3-4-dihydroxyphenylpropionic-acid and dihydroferulic-acid

Cardiovascular disease (CVD) is the major cause of morbidity and mortality worldwide. The consumption of a healthy diet rich in polyphenols has been inversely associated with the development of CVD. This study evaluated the effects of green coffee bean extract (GCBE) and yerba mate phenolic extract (YMPE), the main phenolic and methylxanthine constituents (5-caffeoylquinic acid, 3,5-dicaffeoylquinic acid, caffeine, and theobromine), and their main metabolites (caffeic acid, ferulic acid, dihydrocaffeic acid (DHCA) and dihydroferulic acid (DHFA)) on platelet activation in vitro. Upon incubation with different doses (0.01-100 μg mL

Topics: Adult; Aged; Blood Platelets; Caffeic Acids; Coffea; Colon; Coumaric Acids; Female; Humans; Male; Middle Aged; P-Selectin; Phenols; Plant Extracts; Platelet Activation; Young Adult

Avenanthramides (AVAs), which are found exclusively in oats, may play an important role in anti-inflammation and antiatherogenesis. Although the bioavailability of AVAs has been investigated previously, little is known about their metabolism.. The aim of the present study was to investigate the metabolism of avenanthramide-C (2c), one of the major AVAs, in mice and by the human microbiota, as well as to elucidate the bioactivity of its major metabolites with the goal of finding new exposure markers to precisely reflect oat consumption.. For the mouse study, 10 CF-1 female mice were divided into control (vehicle-treated) and 2c intragastrically treated (200 mg/kg) groups (5 mice/group). Twenty-four-hour urine and fecal samples were collected with use of metabolic cages. For the batch culture incubations, 2c was cultured with fecal slurries obtained from 6 human donors. Incubated samples were collected at various time points (0, 12, 24, 48, 72, 96, and 120 h). Metabolites were identified via HPLC with electrochemical detection and LC with electrospray ionization/mass spectrometry. To investigate whether 2c metabolites retain the biological effects of 2c, we compared their effects on the growth of and induction of apoptosis in HCT-116 human colon cancer cells.. Eight metabolites were detected from the 2c-treated mouse urine samples. They were identified as 5-hydroxyanthranilic acid (M1), dihydrocaffeic acid (M2), caffeic acid (M3), dihydroferulic acid (M4), ferulic acid (M5), dihydroavenanthramide-C (M6), dihydroavenanthramide-B (M7), and avenanthramide-B (M8) via analysis of their MS(n) (n = 1-3) spectra. We found that the reduction of 2c's C7'-C8' double bond and the cleavage of its amide bond were the major metabolic routes. In the human microbiota study, 2c was converted into M1-M3 and M6. Moreover, interindividual differences in 2c metabolism were observed among the 6 human subjects. Subjects B, C, E, and F could rapidly metabolize 2c to M6, whereas subject D metabolized little 2c, even up to 120 h. In addition, only subjects A, B, and F could cleave the amide bond of 2c or M6 to form the cleaved metabolites. Furthermore, we showed that 2c and its major metabolite M6 are bioactive compounds against human colon cancer cells. M6 was more active than 2c with the half-inhibitory concentration (IC50) of 158 μM and could induce apoptosis at 200 μM.. To our knowledge, the current study demonstrates for the first time that avenanthramide-C can be extensively metabolized by mice and the human microbiota to generate bioactive metabolites.

Topics: Adult; Animals; Apoptosis; Avena; Biotransformation; Body Mass Index; Caffeic Acids; Chromatography, High Pressure Liquid; Coumaric Acids; Feces; Female; HCT116 Cells; Healthy Volunteers; Humans; Male; Mice; Microbiota; ortho-Aminobenzoates; Spectrometry, Mass, Electrospray Ionization

Phenylpropanoid glycosides (PPGs) are natural compounds present in several medicinal plants that have high antioxidant power and diverse biological activities. Because of their low content in plants (less than 5% w/w), several chemical synthetic routes to produce PPGs have been developed, but their synthesis is a time consuming process and the achieved yields are often low. In this study, an alternative and efficient two-step biosynthetic route to obtain natural PPG analogues is reported for the first time. Two galactosides were initially synthesized from vanillyl alcohol and homovanillyl alcohol by a transgalactosylation reaction catalyzed by Kluyveromyces lactis β-galactosidase in saturated lactose solutions with a 30%-35% yield. To synthesize PPGs, the galactoconjugates were esterified with saturated and unsaturated hydroxycinnamic acid derivatives using Candida antarctica Lipase B (CaL-B) as a biocatalyst with 40%-60% yields. The scavenging ability of the phenolic raw materials, intermediates and PPGs was evaluated by the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) method. It was found that the biosynthesized PPGs had higher scavenging abilities when compared to ascorbic acid, the reference compound, while their antioxidant activities were found similar to that of natural PPGs. Moreover, density functional theory (DFT) calculations were used to determine that the PPGs antioxidant mechanism proceeds through a sequential proton loss single electron transfer (SPLET). The enzymatic process reported in this study is an efficient and versatile route to obtain PPGs from different phenylpropanoid acids, sugars and phenolic alcohols.

Topics: Benzyl Alcohols; beta-Galactosidase; Caffeic Acids; Coumaric Acids; Free Radical Scavengers; Fungal Proteins; Galactose; Glycosides; Hydroxides; Kluyveromyces; Lipase; Quantum Theory

A validated method was developed for the simultaneous determination of the hydroxycinnamates caffeic acid (CA), dihydrocaffeic acid (DHCA), ferulic acid (FA), dihydroferulic acid (DHFA), and isoferulic acid (IFA) in human plasma as metabolites derived from coffee consumption. The method includes a protein precipitation step prior to enzymatic hydrolysis of the conjugated metabolites (sulfate, glucuronide, and/or ester) back to their aglycone forms. After liquid-liquid extraction, the reconstituted extract was analysed by high-performance liquid chromatography coupled to negative electrospray ionisation tandem mass spectrometry. Calibration curves were constructed from spiked human plasma samples in the range of 0-4800 nM for each of the targeted analytes. Two internal standards, 3-(4-hydroxyphenyl)-propionic acid (500 nM) and 1,3-dicaffeoylquinic acid (200 nM), were spiked at the beginning of the sample preparation and before analysis, respectively. Good performance data were obtained with limits of detection and quantification of the five hydroxycinnamates ranging between 1-15 nM and 3-50 nM, respectively. Within and between-days precisions were respectively calculated between 8-18% and 8-30% (at 50 nM added initially), between 6-9% and 6-12% (at 200 nM), and between 5-9% and 5-9% (at 500 nM). Precision calculated from different analysts ranged from 18% to 44% (at 50 nM), from 8% to 16% (at 200 nM), and from 4% to 8% (at 500 nM). Using this method, we determined plasma levels in humans and measured the efficiency of deconjugation using our enzymatic cocktail.

Topics: Area Under Curve; Caffeic Acids; Chromatography, Liquid; Cinnamates; Coumaric Acids; Humans; Hydrolysis; Kinetics; Limit of Detection; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

A combinatorial chemistry approach was employed for the design and systematic synthesis of antioxidant-emulsifier bioconjugates to improve antioxidant activity in the interface between oil and water. A combinatorial library of 12 bioconjugates was synthesized from the phenolic antioxidants Trolox (a water-soluble alpha-tocopherol analogue), dihydroferulic acid, dihydrocaffeic acid, and gallic acid in combination with serine ethyl ester, serine lauryl ester, and lauroyl serine by esterification of the serine side chain or amidation, respectively. The bioconjugates were characterized by NMR and mass spectrometry, and each was tested for antioxidant activity by measuring the radical scavenging rate of 2,2-diphenyl-1-picrylhydrazyl (DPPH (*)) in methanol, the radical scavenging rate of DPPH (*) in a heterogeneous solvent system, the rate of oxygen consumption in an oil-in-water emulsion with metmyoglobin initiated oxidation, and the lag phase for diene formation in unilamellar liposomes with free radical initiation in the aqueous phase; each case was compared to the antioxidant activity of the parent antioxidant. In general, the conjugates with longer chain derivatives exhibited improved antioxidative activity in heterogeneous systems, whereas no improvement was observed in homogeneous solution. The rate of oxygen consumption in oil-in-water emulsion was found to decrease with increasing octanol/water partition coefficient, which is suggested to correspond to a saturation of the water/oil interface with antioxidant bioconjugate to approach maximal protection.

Topics: Antioxidants; Caffeic Acids; Chromans; Coumaric Acids; Emulsifying Agents; Esterification; Gallic Acid; Serine

The current growing interest for natural antioxidants has led to a renewed scientific attention for artichoke, due not only to its nutritional value, but, overall, to its polyphenolic content, showing strong antioxidant properties. The major constituents of artichoke extracts are hydroxycinnamic acids such as chlorogenic acid, dicaffeoylquinic acids caffeic acid and ferulic acid, and flavonoids such as luteolin and apigenin glycosides. In vitro studies, using cultured rat hepatocytes, have shown its hepatoprotective functions and in vivo studies have shown the inhibition of cholesterol biosynthesis in human subjects. Several studies have shown the effect on animal models of artichoke extracts, while information on human bioavailability and metabolism of hydroxycinnamates derivatives is still lacking. Results showed a plasma maximum concentration of 6.4 (SD 1.8) ng/ml for chlorogenic acid after 1 h and its disappearance within 2 h (P< 0.05). Peak plasma concentrations of 19.5 (SD 6.9) ng/ml for total caffeic acid were reached within 1 h, while ferulic acid plasma concentrations showed a biphasic profile with 6.4 (SD1.5) ng/ml and 8.4 (SD4.6) ng/ml within 1 h and after 8 h respectively. We observed a significant increase of dihydrocaffeic acid and dihydroferulic acid total levels after 8 h (P<0.05). No circulating plasma levels of luteolin and apigenin were present. Our study confirms the bioavailability of metabolites of hydroxycinnamic acids after ingestion of cooked edible Cynara scolymus L. (cultivar Violetto di Provenza).

Topics: Absorption; Adult; Antioxidants; Caffeic Acids; Chlorogenic Acid; Cinnamates; Cooking; Coumaric Acids; Cynara scolymus; Eating; Female; Humans; Male; Pilot Projects; Plant Extracts