Ferulic acid (FA) is one of the most abundant phenolic antioxidants in the human diet. Many studies have documented its beneficial properties. It is therefore essential to understand the absorption and metabolism of FA in detail. The purpose of this study was to confirm the hypothesis that FA is absorbed in rat stomach and metabolized mainly in the liver. We determined the recovery of FA and its metabolites (FA sulfate/glucuronides) in rat gastric contents, gastric mucosa, portal vein plasma, celiac arterial plasma, bile, and urine after 2.25 micromol FA was administered in 0.5 mL physiological saline and incubated for 25 min in situ in the stomach of rats. Within 25 min, 74 +/- 11% of the administered FA disappeared from the stomach; later, FA was recovered in both free and conjugated forms in plasma, bile, and urine. On the other hand, only free FA was detected in the gastric contents and mucosa; it was also detected in the portal vein plasma as 49 +/- 5% of the total FA (all forms of FA). However, the proportion of free FA in the celiac arterial plasma, bile, and urine decreased to 5-8%. These results indicate that FA can be quickly absorbed from the rat stomach, and then is likely metabolized mainly in the liver. Such novel information would be helpful in the use of FA as a nutrient supplement. For example, oral administration of FA in capsule form or in a form bonded with sugar esters may provide a more appropriate concentration of FA in the circulation, which may improve its proposed efficacy in preventing chronic disease.
Ferulic acid sugar esters, the common form of ferulic acid (FA) in cereals, show a stronger antioxidant potential than FA in vitro. However, there is little information on their metabolism and excretion in vivo. In the present study, we investigated the metabolic derivatives of FA in the plasma, urine and feces of rats administered 70 micro mol/kg body of 5-O-feruloyl-L-arabinofuranose (FAA), feruloyl-arabinoxylan (FAXn) or the same molar amount of FA as a comparison. Administered FA and its sugar esters were recovered in rat plasma and urine in the form of free FA, FA-glucuronide, FA-sulfate and FA-sulfoglucuronide (FA-diconjugate with sulfate and glucuronide). The recovery of administered FA in urine was 72%, which was higher than that of administered FAA (54%) or FAXn (20%). Free FA and its derivatives were not recovered in rat feces after FA or FAA administration, but 20% of the administered FA moiety was recovered when FAXn was administered. Moreover, administered FA, in contrast to FA esters, was present in plasma in the free and conjugated forms at a higher concentration but for a shorter time. These results indicated that bioavailability of FA and its sugar esters is dependent on the absence or presence of the saccharide moiety and, in the latter case, its structure. This is the first study to show that FA-sulfoglucuronide is the main metabolite (60-70% of the total) in the plasma of rats administered FA or its sugar esters. Thus, the physiological functions of FA and its sugar esters found in vitro might require reconsideration in vivo.
We estimated the absorption site and absorptivity of ferulic acid (FA) and its sugar esters, namely 5-O-feruloyl-l-arabinofuranose (FAA) and feruloyl-arabinoxylan (FAXn), in rats on the basis of their recovery in intestinal content and feces by comparing the values with those of a nonabsorbable marker, poly R-478. The results indicated that free FA was absorbed almost completely before reaching cecum. About 40% of dietary FAA was absorbed in rat foregut and 57% disappeared in the cecum. In contrast, about 67% of the FA moiety in FAXn was released and then disappeared predominantly in the hindgut. These results suggested that the existing form of FA in diets affects its absorptivity, its absorption site, and its ensuing fate in the gastrointestinal tract. Those ingested FAs esterified with saccharides; especially, polysaccharides have to transit the hindgut where FA might be released and then absorbed and/or degraded by microflora in lumen. Such microbial degradation may be an important factor affecting the bioavailability of dietary FA.
Dietary ferulic acid (FA), a significant antioxidant substance, is currently the subject of extensive research. FA in cereals exists mainly as feruloylated sugar ester. To release FA from food matrices, it is necessary to cleave ester cross-linking by feruloyl esterase (FAE) (hydroxycinnamoyl esterase; EC 3.1.1.73). In the present study, the FAE from a human typical intestinal bacterium, Lactobacillus acidophilus, was isolated, purified, and characterized for the first time. The enzyme was purified in successive steps including hydrophobic interaction chromatography and anion-exchange chromatography. The purified FAE appeared as a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with an apparent molecular mass of 36 kDa. It has optimum pH and temperature characteristics (5.6 and 37°C, respectively). Ferulic acid (FA) is a common component in plant cell walls and shows strong antioxidant potential by its radical-scavenging ability (16). In recent years, the results of many in vitro and in vivo studies have indicated that FA prevents low-density lipoprotein from oxidation (2, 27, 29, 31), exhibits inhibitory effects on tumor promotion (1, 17), and protects against certain chronic diseases such as coronary heart disease and some cancers (6,20,21,37).In cereals, FA is mainly ester linked with arabinose or galactose residues (which constitute side chains of cell wall polysaccharides) (15,18,19,28,34,38). Wende et al. showed that FA was released from 2-O--D-xylopyranosyl-(5-O-feruloyl)-Larabinose by rat gut microorganisms quite quickly and presumed that feruloyl esterase (FAE) would be produced by microorganisms, with high-level activity which is closely related to the release (40). Subsequently, other in vitro observations confirmed the existence of FAE in animal and human intestines (3, 23). These results suggest that FAE plays an important role in releasing free FA from different feruloylated forms in foodstuff in the gut.Although FAEs from some eukaryotic cells (4,7,11,12,14,22,26,39) and from only one prokaryotic cell (13) have been purified and characterized to date, there is no information about FAE from intestinal bacteria. It is reported that FAEs from various sources show different properties with respect to such characteristics as optimal temperature and optimal pH. Therefore, it is necessary to purify the FAE from human gut bacteria to further study the mechanism of release of FA from complex food matrices in vitro. Nishizawa et al. studied the FAE activities of typical intestinal bacteria and found that among the intestinal bacteria tested, Lactobacillus acidophilus exhibited the highest level of activity with respect to feruloylated arabinose ester (30).Some investigations indicate that the presence of xylanase enhances FAE activity. In most of these studies, however, destarched wheat bran was used as a substrate; these experiments could not supply sufficiently detailed information to explain the releasing mechanism of dietary FA and the interaction between xylanase and FAE to ...
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