely used as a rational based phytomedicine for declining cardiac performance. According to present literature C-glycosylated flavones and oligomeric procyanidins are considered to be the active ingredients, despite the fact that no systematic data are available on systemic bioavailability of proanthocyanidins after oral intake. The present study aims to review the actual state of literature in this field and to investigate the intestinal absorption mechanisms of defined hawthorn PAs with different degrees of polymerization by validated in vitro Caco-2 monolayer permeation system. Hawthorn OPCs with DP 2 to 6 were isolated as defined clusters. Procyanidin B2 and the procyanidin clusters DP 4, 5 and 6 had very low P(app) values between 0.6 and 6×10⁻⁷ cm/s for apical to basolateral permeation. The higher the molecular weight the lower permeation coefficients were calculated. The observed low-level transport was mainly due to passive paracellular permeation. Additionally cellular uptake of OPCs by transcellular permeation was possible; on the other side procyanidins were shown to be p-glycoprotein substrates, which leads to subsequent excretion of PAs by the efflux pump to the apical side. Mixtures of the different OPCs did not have an increased permeation. Transport experiments of complex OPC mixtures together with hawthorn flavonoids did not indicate any improved permeation or synergistic effects. In principle this raises the question if systemic pharmacological activities of hawthorn extracts, can really be attributed to OPCs with very low systemic bioavailability.
Fitoterapia 07/2012; 83(7):1210-7. DOI:10.1016/j.fitote.2012.06.013 · 2.35 Impact Factor
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