Absorption of ferulic acid from low-alcohol beer

Flavonoids and monophenolic compounds have been well-described over recent years for their properties as antioxidants and scavengers of reactive oxygen and nitrogen species. A number of epidemiological studies implicate a role for flavonoids in reducing the risk of coronary heart disease. In particular, the focus has been on flavonol-rich fruit and vegetables and flavonoid-rich beverages, especially tea and red wine. Mechanisms of protection are unclear since the absorption, distribution, metabolism and elimination of dietary phenolics have not yet been extensively investigated. Here we report the bioavailability of ferulic acid, 4-hydroxy-3-methoxy-cinnamic acid, the major hydroxycinnamate in beer. Studies of the pharmacokinetics of urinary excretion of ferulic acid from low alcohol beer consumption in humans have been undertaken. The results show that ferulic acid is absorbed with a peak time for maximal excretion of ca. 8 h and the mean cumulative amount excreted is 5.8±3.2 mg. These findings are consistent with the uptake of ferulic acid from dietary sources, such as tomatoes, and suggest that ferulic acid is more bioavailable than individual dietary flavonoids and phenolics so far studied.     

Novel biomarkers of the metabolism of caffeic acid derivatives in vivo

The purpose of this study was to investigate biomarkers of the bioavailability and metabolism of hydroxycinnamate derivatives through the determination of the pharmacokinetics of their urinary elimination and identification of the metabolites excreted. Coffee was used as a rich source of caffeic acid derivatives and human supplementation was undertaken. The results show a highly significant increase in the excretion of ferulic, isoferulic, dihydroferulic acid (3-(4-hydroxy-3-methoxyphenyl)-propionic acid), and vanillic acid postsupplementation relative to the levels presupplementation. Thus, ferulic, isoferulic, and dihydroferulic acids are specific biomarkers for the bioavailability and metabolism of dietary caffeic acid esters. Isoferulic acid is a unique biomarker as it is not a dietary component, however, dihydroferulic acid may well derive from other flavonoids with a structurally related B-ring. 3-Hydroxyhippuric acid has also been identified as an indicator for bioavailability and metabolism of phenolic compounds, and shows a highly significant excretion increase postsupplementation. The results reveal isoferulic acid (and possibly dihydroferulic acid) as novel markers of caffeoyl quinic acid metabolism.     

A reevaluation of the peroxynitrite scavenging activity of some dietary phenolics

Peroxynitrite is implicated in many diseases. Hence, there is considerable interest in potential therapeutic peroxynitrite scavengers. Diet-derived phenolics have been claimed to be powerful peroxynitrite scavengers. However, the reactivity of peroxynitrite can be significantly modified by bicarbonate and this has not been considered in evaluations of the scavenging activity of phenols. Bicarbonate (25 mM) significantly decreased the ability of several phenolic compounds (caffeic acid, o- and p-coumaric acid, gallic acid, ferulic acid) but not others (catechin and epicatechin) to inhibit peroxynitrite-mediated tyrosine nitration. Bicarbonate (25 mM) also decreased the ability of catechin, epicatechin, quercetin and ferulic acid but not chlorogenic acid, gallic acid, caffeic acid and o-coumaric acid to inhibit peroxynitrite-mediated alpha(1)-antiproteinase inactivation. These results show that physiological concentrations of bicarbonate substantially modify the ability of dietary phenolics to prevent peroxynitrite-mediated reactions. When assessing compounds for peroxynitrite scavenging, experiments should be conducted in the presence of bicarbonate to avoid misleading results.     

Randomized controlled trial of dietary intervention: association between level of urinary phenolics and anti-mutagenicity

We have undertaken a randomized trial to confirm the ability of a class of phenolics, flavonoids, to increase urinary anti-mutagenicity in smokers. Ninety heavy smokers were recruited and randomly assigned to three groups, who were given three different diets. One diet was rich in flavonoids, but not based on supplementation ('flavonoid'), one was a normal iso-caloric diet with an adequate administration of fruit and vegetables ('normal'), and one was based on supplementation of flavonoids in the form of green tea and soy products ('supplement'). The urinary anti-mutagenicity-as inhibiting effect of the urinary extracts on the mutations induced by MeIQx-was measured in Salmonella typhimurium YG1024 in the presence of liver S9 from male Sprague-Dawley rats treated with Aroclor 1254. The amount of total phenolics in the urinary extracts was measured by use of spectrometric analysis. We found that important dietary modifications can be achieved through special recipes and instructions given by a cook during an intensive course. The intervention was focused on increasing the flavonoid intake, and it was successful in that respect. In fact, differences in flavonoid intake were appreciated mainly between the first group (normal diet) and the other two (flavonoid-rich and supplemented diet), suggesting that dietary modification can be as effective as supplementation. However, both urinary anti-mutagenicity and the amounts of urinary phenolics did not change as a consequence of the trial. These results suggest that only a small fraction of urinary phenolics is influenced by dietary changes in the intake of flavonoids, and that most urinary anti-mutagens and phenolics are metabolites of dietary flavonoids, whose formation is more affected by the activity and diversity of bacterial flora in the colon than by the quantity and type of intake. A strong correlation was found between urinary phenolics and anti-mutagenicity in all the groups involved in the trial. Such correlation was not explained by dietary variables.     

Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties

Flavonoids, including isoflavones, are natural components in our diet and, with the burgeoning interest in alternative medicine, are increasingly being ingested by the general population. Plant phenolics, which form moieties on flavonoid rings, such as gallic acid, are also widely consumed. Several beneficial properties have been attributed to these dietary compounds, including antioxidant, anti-inflammatory, and anticarcinogenic effects. Flavonoid preparations are marketed as herbal medicines or dietary supplements for a variety of alleged nontoxic therapeutic effects. However, they have yet to pass controlled clinical trials for efficacy, and their potential for toxicity is an understudied field of research. This review summarizes the current knowledge regarding potential dietary flavonoid/phenolic-induced toxicity concerns, including their pro-oxidant activity, mitochondrial toxicity (potential apoptosis-inducing properties), and interactions with drug-metabolizing enzymes. Their chemopreventive activity in animal in vivo experiments may result from their ability to inhibit phase I and induce phase II carcinogen metabolizing enzymes that initiate carcinogenesis. They also inhibit the promotion stage of carcinogenesis by inhibiting oxygen radical-forming enzymes or enzymes that contribute to DNA synthesis or act as ATP mimics and inhibit protein kinases that contribute to proliferative signal transduction. Finally, they may prevent tumor development by inducing tumor cell apoptosis by inhibiting DNA topoisomerase II and p53 downregulation or by causing mitochondrial toxicity, which initiates mitochondrial apoptosis. While most flavonoids/phenolics are considered safe, flavonoid/phenolic therapy or chemopreventive use needs to be assessed as there have been reports of toxic flavonoid-drug interactions, liver failure, contact dermatitis, hemolytic anemia, and estrogenic-related concerns such as male reproductive health and breast cancer associated with dietary flavonoid/phenolic consumption or exposures.     

Ferulic acid excretion as a marker of consumption of a French maritime pine (Pinus maritima) bark extract

French maritime pine (Pinus maritima) bark extract (PBE) is a polyphenol-rich food supplement patented under the name of Pycnogenol and known to have strong antioxidant activity and different beneficial effects on human health. Although its biological properties have begun to be extensively studied both in vitro, in laboratory animals and more recently in humans, little is known about its bioavailability. The present study investigated the urinary excretion of free and conjugated ferulic acid, present in quantitatively detectable amounts in PBE, after oral PBE administration to human subjects. Eleven healthy adult subjects (4 women and 7men) consumed either a single dose (200 mg PBE) or two doses of PBE (100 and 200 mg, respectively) within a 48-h interval. Two days before the oral administration of PBE and during the urine sample collection period volunteers adhered to a diet low in polyphenols. Aliquots of all urine production were collected over 24 h. Free and conjugated ferulic acid was assessed in urine by HPLC using diode array detection. A close association between the dietary intake of PBE and the urinary excretion of ferulic acid was detected. Moreover, the results indicate that a considerable proportion of ferulic acid is excreted as glucuronide or sulfate after PBE consumption, varying over the range 2 to 20% between individuals. The kinetics of excretion associated with the administration of 100 mg PBE was quite similar to that obtained after 200 mg PBE. A a biphasic trend was evident in a number of subjects. All subjects studied here displayed a significant, although variable level of excretion of ferulic acid after supplementation with PBE, Thus, the data provide evidence that at least a part of the phenolic components of PBE are absorbed, metabolized, and eliminated by humans.     

Caffeic acid derivatives in artichoke extract are metabolised to phenolic acids in vivo

The purpose of this study was to investigate the absorption and metabolism of hydroxycinnamates from artichoke extract by determining the urinary excretion of the conjugates. Ten healthy, non smoking volunteers (5 female, 5 male) were given three capsules containing artichoke extract every 4 h (0, 4, 8h) following two days of a low-polyphenol diet. One capsule contained 320 mg of artichoke extract equivalent to 34.3 ± 0.6 mg/g hydroxycinnamates (caffeic acid derivatives) and 5.6 ± 0.1 mg/g flavonoids. Polyphenols and phenolic acids present in the artichoke extract were not detected in the urine either as conjugates or aglycones. However, ferulic, isoferulic, dihydroferulic and vanillic acid were identified as major metabolites after β-glucuronidase treatment of urine. The amount excreted as well as the ratio to that of creatinine, a biomarker for the general excretion rate, increased significantly on the study day compared to the presupplementation day. Thus, the caffeic acid esters found in the artichoke extract capsule are absorbed, metabolised and excreted as methylated phenolic acids such as ferulic, isoferulic, dihydroferulic and vanillic acid.     

Phenolics removal from transgenic Lemna minor extracts expressing mAb and impact on mAb production cost

Transgenic Lemna minor has been used successfully to produce several biotherapeutic proteins. For plant-produced mAbs specifically, the cost of protein A capture step is critical as the economic benefits of plant production systems could be erased if the downstream processing ends up being expensive. To avoid potential modification of mAb or fouling of expensive protein A resins, a rapid and efficient removal of phenolics from plant extracts is desirable. We identified major phenolics in Lemna extracts and evaluated their removal by adsorption to PVPP, XAD-4, IRA-402, and Q-Sepharose. Forms of apigenin, ferulic acid, and vitexin comprised ～ 75% of the total phenolics. Screening of the resins with pure ferulic acid and vitexin indicated that PVPP would not be efficient for phenolics removal. Analysis of the breakthrough fractions of phenolics adsorption to XAD-4, IRA-402, and Q-Sepharose showed differences in adsorption with pH and in the type of phenolics adsorbed. Superior dynamic binding capacities (DBC) were observed at pH 4.5 than at 7.5. To evaluate the cost impact of a phenolics removal step before protein A chromatography, a mAb purification process was simulated using SuperPro Designer 7.0. The economic analysis indicated that addition of a phenolics adsorption step would increase mAb production cost only 20% by using IRA-402 compared to 35% for XAD-4 resin. The cost of the adsorption step is offset by increasing the lifespan of protein A resin and a reduction of overall mAb production cost could be achieved by using a phenolics removal step.     

Accumulation of cell wall-bound phenolic metabolites and their upliftment in hairy root cultures of tomato (<Emphasis Type="Italic">Lycopersicon esculentum</Emphasis> Mill.)

Alkaline hydrolysis of cell wall material of tomato hairy roots yielded ferulic acid as the major phenolic compound. Other phenolics were 4-hydroxybenzoic acid, vanillic acid, 4-hydroxybenzaldehyde, vanillin and 4-coumaric acid. The content of phenolics was much higher at the early stage of hairy root growth. The ferulic acid content decreased up to 30 days and then sharply increased to 360 microg/g at 60 days of growth. Elicitation of hairy root cultures with Fusarium mat extract (FME) increased ferulic acid content 4-fold after 24 h. As the pathogen-derived elicitors have specific receptors in plants, FME may thus be used for inducing resistance against Fusarium oxysporum f. sp. lycopersici.     

Biotransformation of corn bran derived ferulic acid to vanillic acid using engineered Pseudomonas putida KT2440

Abstract

Ferulic acid is a fraction of the phenolics present in cereals such as rice and corn as a component of the bran. Substantial amounts of waste bran are generated by the grain processing industry and this can be valorized via extraction, purification and conversion of phenolics to value added chemical products. Alkaline alcohol based extracted and purified ferulic acid from corn bran was converted to vanillic acid using engineered Pseudomonas putida KT2440. The strain was engineered by rendering the vanAB gene nonfunctional and obtaining the mutant defective in vanillic acid metabolism. Biotransformation of ferulic acid using resting Pseudomonas putida KT2440 mutant cells resulted in more than 95?±?1.4% molar yield from standard ferulic acid; while the corn bran derived ferulic acid gave 87?±?0.38% molar yield. With fermentation time of less than 24?h the mutant becomes a promising candidate for the stable biosynthesis of vanillic acid at industrial scale.     

Caffeic acid derivatives in artichoke extract are metabolised to phenolic acids in vivo

The purpose of this study was to investigate the absorption and metabolism of hydroxycinnamates from artichoke extract by determining the urinary excretion of the conjugates. Ten healthy, non smoking volunteers (5 female, 5 male) were given three capsules containing artichoke extract every 4 h (0, 4, 8h) following two days of a low-polyphenol diet. One capsule contained 320 mg of artichoke extract equivalent to 34.3 ± 0.6 mg/g hydroxycinnamates (caffeic acid derivatives) and 5.6 ± 0.1 mg/g flavonoids. Polyphenols and phenolic acids present in the artichoke extract were not detected in the urine either as conjugates or aglycones. However, ferulic, isoferulic, dihydroferulic and vanillic acid were identified as major metabolites after β-glucuronidase treatment of urine. The amount excreted as well as the ratio to that of creatinine, a biomarker for the general excretion rate, increased significantly on the study day compared to the presupplementation day. Thus, the caffeic acid esters found in the artichoke extract capsule are absorbed, metabolised and excreted as methylated phenolic acids such as ferulic, isoferulic, dihydroferulic and vanillic acid.     

Urinary excretion of hydroxycinnamates and flavonoids after oral and intravenous administration.

The urinary recoveries of the hydroxycinnamates, ferulic acid (3-methoxy, 4-hydroxy cinnamic acid), and chlorogenic acid (the quinic acid ester of 3,4-dihydroxycinnamic acid), and three structurally related flavonoids were studied in the rat. For the latter, the aglycone quercetin was compared with its 3-glucoside (isoquercitrin) and 3-rhamnoglucoside (rutin). Doses of 50 mg/kg were administered via the oral and intravenous routes and urine collected over the subsequent 24-h period. Reverse phase HPLC with photo-diode array detection was used to analyze the unchanged compound and their metabolites excreted in the urine. Ferulic acid and isoquercitrin were orally absorbed (5.4 and 0.48% of administered dose, respectively) and are therefore bioavailable. In contrast, neither unchanged chlorogenic acid, rutin, quercetin, nor the conjugated metabolites in the form of glucuronide or sulphate were detected in the urine after oral dosing. All the flavonoids studied produced low total urinary recoveries after intravenous administration, 9.2% for quercetin-3-rhamnoglucoside, 6.7% for the 3-glucoside, and 2.4% for the aglycone, indicating that extensive metabolism to low molecular weight compounds or excretion via other routes may be occurring. Overall it can be stated that renal excretion is not a major pathway of elimination for intact flavonoids and hydroxycinnamates in the rat.     

Anti-apoptotic activity of caffeic acid, ellagic acid and ferulic acid in normal human peripheral blood mononuclear cells: a Bcl-2 independent mechanism

Polyphenols have been shown to induce apoptosis in a variety of tumor cells including leukemia both in vitro and in vivo. However, their action on normal human peripheral blood mononuclear cells (PBMCs) during oxidative stress remains to be explored. In this study, we have evaluated the anti-apoptotic and radical scavenging activities of dietary phenolics, namely caffeic acid (CA), ellagic acid (EA) and ferulic acid (FA). H2O2-induced apoptosis in normal human PBMCs was assayed by phosphotidylserine externalization, nucleosomal damage and DNA fragmentation. Incubation of PBMCs with 5 mM H2O2 led to increased Annexin-V binding to externalized phosphatidyl serine (PS), an event of pre-apoptotic stage of the cell. Peripheral blood mononuclear cells pretreated with phenolics could resist H2O2-induced apoptotic damage. Caffeic acid (60 and 120 microM) and EA (100 and 200 microM) caused no change in externalization of PS, whereas FA (100 and 200 microM) increased externalization of PS in PBMCs treated with H2O2. The effects of phenolics were abolished to a large extent by culturing the PBMCs for 24 h after washing the phenolics from the medium. Inhibitory activities of these phenolics on lipid peroxidation were in the order of EA相似文献   

Human fecal water content of phenolics: the extent of colonic exposure to aromatic compounds

Phenolic compounds are not completely absorbed in the small intestine and so enter the colon, where they might exert physiological effects. To identify phenolics that are present in normal human colon, fecal water was prepared from 5 free-living volunteers with no dietary restrictions and analyzed by gas chromatography-mass spectrometry. Daily measurements were also performed on a single individual to examine the variation more closely. Levels of polyphenols were variable between individuals. Naringenin and quercetin had mean concentrations of 1.20 and 0.63 microM. All other flavonoids examined were present < or =0.17 microM. Simple phenolic and other aromatic acids were present at much higher concentrations. The major components were phenylacetic acid, 479 microM; 3-phenylpropionic acid, 166 microM; 3-(4-hydroxy)-phenylpropionic acid, 68 microM; 3,4-dihydroxycinnamic acid, 52 microM; benzoic acid, 51 microM; 3-hydroxyphenylacetic acid, 46 microM; and 4-hydroxyphenylacetic acid, 19 microM. Other phenolic acids ranged from 0.04 to 7 microM. Decreased dietary phenolic intake caused a decrease in polyphenol and monophenolic acid concentration in fecal water 24 h later. This study is the first to measure the range of aromatic compounds in human fecal water and demonstrates that phenolic acid concentrations are high. The biological effects of phenolics may play an important role in colon function.     

Antioxidant actions of plant foods: Use of oxidative DNA damage as a tool for studying antioxidant efficacy

Plant-food-derived antioxidants and active principles such as flavonoids, hydroxycinnamates (ferulic acid, chlorogenic acids, vanillin etc.), β-carotene and other carotenoids, vitamin E, vitamin C, or rosemary, sage, tea and numerous extracts are increasingly proposed as important dietary antioxidant factors. In this endeavor, assays involving oxidative DNA damage for characterizing the potential antioxidant actions are suggested as in vitro screens of antioxidant efficacy. The critical question is the bioavailability of the plant-derived antioxidants.     

Antioxidant actions of plant foods: Use of oxidative DNA damage as a tool for studying antioxidant efficacy

Plant-food-derived antioxidants and active principles such as flavonoids, hydroxycinnamates (ferulic acid, chlorogenic acids, vanillin etc.), β-carotene and other carotenoids, vitamin E, vitamin C, or rosemary, sage, tea and numerous extracts are increasingly proposed as important dietary antioxidant factors. In this endeavor, assays involving oxidative DNA damage for characterizing the potential antioxidant actions are suggested as in vitro screens of antioxidant efficacy. The critical question is the bioavailability of the plant-derived antioxidants.     

Phenolics from Chilean Bee Bread Exhibit Antioxidant and Antibacterial Properties: The First Prospective Study

Bee bread (BB) is a beehive product generated upon fermentation of pollen combined with flower nectar and glandular secretions. The potential application of BB is related to its nutritional and functional components, including phenolic compounds. This is the first prospective study on palynological parameters, phenolics, antioxidant, and antibacterial activity of Chilean bee bread in vitro. The tested material exhibited high levels of phenolics (1340±186 mg GAE/100 g BB) and showed antioxidant capacity as determined by the FRAP (51±2 μmol Trolox equivalent/g BB) and ORAC-FL (643±64 μmol Trolox equivalent/g BB) and antibacterial activity against Streptococcus pyogenes. Furthermore, the phenolic acids and flavonoids was determined using liquid chromatography-mass spectrometry, and the concentration was determined using liquid chromatography with diode array detection. Kaempferol, quercetin, ferulic acid, and rutin were the main phenolics found. This study demonstrates the bioactive potential of Chilean BB and supports the evidence that this bee product is a promising source of antioxidants and antimicrobial compounds.     

Detoxication of some naturally occuring phenolics by prairie voles: a rapid assay of glucuronidation metabolism

Mammals detoxicate many phenolic compounds by conjugation with glucuronic acid, and this increases urinary excretion of components of the glucuronic acid pathway. We evaluated a measure of total uronic acid excretion by prairie voles as an index of detoxication of phenolic compounds. Various levels of quercetin and tannic acid were fed at two levels of protein to weanling prairie voles. Uronic acid excretion increased greatly with increased concentrations of dietary phenolics, but was not a simple linear function of phenolic concentration. Voles fed low protein diets excreted more uronic acids than voles fed high protein diets, apparently because of more phenolic-protein complexing in the latter case. Measurement of uronic acid output appears to provide a simple, non-invasive index of detoxication loads in these mammalian herbivores.     

Relationships between phenolics-conjugated polyamines and sensitivity of sugarcane to smut (Ustilago scitaminea)

Infection of sugarcane buds (var. Barbados 42231) with teliospores of Ustilago scitaminea changes the pattern of polyamine conjugation in several organs of 2-month-old plants. Stalks of infected plants contain SH-spermidine that does not occur in the healthy organ. Similar results have been obtained for SH-spermine in the first expanded leaf and in the stem. The amount of SH-cadaverine in the first expanded leaf, roots and stem of infected plants is always higher than that found for healthy plants. Some phenolics are also associated with different polyamine fractions. So, the amount of p-hydroxybenzoic acid in both SH and PH fractions of polyamines extracted from the root increases after infection. Syringic acid is the main phenol associated with the PH fraction in the first expanded leaf of infected plants, whereas this phenol is mainly associated with both SH and PH fractions isolated from the stem and the whip. Infection enhances conjugation of p-courmaric acid to PH polyamines, whereas caffeic acid appears in the SH fraction in leaf, root and stem. However, ferulic acid seems to be the main hydroxycinnamic acid derivative in the whip. Chlorogenic acid is associated with the SH fraction from the stem of healthy plants although this changes to free phenolics after infection.Key words:Saccharum officinarum, Ustilago sciaminea, phenolics, polyamines.