Ferulic acid conjugates

Bokera M, Heuer S, Wray V, Witte L, Macek T, Vanek T, Strack D. Ferulic acid conjugates and betacyanins from cell cultures of Beta vulgaris. Phytochemistry 1991 30 3261-3265. 

Cereal bran and bran-enriched products are the most important source of wall-bound cinnamates with up to 30 and 7 mg ferulate/10 g in maize and wheat bran, respectively. This would make these products the richest dietary source of ferulic acid. However, coffee brew could supply up to 10 mg ferulate (as feruloylquinic acid, FQA) per 200 ml cup [13], and it is the first for conjugated ferulic acid, followed by Citrus juices. 

Healthy volunteers have shown to excrete caffeic, />-coumaric and ferulic acid in the urine after the consumption of various fruits [113]. The excretion of free ferulic acid in urine peaked after 7 h at a concentration of 7 pM after the consumption of tomatoes (36-73 g containing 21-44 mg ferulic acid). The concentration of free ferulic acid plus glucuronide (and possibly sulfate) conjugates exceeded 20 pM and accounted for some 11 -25% of the dose [ 114]. 

Figure 2.8 Summary of behavior of phenolic acid esters and free forms in the GIT and the liver. 5-O-CQA, 5-O-caffeoylquinic acid 5-O-FAAF, 5-O-feruloyl-L-arabinofura-nose C, conjugate (sulfate, glucuronide or methyl) CA, caffeic acid FA, ferulic acid FA-FA, dimer of ferulic acid FA-oligosac., ferulic acid esterified to an oligosaccharide FA-Xy, ferulic acid esterified to xylan R, alkyl group.

All these studies suggest that the metabolic pathway is the same for free and bound forms of ferulic acid. Whereas the free form is rapidly absorbed, metabolized and excreted in urine, the bound form allows a longer time period (free and conjugated) in plasma, as already suggested by the absence of free ferulic acid in rat plasma 18 h after intake from an enriched diet, whereas its metabolites were still present [Adam et al., 2002]. Even though its bioavailability, in terms of half-life in plasma and low excretion in urine, was improved when esterified, the absorption of ferulic acid from a wheat source was lower than if present as free form in a diet [Rondini et al., 2004]. This indicates that the amounts of ferulic acid circulating in plasma as well as its circulating metabolites are dependent on its form present in the food source. 

Zhao Z, Egashira Y, Sanada H. 2004. Ferulic acid is quickly absorbed from rat stomach as the free form and then conjugated mainly in liver. J Nutr 134 3083-3088. 

In search of novel natural antioxidant compounds that might posses a good brain bioavailability, our laboratory has focused attention on the phenolic compound ferulic acid ethyl ester (FAEE) (Fig. 18.1). Ferulic acid is a ubiquitous plant constituent that occurs primarily in seeds and leaves both in its free form and covalently linked to lignin and other biopolymers. Due to its phenolic nucleus and an extended side chain conjugation, it readily forms a resonance stabilized phenoxy radical that accounts for its potent antioxidant potential [Kanski et al., 2002 Kikuzaki et al., 2002], Ferulic acid has been shown to be protective against oxidative stress in vitro it is absorbed and excreted by humans, and may be a promising candidate for therapeutic intervention in AD [Yan et al., 2001]. Although ferulic acid has been demonstrated to be effective in vitro, the low lipophilicity impairs its in vivo efficiency, bioavailability, and stability. 

As the vast majority of human studies on the effects of phytosterols on serum cholesterol levels have been done using free sterols and sterol fatty acid esters, there has been a debate about the efficacy of the other natural sterol conjugates in lowering cholesterol. However, recent studies have demonstrated that other conjugates (ferulic acid... 

Of the various plant sterol conjugates, SFs are known to prevent lipid oxidation in various systems. The activity is based on the capability of ferulic acid to donate hydrogen from the phenolic hydroxyl group to a radical. The resulting SF radical formed is resonance stabilized, and the SF radicals may still effectively interfere with the chain reaction of... 

Since ferulic acid (free or bound), the precursor of PVG, contains an activated double bond conjugated to a carboxylic acid and to a phenyl ring, we hypothesized that it may also be sensitive to the nucleophilic attack by thiols, thereby inhibiting PVG formation. Pasteurized SSOJ samples (20 mL) were fortified with L-cysteine or N-acetyl-L-cysteine and stored at 45°C for 14 days (28). In addition, SSOJ samples were also stored for six weeks at 4, 15, 25 and 35°C. Extraction of PVG from the incubated SSOJ samples was performed, and samples were analyzed for PVG by HPLC. 

Hydroxycinnamates as well as their conjugates may act as powerful antioxidants. In edible plants they have received much attention as protecting agents against oxidative deterioration of food. Antioxidant mechanism studies on ferulic acid and its coupling products with linoleate on the molecular level have been conducted recently. A radical scavenging reaction occurred at the 3 -position of the ferulate radical with four types of peroxyl radicals of ethyl linoleate. The produced peroxides subsequently underwent intramolecular rearrangement to afford stable tricyclic peroxides (Masuda et al. 2006). 

Many other studies have reported the appearance of methylated products as metabolites of caffeic acid derivatives. In particular, ferulic and dihydro-ferulic acids and additionally feruloylglycine were identified as urinary metabolites of caffeic acid derivatives from a cmde extract of Equisetum arvense in a human study [20], The rate of conjugation with glucuronic acid in this study was >90% for ferulic acid, 60-80% for dihydrofemlic acid, and 16% for... 

Caffeic acid 42-96 nmoI/L, entirely as glucuronide) and ferulic (not detectable-78 nmol/L, more than 50% as free acid) were detected in plasma of three volunteers post ingestion of 100 g of prunes after a 2-day low-hydroxycinnamate diet [22]. Furthermore, two of the three volunteers displayed basal plasma levels of caffeic acid (as glucuronide) and ferulic acid (more than 50% as free acid). Conjugated and free caffeic (0.146-0.496 pmol, 36-87% as free acid), ferulic acid (0.008-0.032 pmol), and chlorogenic acid (0.019-0.045 pmol as free acid) were identified post ingestion in the urine of the three volunteers, of whom two showed basal urinary levels of the compounds. Thus, there is considerable contradictory evidence for the potential absorption of chlorogenic acid per se. 

However, the O-methylation of the catechol group seems to influence the rate of absorption of ferulic acid compared to that of caffeic acid. In rats 10.5 2.5% of an oral administered dose of 50 mg/kg was recovered in urine, approximately 50% as the free acid and the other 50% conjugated with... 

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