Membrane organic anion-transporting polypeptides (OATPs) are responsible for the drug transmembrane transport within the human body. The function of OATP2B1 transporter can be inhibited by various natural compounds. Despite increased research interest in soya as a part of human diet, the effect of its active components to interact with hOATP2B1 has not been elucidated in a complex extent. This in vitro study examined the inhibitory effect of main soy isoflavones (daidzin, daidzein, genistin, genistein, glycitin, glycitein, biochanin A, formononetin) and their metabolites formed in vivo (S-equol, O-desmethylangolensin) towards human OATP2B1 transporter. MDCKII cells overexpressing hOATP2B1 were employed to determine quantitative inhibitory parameters of the tested compounds and to analyze mechanism/s of the inhibitory interaction. The study showed that aglycones of soy isoflavones and the main biologically active metabolite S-equol were able to significantly inhibit hOATP2B1-mediated transport. The Ki values for most of aglycones range from 1 to 20 μM. In contrast, glucosides did not exhibit significant inhibitory effect. The kinetic analysis did not indicate a uniform type of inhibition towards the hOATP2B1 although predominant mechanism of inhibition seemed to be competitive. These findings may suggest that tested soy isoflavones and their metabolites might affect transport of xenobiotics including drugs across tissue barriers via hOATP2B1.

• Klíčová slova
• Drug transporter, Flavonoids, OATP, SLCO, Soy isoflavones,
• MeSH
• buňky MDCK MeSH
• Glycine max * MeSH
• isoflavony farmakologie   MeSH
• kinetika MeSH
• přenašeče organických aniontů antagonisté a inhibitory   genetika   metabolismus   MeSH
• psi MeSH
• transfekce MeSH
• zvířata MeSH
• Check Tag
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• isoflavony MeSH
• přenašeče organických aniontů MeSH
• SLCO2B1 protein, human MeSH Prohlížeč

In this study, we compared the effects of two diets containing different isoflavone concentrations on the isoflavone transfer from feed into milk and on the rumen microbiota in lactating dairy cows. The on-farm experiment was conducted on twelve lactating Czech Fleckvieh x Holstein cows divided into two groups, each with similar mean milk yield. Twice daily, cows were individually fed a diet based on maize silage, meadow hay and supplemental mixture. Control group (CTRL) received the basal diet while the experimental group (EXP) received the basal diet supplemented with 40% soybean isoflavone extract. The average daily isoflavone intake in the EXP group (16 g/day) was twice as high as that in the CTRL group (8.4 g/day, P<0.001). Total isoflavone concentrations in milk from the CTRL and EXP groups were 96.89 and 276.07 μg/L, respectively (P<0.001). Equol concentrations in milk increased from 77.78 μg/L in the CTRL group to 186.30 μg/L in the EXP group (P<0.001). The V3-4 region of bacterial 16S rRNA genes was used for metagenomic analysis of the rumen microbiome. The experimental cows exhibited fewer OTUs at a distance level of 0.03 compared to control cows (P<0.05) and reduced microbial richness compared to control cows based on the calculated Inverse Simpson and Shannon indices. Non-metric multidimensional scaling analysis showed that the major contributor to separation between the experimental and control groups were changes in the representation of bacteria belonging to the phyla Bacteroidetes, Proteobacteria, Firmicutes, and Planctomycetes. Surprisingly, a statistically significant positive correlation was found only between isoflavones and the phyla Burkholderiales (r = 0.65, P<0.05) and unclassified Betaproteobacteria (r = 0.58, P<0.05). Previous mouse and human studies of isoflavone effects on the composition of gastrointestinal microbial populations generally report similar findings.

• MeSH
• bachor mikrobiologie   MeSH
• Bacteria klasifikace   genetika   izolace a purifikace   MeSH
• Bacteroidetes genetika   izolace a purifikace   MeSH
• Betaproteobacteria genetika   izolace a purifikace   MeSH
• Burkholderiaceae genetika   izolace a purifikace   MeSH
• dieta veterinární   MeSH
• Firmicutes genetika   izolace a purifikace   MeSH
• fyziologie výživy zvířat účinky léků   MeSH
• Glycine max metabolismus   MeSH
• isoflavony farmakologie   MeSH
• krmivo pro zvířata analýza   MeSH
• kukuřice setá MeSH
• laktace MeSH
• lipnicovité MeSH
• mikrobiota MeSH
• mléko chemie   MeSH
• Planctomycetales genetika   izolace a purifikace   MeSH
• potravní doplňky * MeSH
• RNA ribozomální 16S genetika   MeSH
• rostlinné extrakty MeSH
• siláž MeSH
• skot MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• isoflavony MeSH
• RNA ribozomální 16S MeSH
• rostlinné extrakty MeSH