Flavonoid metabolites

Figure 2. Photograph of an autoradiogram of the chromatographed leaves administered [14C]cinnamate for 10 min. Compounds I to VI (Figure 1) are the final flavonoid metabolites which accumulate in this tissue.

Pietta, P.G. et al.. Identification of flavonoid metabolites after oral administration to rats of a Ginkgo biloba extract, J. Chromatogr. B — Biomed. Appl, 673, 75, 1995. 

Mullen W, Boitier A, Stewart AJ, Crozier A. 2004. Flavonoid metabolites in human plasma and urine after the consumption of red onions Analysis by liquid chromatography with photodiode array and full scan tandem mass spectrometric detection. J Chromatogr A 1058 163-168. 

Pollard SE, Kuhnle GG, Vauzour D, Vafeiadou K, Tzounis X, Whiteman M, Rice-Evans C, Spencer JP. 2006. The reaction of flavonoid metabolites with peroxynitrite. Biochem Biophys Res Commun 350 960-968. 

This biotransformation is common to many xenobiotics and diminishes the potential toxicity of the substrate and facilitates its biliary and urinary elimination by increasing its hydrophilicity. Flavonoid metabolites are transported to extrahe-patic tissues and eventually to the kidneys, where they are excreted in the urine or incorporated into bile and excreted in feces.13 Because phase II metabolism is highly efficient with respect to the flavonoids, aglycones (except for anthocyanins)... 

M22. Miyake, Y., Shimoi, K., Kumazawa, S., Yamamoto, K., Kinae, N., and Osawa, T., Identification and antioxidant activity of flavonoid metabolites in plasma and urine of eriocitrin-treated rats. 

Liebgott, T. Miollan, M. Berchadsky, Y. Drieu, K. Culcasi, M. Pietri, S. Complementary cardioprotective effects of flavonoid metabolites and terpenoid constituents of Ginkgo biloba extract (EGb 761) during ischemia and reperfusion. Basic Res. Cardiol, 2000, 95 368-377. 

The information about absorption, metabolism and excretion of individual flavonoids in humans is scarce (Cook and Samman, 1996). The flavonoids are absorbed from the intestinal tracts of humans and animals and are excreted either unchanged or as flavonoid metabolites in the urine or feces. Most studies have dealt with the absorption of flavonoids after oral administration of pharmacological doses of individual flavonoids rather than dietary levels of the flavonoids. Furthermore, most experiments have been conducted using flavonoids without glycosidic substitution rather than the glycosylated flavonoids, which predominate in plants. 

Isoflavans, such as (90), represent the most reduced structures of isoflavonoids about 51 stiuctures have been reported (Dewick, 1988 Williams and Harbome, 1989b). The animal flavonoid metabolite, equol (91), is a representative of this class of compounds. Equol is formed in animals from the metabolism of compounds such as formononetin (82). Other isoflavans are known to occur in plants for example, (- )-5 -methoxysativan is found in alfalfa foliage (Fig. 11.29) (Dewick, 1982 Miller et al., 1989). 

Flavonoid aglycones that reach the large bowel are subject to ring fission by intestinal bacteria, a process in which the middle (non-aromatic) carbon ring is split apart into smaller fission metabolites. These metabolites are readily absorbed and some are known to possess therapeutic benefits in their own right (Bone 1997). Due to the process of enterohepatic circulation, the therapeutic benefits of flavonoid metabolites are sustained over a relatively long duration. 

Nonredox mechanism of actions of flavonoids might also be relevant in vivo. It has been suggested that flavonoids metabolites could interact with cell signaling cascades, influence the cell at a transcriptional level, or downregulate pathways leading to apoptosis [102]. 

The purpose of this chapter is to review different methods to investigate flavonoids and their in vivo metabolites using mass spectrometry (MS). In particular, the focus is the elucidation of the structure of in vivo flavonoid metabolite forms. Table 1 shows the structure and m/z values for the compounds described in this chapter. 

Table 4 Molecular Ion and Major Fragments (Intensity> 10%) and Their Intensities (Percentage of the Intensity of the Most Abundant Signal) of Flavonoid Metabolites, Acquired by Direct Infusion by Using Electrospray Mass Spectrometry and Low-Energy Collision-Induced Dissociation... 

The classical hydrogen-donating antioxidant properties of flavonoids, which are often used as a possible explanation for their biological activity, may, after all, not be the most important determinant for their effects in vivo. This conclusion is tenable when faetors sueh as in vivo metaboUsm and the achieved plasma and tissue coneentrations of flavonoids/metabolites are taken into account. Therefore, the bioaetivity of flavonoids in vivo may rather be supported by their ability to modulate protein fimctions, intracellular cell signaling, and receptor activities on the basis of interactions, for example, with ATP-binding sites and benzodiazepine-binding domains. 

It is flie action of these flavonoid metabolites, in particular the O-methylated flavonoids deriving from small intestinal absorption, that is of great current interest For example, the ability of 3 -0-methyl epicatechin and epicatechin glucuronides to protect against apoptotic cell death induced by... 

Flavonoid metabolites identified in vivo and their biological activities... 

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