Intestinal absorption of p-coumaric and gallic acids in rats after oral administration

Ferulic acid (FA) and p-coumaric acid (CA) are absorbed by the monocarboxylic acid transporter (MCT) in Caco-2 cells, although gallic acid (GA) is not. Therefore, the MCT is selective for certain phenolic acids. Absorption of orally administered CA and GA in rats was studied to obtain serum pharmacokinetic profiles and to investigate their intestinal absorption characteristics in vivo. Rats were administered 100 micromol/kg body weight of CA and GA, and blood was collected from the portal vein and abdominal artery after administration. CA, GA, and their metabolites were quantified with a highly selective and sensitive coulometric detection method using high-performance liquid chromatography-electrochemical detection. Ingested CA was rapidly absorbed in the gastrointestinal tract in an intact form. The serum concentration of intact CA in the portal vein peaked 10 min after dosing (C(max) was 165.7 micromol/L). In contrast, GA was slowly absorbed, with a t(max) for intact GA of 60 min and a C(max) of 0.71 micromol/L. The area under the curve for intact CA and GA was calculated from the serum concentration profile in the portal vein to be 2991.3 and 42.6 micromol min L(-)(1), respectively. The relative bioavailability of CA against GA was about 70. This is the first demonstration that absorption efficiency of CA is much higher than that of GA in vivo. The absorption characteristics of CA are clearly different from those of GA. These findings are in good agreement with the results obtained in vitro using a Caco-2 cell system.     

Absorption and bioavailability of artepillin C in rats after oral administration

Artepillin C (AC), an active ingredient of Brazilian propolis, permeates intact across Caco-2 cells by transcellular passive diffusion. The permeation of AC across Caco-2 cells is as efficient as that of phenolic acids and the microbial metabolites of poorly absorbed polyphenols, which are actively absorbed by the monocarboxylic acid transporter (MCT) (Biochim. Biophys. Acta 2005, 1713, 138-144). Here, the absorption of orally administered AC in rats has been studied to evaluate its pharmacokinetics and bioavailability in vivo in comparison with those of p-coumaric acid (CA), a substrate of MCT. Rats were given 100 micromol/kg of body weight of AC or CA, and blood was subsequently collected from the portal vein and abdominal artery. AC, CA, and their metabolites were quantified by coulometric detection using HPLC-ECD. The serum concentration of intact AC and CA in the portal vein peaked at 5-10 min after administration, with a C(max) of 19.7 micromol/L for AC and 74.8 micromol/L for CA. The area under the curve (AUC) for intact AC and CA in the portal vein was calculated from the serum concentration as 182.6 and 3057.3 micromol.min.L(-1), respectively. The absorption efficiency of CA was about 17-fold higher than that of AC. Furthermore, the bioavailability of CA was about 278-fold higher than that of AC, and the ratio of AUC in the abdominal artery to AUC in the portal vein was 0.04 and 0.70, for AC and CA, respectively. Thus, AC is likely to be more susceptible to hepatic elimination than is CA. The bioactive compound of AC in vivo should be investigated further.     

Phenolic acids are absorbed from the rat stomach with different absorption rates

The intestinal absorption characteristics of phenolic acids (PAs) have been elucidated in terms of their affinity for the monocarboxylic acid transporter (MCT). Recently, the involvement of the stomach has been implicated in the absorption of polyphenols. The present work demonstrates that the gastric absorption efficiency of each PA is apparently different between various PAs. Various PAs with different affinities for MCT were administered (2.25 mumol) to rat stomach, and then the plasma concentration of the PA was measured. The plasma concentration of ferulic acid (FA) peaked 5 min after administration in the stomach. At 5 min after administration, the plasma concentration of each PA increased in the order: gallic acid = chlorogenic acid < caffeic acid < p-coumaric acid = FA. This order matches their respective affinity for MCT in Caco-2 cells, which we have demonstrated in previous studies. These results indicated that MCT might be involved in the gastric absorption of PAs, similar to the intestinal absorption.     

Difructose anhydride III promotes absorption of the soluble flavonoid alphaG-rutin in rats

A highly soluble quercetin glycoside, alphaG-rutin, is a glucose adduct of insoluble rutin. We examined the effects of difructose anhydride III (DFAIII; di-D-fructofuranosyl 1,2':2,3'-dianhydride) on intestinal absorption of alphaG-rutin by rat experiments. alphaG-rutin, rutin, quercetin, and the quercetin conjugate appeared in the portal blood after an intubation of alphaG-rutin (100 micromol), DFAIII effected higher portal concentrations of alphaG-rutin in portal cannulated rats. In ligated jejunal and ileal loops of rats, alphaG-rutin, rutin, quercetin, and the quercetin conjugate appeared in the intestinal mesenteric blood at both 30 and 60 min in both loops; the concentration of alphaG-rutin was 1.5-3 times higher when absorbed in the presence DFAIII. In the isolated mucosae of the jejunum and ileum, mucosal-to-serosal passage of alphaG-rutin increased with the addition of 100 micromol of DFAIII. These results indicate that alphaG-rutin is absorbed as the intact form and that DFAIII stimulates its absorption in the small intestine.     

Transepithelial Transport of Theasinensins through Caco-2 Cell Monolayers and Their Absorption in Sprague-Dawley Rats after Oral Administration

The aim of this study is to illustrate the in vivo and in vitro absorption of theasinensins B and A that are (-)-epigallocatechin-3-O-gallate (EGCG)-(-)-epigallocatechin (EGC) dimer and EGCG dimer, respectively, and their transport pathway across the intestinal membrane. Our animal study by a single oral administration to rats demonstrated the intact absorption of theasinensins into the blood system, which was estimated to be a >10-fold lower absorption amount than EGCG. The in vitro absorption study indicated that theasinensins can be transported across Caco-2 cell monolayers, while their permeability coefficients were also >10-fold lower than those of EGCG and EGC. Transport experiments using cytochalasin D or quercetin as a tight junction (TJ) modulator and a non-saturable permeation revealed that theasinensins were transported across Caco-2 cells in a TJ paracellular diffusion route. In conclusion, the dimers of condensed catechins, theasinensins B and A, can be absorbed intact into rat blood and transported across Caco-2 cell monolayers probably through a TJ paracellular pathway.     

Transepithelial transport of chlorogenic acid, caffeic acid, and their colonic metabolites in intestinal caco-2 cell monolayers

Both chlorogenic and caffeic acids exhibited nonsaturable transport in Caco-2 cells, whereas caffeic acid also showed proton-coupled polarized absorption. Thus, the absorption efficiency of caffeic acid was greater than that of chlorogenic acid. Polarized transport of caffeic acid was inhibited by substrates of MCT such as benzoic and acetic acids. Almost all of the apically loaded chlorogenic and caffeic acid was retained on the apical side, and the transepithelial flux was inversely correlated with the paracellular permeability of Caco-2 cells. These results indicate that transport was mainly via paracellular diffusion, although caffeic acid was absorbed to a lesser extent by the monocarboxylic acid transporter (MCT). Furthermore, m-coumaric acid and 3-(m-hydroxyphenyl)propionic acid, the main metabolites of chlorogenic and caffeic acid by colonic microflora, competitively inhibited the transport of fluorescein, a known substrate of MCT. This suggests that their absorption could also be mediated by MCT. These findings have exemplified the physiological importance of MCT-mediated absorption in both phenolic acids per se and their colonic metabolites.     

Transepithelial transport of alpha-lipoic acid across human intestinal Caco-2 cell monolayers

Alpha-lipoic acid (LA) is used in dietary supplements or food with antioxidative functions. The mechanism for the intestinal absorption of alpha-lipoic acid was investigated in this study by using human intestinal Caco-2 cell monolayers. LA was rapidly transported across the Caco-2 cell monolayers, this transport being energy-dependent, suggesting transporter-mediated transport to be the mechanism involved. The LA transport was strongly dependent on the pH value, being accelerated in the acidic pH range. Furthermore, such monocarboxylic acids as benzoic acid and medium-chain fatty acids significantly inhibited LA transport, suggesting that a proton-linked monocarboxylic acid transporter (MCT) was involved in the intestinal transport of LA. The conversion of LA to the more antioxidative dihydrolipoic acid was also apparent during the transport process.     

Microbial metabolites of ingested caffeic acid are absorbed by the monocarboxylic acid transporter (MCT) in intestinal Caco-2 cell monolayers

It was previously reported that m-coumaric acid, m-hydroxyphenylpropionic acid (mHPP), and 3,4-dihydroxyphenylpropionic acid (DHPP) are major metabolites of ingested caffeic acid formed by gut microflora and would be transported by the monocarboxylic acid transporter (MCT). We have directly measured their absorption characteristics in Caco-2 cells using a coulometric detection method involving HPLC-ECD. The proton-coupled directional transport of m-coumaric acid, mHPP, and DHPP was observed, and the transport was inhibited by an MCT substrate. The permeation of m-coumaric acid and mHPP was concentration-dependent and saturable: The Michaelis constant for m-coumaric acid and mHPP was 32.5 and 12.9 mM, respectively, and the maximum velocity for m-coumaric acid and mHPP was 204.3 and 91.2 nmol (min)(-1) (mg protein)(-1), respectively. By contrast, the permeation of DHPP was nonsaturable even at 30 mM and was inversely correlated with the paracellular permeability of Caco-2 cells. Our results demonstrate that these compounds are absorbed by the MCT, although DHPP is mainly permeated across Caco-2 cells via the paracellular pathway. MCT-mediated absorption of phenolic compounds per se and their colonic metabolites would exert significant impact on human health.     

Characterization of metabolites of hydroxycinnamates in the in vitro model of human small intestinal epithelium caco-2 cells

Hydroxycinnamic acids are antioxidant phenolic compounds which are widespread in plant foods, contribute significantly to total polyphenol intakes, and are absorbed by humans. The extent of their putative health benefit in vivo depends largely on their bioavailability. However, the mechanisms of absorption and metabolism of these phenolic compounds have not been described. In this study, we used the in vitro Caco-2 model of human small intestinal epithelium to investigate the metabolism of the major dietary hydroxycinnamates (ferulate, sinapate, p-coumarate, and caffeate) and of diferulates. The appearance of metabolites in the medium versus time was monitored, and the various conjugates and derivatives produced were identified by HPLC-DAD, LC/MS, and enzyme treatment with beta-glucuronidase or sulfatase. Enterocyte-like differentiated Caco-2 cells have extra- and intracellular esterases able to de-esterify hydroxycinnamate and diferulate esters. In addition, intracellular UDP-glucuronosyltransferases and sulfotransferases existing in Caco-2 cells are able to form the sulfate and the glucuronide conjugates of methyl ferulate, methyl sinapate, methyl caffeate, and methyl p-coumarate. However, only the sulfate conjugates of the free acids, ferulic acid, sinapic acid, and p-coumaric acid, were detected after 24 h. The O-methylated derivatives, ferulic and isoferulic acid, were the only metabolites detected following incubation of Caco-2 cells with caffeic acid. These results show that the in vitro model system differentiated Caco-2 cells have the capacity to metabolize dietary hydroxycinnamates, including various phase I (de-esterification) and phase II (glucuronidation, sulfation, and O-methylation) reactions, and suggests that the human small intestinal epithelium plays a role in the metabolism and bioavailability of these phenolic compounds.     

Transepithelial transport of microbial metabolites of quercetin in intestinal Caco-2 cell monolayers

m-Hydroxyphenylacetic acid (mHPA), 3,4-dihydroxyphenylacetic acid (DHPA), and 4-hydroxy-3-methoxyphenylacetic acid (HMPA) are major microbial metabolites of quercetin. After administration of quercetin to human subjects, these metabolites are readily detected in blood and urine. mHPA, DHPA, and HMPA are thought to exert protective biological activity within the body due to their antioxidant properties. However, very little work has been published concerning their absorption. I have examined the absorption characteristics of the quercetin metabolites in Caco-2 cells by a coulometric detection method using HPLC-ECD. All of them exhibited nonsaturable transport in Caco-2 cells up to 30 mM, whereas HMPA and mHPA also showed proton-coupled polarized absorption. The proton-coupled directional transport of HMPA and mHPA was inhibited by the substrate of the monocarboxylic acid transporter (MCT). A considerable amount of apically loaded HMPA and mHPA was taken up and transported through to the basolateral side, while almost all of the apically loaded DHPA was retained on the apical side. Furthermore, the transepithelial flux of DHPA was inversely correlated with the paracellular permeability of Caco-2 cells, although those of HMPA and mHPA were almost constant. These results indicate that transport of DHPA was mainly via paracellular diffusion, although HMPA and mHPA were absorbed to some extent by the MCT.     

Combination of lipids and emulsifiers enhances the absorption of orally administered quercetin in rats

The effects of lipids, emulsifiers, and ethanol on the absorption of orally administered quercetin in rats were investigated for its efficient intestinal absorption. Rats were administered 150 micromol/kg quercetin in water supplemented with lipids and/or emulsifiers, or ethanol, and blood was collected from the tail for 6 h after administration. Co-administration of lipids such as lecithin and soybean oil or emulsifiers including sucrose fatty acid ester, polyglycerol fatty acid ester, and sodium taurocholate had no statistically significant effects on quercetin absorption, although these constituents rather increased the accumulation of conjugated forms of quercetin and those of isorhamnetin in rat plasma. However, the combination of lipids and emulsifiers enhanced the absorption of quercetin significantly. Thirty and fifty percent (v/v) of the ethanol in the vehicle raised the efficiency of quercetin absorption in a concentration-dependent manner. Quercetin absorption-enhancing effects of these constituents seemed to be affected by quercetin's solubility in respective vehicles used for the administration. Ethanol is not helpful for the effective absorption of quercetin, as a high concentration is required. In conclusion, a combination of lipids and emulsifiers is necessary for enhancing quercetin absorption.     

Metabolism of anthocyanins by human gut microflora and their influence on gut bacterial growth

Consumption of anthocyanins has been related with beneficial health effects. However, bioavailability studies have shown low concentration of anthocyanins in plasma and urine. In this study, we have investigated the bacterial-dependent metabolism of malvidin-3-glucoside, gallic acid and a mixture of anthocyanins using a pH-controlled, stirred, batch-culture fermentation system reflective of the distal human large intestine conditions. Most anthocyanins have disappeared after 5 h incubation while gallic acid remained constant through the first 5 h and was almost completely degraded following 24 h of fermentation. Incubation of malvidin-3-glucoside with fecal bacteria mainly resulted in the formation of syringic acid, while the mixture of anthocyanins resulted in formation of gallic, syringic and p-coumaric acids. All the anthocyanins tested enhanced significantly the growth of Bifidobacterium spp. and Lactobacillus-Enterococcus spp. These results suggest that anthocyanins and their metabolites may exert a positive modulation of the intestinal bacterial population.     

Uptake of 2S albumin allergens, Ber e 1 and Ses i 1, across human intestinal epithelial Caco-2 cell monolayers

We have investigated the absorption rates of two purified major allergen 2S albumins, Ber e 1 from Brazil nuts (Bertholletia excelsa Humb. & Bonpl.) and Ses i 1 from white sesame seeds (Sesamum indicum L.), across human intestinal epithelial Caco-2 cell monolayers following gastrointestinal digestion in vitro. The transport from apical to basolateral side in cell monolayers was evaluated by RP-HPLC-UV and indirect competitive ELISA methods, being confirmed by western-blotting analysis. Significant amounts (approximately 15-25 nmol micromol(-1) initial amount/h) of intact Ber e 1 and Ses i 1 were found in the basolateral side. The absorption rates of both plant allergens through the cell monolayer were shown to be constant during the whole incubation period (4 h at 37 degrees C), verifying that the permeability of the membrane was not altered by the allergen digests. Our findings revealed that both purified 2S albumin allergens may be able to survive in immunologically reactive forms to the simulated harsh conditions of the gastrointestinal tract to be transported across the Caco-2 cell monolayers, so that they would be able to sensitize the mucosal immune system and/or elicit an allergic response.     

Direct absorption of acylated anthocyanin in purple-fleshed sweet potato into rats

Absorption of acylated anthocyanins in purple-fleshed sweet potato (Ipomoea batatas cv. Ayamurasaki) in rats was studied to obtain evidence that the acylated anthocyanins themselves could exert a physiological function in vivo. Peonidin 3-caffeoylsophoroside-5-glucoside (Pn 3-Caf*sop-5-glc) in purple-fleshed sweet potato was directly absorbed into rat and present as an intact acylated form in plasma. After oral administration of the purple-fleshed sweet potato anthocyanin (PSA) concentrate containing 38.9 micromol of Pn 3-Caf*sop-5-glc/kg of body weight, Pn 3-Caf*sop-5-glc was detected in the plasma, and the C(max) value and t(max) were estimated as 50.0 +/- 6.8 nmol/Lof plasma and 30 min, respectively. Furthermore, the plasma antioxidant capacity was significantly elevated from 58.0 +/- 12.0 to 89.2 +/- 6.8 micromol of Trolox equivalent/L of plasma 30 min after the administration of the PSA concentrate.     

In vitro pharmacokinetic characterization of mulberroside A, the main polyhydroxylated stilbene in mulberry (Morus alba L.), and its bacterial metabolite oxyresveratrol in traditional oral use

Mulberroside A (MulA) is one of the main bioactive constituents in mulberry (Morus alba L.). This study examined the determining factors for previously reported oral pharmacokinetic profiles of MulA and its bacterial metabolite oxyresveratrol (OXY) on in vitro models. When incubated anaerobically with intestinal bacteria, MulA underwent rapid deglycosylation and generated two monoglucosides and its aglycone OXY sequentially. MulA exhibited a poor permeability and predominantly traversed Caco-2 cells via passive diffusion; yet, the permeation of OXY across Caco-2 cells was much more rapid and involved efflux (both p-glycoprotein and MRPs)-mediated mechanisms. Moreover, OXY underwent extensive hepatic glucuronidation; yet, the parent MulA was kept intact in liver subcellular preparations. There was insignificant species difference in intestinal bacterial conversion of MulA and the extent of OXY hepatic glucuronidation between humans and rats, while OXY exhibited a distinct positional preference of glucuronidation in the two species. Overall, these findings revealed a key role of intestinal bacterial conversion in absorption and systemic exposure of MulA and its resultant bacterial metabolite OXY in oral route in humans and rats and warranted further investigational emphasis on OXY and its hepatic metabolites for understanding the benefits of mulberry.     

Antioxidant activity of grains

Epidemiological studies have shown that consumption of whole grains and grain-based products is associated with reduced risk of chronic diseases. The health benefits of whole grains are attributed in part to their unique phytochemical composition. However, the phytochemical contents in grains have been commonly underestimated in the literature, because bound phytochemicals were not included. This study was designed to investigate the complete phytochemical profiles in free, soluble conjugated, and insoluble bound forms, as well as their antioxidant activities in uncooked whole grains. Corn had the highest total phenolic content (15.55 +/- 0.60 micromol of gallic acid equiv/g of grain) of the grains tested, followed by wheat (7.99 +/- 0.39 micromol of gallic acid equiv/g of grain), oats (6.53 +/- 0.19 micromol of gallic acid equiv/g of grain), and rice (5.56 +/- 0.17 micromol of gallic acid equiv/g of grain). The major portion of phenolics in grains existed in the bound form (85% in corn, 75% in oats and wheat, and 62% in rice), although free phenolics were frequently reported in the literature. Ferulic acid was the major phenolic compound in grains tested, with free, soluble-conjugated, and bound ferulic acids present in the ratio 0.1:1:100. Corn had the highest total antioxidant activity (181.42 +/- 0.86 micromol of vitamin C equiv/g of grain), followed by wheat (76.70 +/- 1.38 micromol of vitamin C equiv/g of grain), oats (74.67 +/- 1.49 micromol of vitamin C equiv/g of grain), and rice (55.77 +/- 1.62 micromol of vitamin C equiv/g of grain). Bound phytochemicals were the major contributors to the total antioxidant activity: 90% in wheat, 87% in corn, 71% in rice, and 58% in oats. Bound phytochemicals could survive stomach and intestinal digestion to reach the colon. This may partly explain the mechanism of grain consumption in the prevention of colon cancer, other digestive cancers, breast cancer, and prostate cancer, which is supported by epidemiological studies.     

Tea polyphenols inhibit the transport of dietary phenolic acids mediated by the monocarboxylic acid transporter (MCT) in intestinal Caco-2 cell monolayers

It was previously reported that a fluorescent marker dye, fluorescein, is transported via the monocarboxylic acid transporter (MCT). Fluorescein transport was competitively inhibited by MCT substrates such as ferulic and salicylic acids. Tea polyphenols, in particular, epigallocatechin gallate (EGCg) and epicatechin gallate (ECg), inhibited the transport of fluorescein. Tea polyphenols also inhibited the transport of salicylic and ferulic acids, suggesting tea polyphenols might be substrates of MCT. However, the transepithelial flux of tea polyphenols was much lower than that of the MCT substrates and was inversely correlated with the paracellular permeability of Caco-2 cell monolayers. These findings suggest that tea polyphenols are not substrates but inhibitors of MCT. Furthermore, the transepithelial transport of these polyphenols is mainly via paracellular diffusion. However, directional transport of ECg and EGCg from the basolateral to the apical side was observed, indicating that the behavior of tea polyphenols in the intestinal epithelium is complex.     

Esterase activity able to hydrolyze dietary antioxidant hydroxycinnamates is distributed along the intestine of mammals.

Hydroxycinnamic acids are effective antioxidants and are abundant components of plant cell walls, especially in cereal bran. For example, wheat and rye brans are rich sources of the hydroxycinnamates ferulic acid, sinapic acid, and p-coumaric acid. These phenolics are part of human and animal diets and may contribute to the beneficial effects derived from consumption of cereal bran. However, these compounds are ester linked to the main polymers in the plant cell wall and cannot be absorbed in this complex form. The present work shows that esterases with activity toward esters of the major dietary hydroxycinnamates are distributed throughout the intestinal tract of mammals. In rats, the cinnamoyl esterase activity in the small intestine is derived mainly from the mucosa, whereas in the large intestine the esterase activity was found predominantly in the luminal microflora. Mucosa cell-free extracts obtained from human duodenum, jejunum, and ileum efficiently hydrolyzed various hydroxycinnamoyl esters, providing the first evidence of human cinnamoyl esterase(s). This study first demonstrates the release by human colonic esterase(s) (mostly of microbial origin) of sinapic acid and p-coumaric acid from rye and wheat brans. Hydrolysis by intestinal esterase(s) is very likely the major route for release of antioxidant hydroxycinnamic acids in vivo.     

Increase of antioxidative potential of rat plasma by oral administration of proanthocyanidin-rich extract from grape seeds.

The effect of a single oral administration of proanthocyanidins, oligomeric and polymeric polyhydroxyflavan-3-ol units, on the antioxidative potential of blood plasma was studied in rats. Proanthocyanidin-rich extract from grape seeds was administered by intragastric intubation to fasted rats at 250 mg/kg of body weight. The plasma obtained from water- or proanthocyanidin-administered rats was oxidized by incubation with copper sulfate or 2, 2'-azobis(2-amidinopropane) dihydrochloride (AAPH) at 37 degrees C, and the formation of cholesteryl ester hydroperoxides (CE-OOH) was followed. The plasma obtained from proanthocyanidin-administered rats was significantly more resistant against both copper ion-induced and AAPH-induced formation of CE-OOH than that from control rats. The lag phase in the copper ion-induced oxidation of rat plasma was remarkably increased at 15 min after administration of proanthocyanidins and reached a maximum level at 30 min. When the plasma from proanthocyanidin-administered rat was hydrolyzed by sulfatase and beta-glucuronidase following analysis by high-performance liquid chromatography with electrochemical detection, metabolites of proanthocyanidins occurred in rat plasma at 15 min after administration, three peaks of which were identified as gallic acid, (+)-catechin, and (-)-epicatechin. These results suggest that the intake of proanthocyanidins, the major polyphenols in red wine, increases the resistance of blood plasma against oxidative stress and may contribute to physiological functions of plant food including wine through their in vivo antioxidative ability.     

Antioxidant properties of Fusarium head blight-resistant and -susceptible soft red winter wheat grains grown in Virginia

Fusarium head blight (FHB) has emerged as a major threat to wheat crops around the world, and it has been hypothesized that wheat antioxidants may play a role against Fusarium infections. The current study aimed to determine antioxidant properties of FHB-resistant wheat grains as compared to susceptible wheat. The wheat samples were collected from a single growing location (Warsaw, VA) and the same growing season. The results showed that both FHB-resistant and -susceptible wheat grains exerted strong radical scavenging activities against DPPH* radical [0.91-1.53 micromol of Trolox equivalents (TE)/g], peroxyl radical (15.5-24.5 micromol of TE/g), and hydroxyl radical (15.7-35.8 micromol of TE/g). Their total phenolic contents ranged from 888 to 1117 microg of gallic acid equivalents (GAE)/g. Five phenolic acids including ferulic, syringic, vanillic, caffeic, and p-coumaric acids were determined in soluble and insoluble fractions of wheat grains, altogether with a range of 219-389 microg/g. On average, the FHB-resistant wheat group showed significantly higher average values in DPPH* and hydroxyl radicals scavenging activities (30 and 41% higher, respectively) than the FHB-susceptible wheat group.