Bifidobacterium breve MCC1274 with glycosidic activity enhances in vivo isoflavone bioavailability.

Polyphenols are plant derived compounds that exert many beneficial health effects to the human host. However, associated health benefits of dietary polyphenol are highly dependent on their intestinal metabolism, bioavailability, and absorption. Bifidobacteria, which represent the key members of gut microbiota, have been suggested to promote gut microbial homeostasis and may be involved in the metabolism of polyphenols. In this study, the capabilities of thirteen Bifidobacterium strains in hydrolysing polyphenol glycosides were evaluated. Among the tested strains, Bifidobacterium breve MCC1274 was found to possess the highest ß-glucosidase activity and strong capability to convert daidzin and trans-polydatin to their aglycones; while kinetic analysis revealed that B. breve MCC1274 hydrolysed more than 50% of daidzin and trans-polydatin at less than 3 h of incubation. Further investigation using rats with an antibiotics-disturbed microbiome revealed that following the ingestion of daidzin glycoside, oral administration of B. breve MCC1274 significantly enhanced the plasma concentration of daidzein in rats pre-treated with antibiotics as compared to antibiotics-pre-treated control and non-treated control groups. The relative abundance of Actinobacteria and the total numbers of B. breve were also significantly higher in antibiotics-pre-treated rats administered with B. breve MCC1274 than that of the control groups. These findings suggest that B. breve MCC1274 is effective in enhancing the bioavailability of daidzein in the gut under dysbiosis conditions and may potentially improve intestinal absorption of isoflavones and promote human health.

Functional chemokine receptors in allergic diseases: is CCR8 a novel therapeutic target?

CC chemokine receptor (CCR) 8, which is expressed on Th2 cells and eosinophils, has been implicated in allergic diseases. This review represents an overview of the functional roles of CCR8 in the pathogenesis of eosinophilic inflammation and debates the potential of recently developed CCR8 antagonists to treat allergic disorders.

Stereoselective synthesis of CF(2)-substituted phosphothreonine mimetics and their incorporation into peptides using newly developed deprotection procedures.

Stereoselective syntheses of all four stereoisomers of CF(2)-substituted nonhydrolyzable phosphothreonine derivatives (33, 39, and their enantiomers) and their incorporation into peptides are described herein. Key to the synthesis of these amino acids was construction of secondary phosphate-mimicking difluoromethylphosphonate units along with generation of two stereocenters. The former was achieved using a Cu(I)-mediated cross-coupling reaction of BrZnCF(2)P(O)(OEt)(2) (8) and beta-iodo-alpha,beta-unsaturated ester 12, with stereochemistry of both alpha- and beta-stereocenters being established using bornane-10,2-sultam as a chiral auxiliary. Diastereoselective hydrogenation of a chiral alpha,beta-unsaturated acylsultam (for the beta-center) (e.g., 16a) and subsequent stereoselective bromination (for the alpha-center of the threo derivative) or amination (for the alpha-center of erythro (allo) derivative) were utilized. Transesterification of the bromide to the benzyl ester followed by azide displacement of the halogen, then reduction of the resulting azide, followed by Boc-protection and finally removal of the benzyl group, afforded protected both L- and D-phosphothreonine mimetics (39 and its enantiomer). On the other hand, protected both L- and D-allo-phosphothreonine mimetics (33 and its enantiomer) were synthesized via transesterification of the above-mentioned amination product, followed by hydrogenolytic removal of the benzyl group. Key to utilization of these amino acid analogues in peptide synthesis was removal of ethyl protection from the difluoromethylphosphonate moiety. A two-step deprotection methodology, consisting of a combination of a first-step reagent [0.3 M BSTFA-TBAI in CH(2)Cl(2), BF(3).Et(2)O] followed by a second-step reagent [1 M TMSOTf-thioanisole in TFA, m-cresol, EDT] was developed for use in solid-phase protocols. A 12-residue Cdc (cell division cycle) 2-peptide 41, possessing two nonhydrolyzable phosphoamino acid mimetics (F(2)Pmab 6 and F(2)Pmp 4), was subjected to this deprotection procedure and was obtained in 25% yield based on the protected resin. The present synthetic method affords nonhydrolyzable phosphoamino acid mimetics-containing peptides in high yield without accompanying side reactions.