Absorption of 6-O-caffeoylsophorose and its metabolites in Sprague-Dawley rats detected by electrochemical detector-high-performance liquid chromatography and electrospray ionization-time-of-flight-mass spectrometry methods

Absorption and metabolism of a natural compound, 6-O-caffeoylsophorose (CS) from acylated anthocyanins in a red vinegar fermented with purple sweet potato, were clarified. The absorption of CS and conjugated CS in blood from orally administrated Sprague-Dawley rats at a dose of 400 mg/kg was investigated by electrochemical detection-high performance liquid chromatography. As a result, CS was successfully detected in rat plasma (AUC(0-6h), 108.6 ± 8.1 nmol h/mL) and was found to be an intact absorbable polyphenol. In addition, half of the absorbed CS was detected as its conjugates (AUC(0-6h), 50.7 ± 5.7 nmol h/mL) as well as caffeic and ferulic acids from CS. By a time-of-flight-mass spectrometric analysis of CS-administered plasma sample, glucuronide and methylated conjugates of CS were identified, in addition to glucuronide, methylated, or sulfate conjugates of caffeic and ferulic acids. Consequently, CS was absorbed in intact form into rat blood and partly degraded to caffeic and ferulic acids or metabolized by glucuronidation, methylation, or sulfatation.     

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.     

Occurrence of orally administered mulberry 1-deoxynojirimycin in rat plasma

1-deoxynojirimycin (DNJ), a potent glucosidase inhibitor, is a characteristic constituent of the mulberry leaf. Dietary mulberry DNJ may be beneficial for the suppression of abnormally high blood glucose levels, thereby preventing diabetes mellitus. Although there is considerable interest in the effects of mulberry DNJ, the intestinal absorption and pharmacokinetic profile of orally administered mulberry DNJ have never been characterized. In this study, we developed a method for determining the level of plasma DNJ by hydrophilic interaction chromatography coupled to a mass spectrometric detector (HILIC-MS) to investigate the absorption and metabolism of orally administered mulberry DNJ in rats. DNJ was separated from plasma extract on a TSK gel Amide-80 column, a representative column for HILIC. At postcolumn, DNJ was concurrently detected and identified by MS. The plasma DNJ concentration in fasted rats was below the detection limit [<1 microg (6 nmol)/mL]; however, the concentration reached a maximum [15 microg (92 nmol)/mL] 30 min after the administration of mulberry DNJ (110 mg/kg of body weight), and the DNJ concentration decreased rapidly thereafter. When the rats received different amounts of mulberry DNJ (1.1, 11, and 110 mg/kg of body weight), dose-dependent incorporation of DNJ into the plasma was confirmed. We did not detect any DNJ metabolites in the plasma. These findings indicate that orally administered mulberry DNJ is absorbed as an intact form from the alimentary tract and then is quickly excreted from the body. The developed HILIC-MS method could be applied in determining levels of DNJ in urine and tissues, and therefore, the method would be a powerful tool for studying the metabolic fate of mulberry DNJ as well as its bioavailability.     

Absorption of chlorogenic acid and caffeic acid in rats after oral administration

Absorption of orally administered chlorogenic acid (5-caffeoylquinic acid) and caffeic acid in rats was studied to obtain plasma pharmacokinetic profiles of their metabolites. Rats were administered 700 micromol/kg body weight of chlorogenic or caffeic acid, and blood was collected from the tail for 6 h after administration. Ingested caffeic acid was absorbed from the alimentary tract and was present in the rat blood circulation in the form of various metabolites. On the other hand, only traces of metabolites, supposedly caffeic and ferulic acids conjugates, were detected in rat plasma for 6 h after chlorogenic acid administration. Chlorogenic acid and small amounts of caffeic acid were found in the small intestine for 6 h after chlorogenic acid administration. These results suggest that chlorogenic acid is not well absorbed from the digestive tract, unlike caffeic acid, and subject to almost no structural changes to the easily absorbed forms.     

Ingested delphinidin-3-rutinoside is primarily excreted to urine as the intact form and to bile as the methylated form in rats

Many reports have described the bioavailability of anthocyanins; however, most of these reports investigated only the amount of anthocyanins excreted in urine. In the present study, we calculated the pharmacokinetic bioavailability of anthocyanins in rats by measuring the plasma concentration of delphinidin-3-rutinoside that had been administered orally or intravenously. Delphinidin-3-rutinoside was primarily absorbed in the blood and excreted into urine as unmetabolized forms with a T(max) of 26.3 min and a C(max) of 0.285 +/- 0.071 micromol/L. We detected small amounts of the metabolite 4'-O-methyl-delphinidin-3-rutinoside in the plasma, but we detected neither anthocyanidin (aglycone) nor glucuro- or sulfoconjugates. For the 8 h period after intake, delphinidin-3-rutinoside and 4'-O-methyl-delphinidin-3-rutinoside were excreted to urine at 795 +/- 375 and 12.3 +/- 2.91 nmol, respectively. Relative to intravenous injection, oral administration of delphinidin-3-rutinoside resulted in complete bioavailability (0.49 +/- 0.06%). Analysis of delphinidin-3-rutinoside plasma concentrations in bile cannulated rats revealed that, for the 8-h period after intake, the intact delphinidin-3-rutinoside excretion ratio in bile was 11% of the excretion ratio of 4'-O-methyl-delphinidin-3-rutinoside, 1.91 +/- 0.35 nmol versus 17.4 +/- 8.67 nmol, respectively. Setting the bile duct cannulation in a Bollman-type cage, however, significantly increased the bioavailability of orally administered delphinidin-3-rutinoside (18.14 +/- 6.24%). This effect appears to stem immobilization stress by reducing gastrointestinal motility. The cumulative excretion of delphinidin-3-rutinoside and 4'-O-methyl-delphinidin-3-rutinoside in urine and bile was 2.67 +/- 1.24% (w/w) of the dose ingested. Studies report that several metabolites are formed after oral ingestion of anthocyanins. Examples include glucuronyl from cyanidin-3-glucoside and both glucuronyl and sulfate conjugates from pelargonidin-3-glucoside. Our results indicate that delphinidin-3-rutinoside might be metabolized differently from cyanidin-3-glucoside and pelargonidin-3-glucoside.     

Involvement of Ca2+ in the inhibition by crocetin of platelet activity and thrombosis formation

Crocetin, a unique carotenoid with potent antioxidative and anti-inflammatory activities, is a major ingredient of saffron used as an important spice and food colorant in various parts of the world. In the present study, the effects of crocetin on platelet activity and thrombosis formation were systematically investigated. Crocetin showed a dose-dependent inhibition of platelet aggregation induced by ADP, collagen, but not by arachidonic acid (AA). Crocetin significantly attenuated dense granule release, while neither platelets adhesion to collagen nor cyclic AMP level was altered by crocetin. Pretreatment with crocetin was confirmed to partially inhibit Ca (2+) mobilization via reducing both intracellular Ca (2+) release and extracellular Ca (2+) influx. Besides that, crocetin prolonged the occlusive time in electrical stimulation-induced carotid arterial thrombosis. These findings suggest that the favorable impacts of crocetin on platelet activity and thrombosis formation may be related to the inhibition of Ca (2+) elevation in stimulated platelets.     

Identification and quantification of the conjugated metabolites derived from orally administered hesperidin in rat plasma

Hesperidin is a biologically effective flavonoid. Several studies have reported that dietary hesperidin was converted to conjugated metabolites, such as hesperetin-glucuronides and sulfoglucuronides, during absorption and metabolism. However, the chemical structures of the conjugated metabolites, especially the sites of glucuronidation and sulfoglucuronidation in plasma, were unconfirmed. Therefore, the concentrations of the metabolites conjugated at various sites in plasma could not be individually quantified. In the present study, we identified the chemical structures and concentrations of the major conjugated metabolites in rat plasma after oral administration of hesperidin. Two hesperetin-glucuronides were prepared and identified as hesperetin-7-O-beta-D-glucuronide and hesperetin-3'-O-beta-D-glucuronide. Using these authentic compounds, the concentrations of hesperetin-7-O-beta-D-glucuronide and hesperetin-3'-O-beta-D-glucuronide in rat plasma were individually determined by liquid chromatography-mass spectrometry. In rat plasma, hesperetin-glucuronides were primarily comprised of hesperetin-7-O-beta-D-glucuronide and hesperetin-3'-O-beta-D-glucuronide. The concentration of hesperetin-7-O-beta-D-glucuronide was slightly higher than that of hesperetin-3'-O-beta-D-glucuronide. Furthermore, not only hesperetin conjugates but also homoeriodictyol conjugates were observed in rat plasma. The present study is the first report elucidating the chemical structures and changes in individual concentrations in rat plasma of glucuronides derived from orally administered hesperidin.     

Metabolism of theanine, gamma-glutamylethylamide, in rats

The metabolism of theanine, one of the major amino acid components in tea (Camellia sinensis), was studied in rats. High-performance liquid chromatography (HPLC) with fluorometric detection was used to evaluate the nature of theanine's metabolites in plasma, urine, and tissues. In the urine samples collected after administration of 100, 200, and 400 mg each of theanine, intact theanine, L-glutamic acid, and ethylamine, these compounds were detected in a dose-dependent manner. When 200 mg of theanine was orally administered to rats, the plasma concentrations of theanine and ethylamine reached their highest levels about 0.5 and 2 h after administration, respectively. It seems most likely that the enzymatic hydrolysis of theanine to glutamic acid and ethylamine was accomplished in the kidney. These results indicate that orally administered theanine is absorbed through the intestinal tract and hydrolyzed to glutamic acid and ethylamine in the rat kidney.     

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.     

Identification and antioxidant activity of flavonoid metabolites in plasma and urine of eriocitrin-treated rats

Eriocitrin, a flavonoid glycoside present in lemon fruit, is metabolized in vivo to a series of eriodictyol, methylated eriodictyol, 3,4-dihydroxyhydrocinnamic acid, and their conjugates. Plasma antioxidant activity increased following oral administration of aqueous eriocitrin solutions to rats. Eriocitrin metabolites were found in plasma and renal excreted urine through HPLC and LC-MS analyses. Eriocitrin was not detected in plasma and urine, but eriodictyol, homoeriodictyol, and hesperetin in their conjugated forms were detected in plasma of 4.0 h following administration of eriocitrin. In urine for 24 h, both nonconjugates and conjugates of these metabolites were detected. 3,4-Dihydroxyhydrocinnamic acid, which is metabolized from eriodictyol by intestinal bacteria, was detected in slight amounts with each form in 4.0-h plasma and 24-h urine. Eriocitrin was suggested to be metabolized by intestinal bacteria, and then eriodictyol and 3,4-dihydroxyhydrocinnamic of its metabolite were absorbed. Following administration of eriocitrin, plasma exhibited an elevated resistance effect to lipid peroxidation. Eriocitrin metabolites functioning as antioxidant agents are discussed.     

Mass spectrometric identification and high-performance liquid chromatographic determination of a flavonoid glycoside naringin in human urine

The aim of this study was to evaluate the absorption of a citrus flavonoid, naringin, as its glycosylated form. Six healthy volunteers (three males and three females) were studied. After a single oral administeration of 500 mg of naringin, intact naringin was isolated from 2-4 h urine. Isolated naringin was identified by the LC/electrospray ionization mass spectrometry (ESI-MS), MS/MS, and MS/MS/MS techniques. The cumulative urinary excretion of naringin and its metabolites (naringenin and naringenin glucuronides) was determined by HPLC for 0-24 h. Approximately 0.02% of the administered dose was recovered in urine as unchanged naringin, whereas urinary recoveries of naringenin and naringenin glucuronides were approximately 0.4 and 3.6% of the administered dose, respectively. It was concluded that trace amounts of orally administered naringin can be absorbed as the glycoside. However, it is not clear whether the glycoside is cleaved before or after absorption to generate naringenin.     

Gastrointestinal uptake of nasunin, acylated anthocyanin in eggplant

We previously showed that nasunin, acylated anthocyanins in eggplant peel, comprises two isomers, cis-nasunin and trans-nasunin. In this study, gastrointestinal absorption of cis- and trans-nasunins was studied in rats. Orally administered nasunins were quickly absorbed in their original acylated forms and maximally appeared in blood plasma after 15 min. When the maximum plasma concentration and area under the plasma concentration curve were normalized by orally administered dose (micromoles per kilogram), there was no significant difference in the uptake efficiency between two isomers and both exhibited a plasma level almost identical to that of delphinidin 3-O-beta-D-glucopyranoside. However, metabolites such as 4'-O-methyl analogues and extended glucuronides which were observed for delphinidin 3-O-beta-D-glucopyranoside and cyanidin 3-O-beta-D-glucopyranoside metabolisms were not detected in urine or blood plasma. Moreover, deacylated and glycolytic products of nasunins such as delphinidin 3-O-beta-D-glucopyranoside or delphinidin (aglycone) were also not detected in blood plasma even after oral administration for 8 h. These results indicated that nasunins were absorbed in their original acylated forms and exhibit a bioavailability almost identical to that of nonacylated anthocyanins.     

The metabolic fate of purified glucoraphanin in F344 rats

Dietary broccoli is commonly eaten cooked, exposing individuals to intact glucoraphanin rather than to its hydrolysis product, the anticarcinogenic isothiocyanate sulforaphane, since cooking destroys the hydrolyzing enzyme myrosinase. There is little information on the absorption and metabolism of glucoraphanin, due partly to the lack of purified compound. In this study, glucoraphanin was purified from broccoli seed and 150 mumol/kg was administered to male F344 rats. Glucoraphanin (5% of an oral dose) was recovered intact in urine, showing that it is absorbed intact, and no glucoraphanin or metabolites were found in feces. Total urinary products accounted for 20 and 45% of oral and intraperitonneal doses, respectively, including sulforaphane N-acetyl cysteine conjugate (12.5 and 2%), free sulforaphane (0.65 and 0.77%), sulforaphane nitrile (2 and 1.4%), and erucin (0.1 and 0.1%), respectively. Both glucoraphanin and its reduced form glucoerucin were identified in bile following intravenous glucoraphanin administration. We conclude that orally administered glucoraphanin is absorbed intact, undergoes enterohepatic circulation, and is hydrolyzed in the gut in F344 rats.     

Absorption of calcium fumarate salts is equivalent to other calcium salts when measured in the rat model

Calcium absorption from fumarate salts (calcium fumarate and calcium malate fumarate), which have recently been considered for use as sources for food and beverage enrichment, was compared to that from calcium citrate malate, calcium citrate, and calcium carbonate. Salts were instrinsically labeled with 45Ca and orally administered to Sprague-Dawley rats. Fractional absorption of calcium from each salt was determined using the femur uptake model. Fractional absorption from the five salts (0.30-0.27) was not significantly different (p > 0.05). Thus, when measured in the rat model, calcium from calcium fumarate and calcium malate fumarate is absorbed equally well as compared to other salts, which are common calcium sources in many foods, beverages, and supplements.     

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.     

Tissue iron distribution and urinary mineral excretion vary depending on the form of iron (FeSO4 or NaFeEDTA) and the route of administration (oral or subcutaneous) in rats given high doses of iron

Sodium iron ethylenediaminetetraacetate (NaFeEDTA) has considerable promise as an iron fortificant in food. However, effects of administering high levels of NaFeEDTA on tissue iron distribution and mineral excretion are not well understood. The objectives of this study were to assess nonheme iron distribution in the body and urinary excretion of Ca, Mg, Cu, Fe, and Zn after daily administration of high levels of iron to rats over 21 days. Iron was either given orally with food or injected subcutaneously, as either FeSO 4 or NaFeEDTA. Selected tissues were collected for nonheme iron analysis. Estimated total body nonheme iron levels were similar in rats fed NaFeEDTA or FeSO 4, but the tissue distribution was different: it was 53% lower in the liver and 86% higher in the kidneys among rats fed NaFeEDTA than among those fed FeSO 4. In contrast, body nonheme iron was 3.2-fold higher in rats injected with FeSO 4 than in rats injected with NaFeEDTA. Administering NaFeEDTA orally elevated urinary Cu, Fe, and Zn excretion compared with FeSO 4 (1.41-, 11.9-, and 13.9-fold higher, respectively). We conclude that iron is dissociated from the EDTA complex prior to or during intestinal absorption. A portion of intact FeEDTA may be absorbed via a paracellular route at high levels of intake but is mostly excreted in the urine. Metal-free EDTA may be absorbed and cause elevated urinary excretion of Fe, Cu, and Zn.     

Rapid determination of crocetin esters and picrocrocin from saffron spice (Crocus sativus L.) using UV-visible spectrophotometry for quality control

The aim of this work was the development of multivariate models able to determine the content of the main crocetin esters and picrocrocin from spectrophotometric data that could be used for routine quality control of saffron. These compounds were determined with HPLC in Spanish saffron, and their absorbance spectra from 190 to 700 nm were simultaneously monitored. Partial least-squares regression (PLSR) models have been obtained and applied to the determination of individual crocetin esters, to the sum of crocetin esters, and to picrocrocin. A modification of the Kennard-Stone algorithm was used to divide the pool of samples into calibration and validation subsets. The best predictions were obtained with the sum of crocetin esters model, followed by the model for cis-crocetin (beta- D-glucosyl)-(beta- D-gentiobiosyl) ester, trans-crocetin di-(beta- D-gentiobiosyl) ester, and trans-crocetin (beta- D-glucosyl)-(beta- D-gentiobiosyl) ester, whereas the worst predictions were found with the picrocrocin and trans-crocetin (beta- D-gentiobiosyl) ester models. These models may enhance quality control in saffron enterprises.     

Studies on absorption and hydrolysis of ethyl alpha-D-glucoside in rat intestine

Ethyl alpha-D-glucoside (alpha-EG) is normally contained in Sake, which has been taken by Japanese people since ancient times. In this study, the intestinal absorption of alpha-EG was investigated using rat everted intestinal sac. Furthermore, the alpha-EG hydrolytic activity in rat intestine was compared with disaccharides hydrolytic activities, and the effects of alpha-EG on disaccharides hydrolysis were examined using crude enzyme preparation from rat intestinal acetone powder. Glucose liberated from alpha-EG was detected in a serosal solution of everted rat intestinal sac, but it was only less than 4% of absorbed intact alpha-EG. alpha-EG absorption into small intestinal tissue was reduced by elimination of sodium ion from the mucosal solution or under the presence of phlorizin. The hydrolytic activity for alpha-EG was detected in crude enzyme preparation from rat intestinal acetone powder, but it showed a low value as compared to those for disaccharides. alpha-EG showed mixed type inhibition for maltose and sucrose hydrolysis, but inhibitory concentrations of alpha-EG required for 50% inhibition for the maltose and sucrose hydrolysis were higher than those of arabinose and acarbose. In conclusion, a small amount of alpha-EG was hydrolyzed and most of it was absorbed via SGLT1 as an intact form in the rat small intestine, and the inhibitory effect of alpha-EG on disaccharides hydrolysis was weak.     

Pharmacokinetic study of caffeic and rosmarinic acids in rats after oral administration

p-Coumaric and ferulic acid are actively taken up by monocarboxylic acid transporter (MCT), whereas gallic acid, caffeic acid (CA), and rosmarinic acid (RA) are absorbed by paracellular diffusion in human intestinal Caco-2 cells, although CA has low affinity for MCT. We previously demonstrated that p-coumaric acid has a much higher absorption efficiency than gallic acid in rats, owing to the MCT-mediated absorption of p-coumaric acid in vivo (J. Agric. Food Chem. 2004, 52, 2527-2532). Here, absorption of orally administered CA and RA in rats has been studied to investigate their intestinal absorption characteristics and pharmacokinetics in vivo and to compare the results with those of p-coumaric and gallic acids obtained under identical conditions. Rats were given 100 micromol/kg body weight of CA and RA, and blood was collected from the portal vein and abdominal artery after administration. CA, RA, and their metabolites were quantified by a coulometric detection method using HPLC-ECD. The serum concentration of intact CA and RA in the portal vein peaked at 10 min after administration, with a C(max) of 11.24 micromol/L for CA and 1.36 micromol/L for RA. The area under the curve (AUC) for intact CA and RA in the portal vein was calculated from the serum concentration-time profile to be 585.0 and 60.4 micromol min L-1, respectively. The absorption efficiency of CA was about 9.7-fold higher than that of RA. Overall, the absorption efficiency of these compounds in vivo increases in the order: gallic acid = RA < CA < p-coumaric acid, which is in good agreement with results obtained in Caco-2 cells in vitro.