Relationships among the flavonoids

 The basic flavonoid structure originates from two sources: The 'A' ring is formed from three acetate units (via the acetate pathway) and the 'B' ring with the 3-carbon bridge is constructed of a phenylpropane unit via the shikimic acid pathway. The following illustration¹ outlines the biosynthetic relationships between the different major classes of flavonoids:

 Comparison of antioxidant flavonoids

Polyphenolic compounds have repeatedly been demonstrated, in vitro, to inhibit lipoxygenase and cyclooxygenase enzymes and lipid peroxidation, and to scavenge free radicals including hydroxyl, peroxyl, and superoxide radicals. Studies have also found both an increased antioxidant capacity of human blood plasma following ingestion of polyphenols, and a decreased level of LDL cholesterol oxidation.^2,3

Various investigations have established a relationship between the structure of different flavonoids and their relative efficiencies as antioxidants (reducing agents). Let's examine some features of various flavonoids that make them good reducing agents. Basically, these phytochemicals can donate an electron (accompanied by a hydrogen nucleus) from the -OH groups attached to their phenolic rings, to a free radical. This electron stabilizes and inactivates the damaging radical. In the process, the polyphenolic reducing agent becomes an aroxyl radical which is considerably more stable than the free radical that it has reduced; the result is the cessation of damaging oxidative chain reactions. Some evidence indicates that vitamin C (ascorbate) and glutathione work synergistically with polyphenols, regenerating them through replacing their lost hydrogen atoms.⁴

One factor that influences the antioxidant capacity of a flavonoid is the degree of hydroxylation on the 'B' ring. In the structures below, we see a progression in the reducing abilities of three flavone compounds as the degree of hydroxylation increases*:

You can also observe this trend when comparing the anthocyanidins Pelargonidin, Cyanidin and Delphinidin:

Even higher antioxidant values are demonstrated by the flavanols Epigallocatechin, Epicatechin gallate, and Epigallocatechin gallate, as they exhibit increasing degrees of overall hydroxylation:

All of this information is relevant, but it should be remembered that in vitro results obtained using isolated compounds are not directly equivalent to "real-life" situations. The activity of an antioxidant compound may be influenced by other compounds with which it occurs (such as ascorbate); it may also be modified by the enzymatic and microbial environment of the individual human digestive system. In some cases, metabolites may be even more active than the parent compounds.

1. Adapted from Comprehensive Natural Products Chemistry; Barton; Nakanishi; Cohn Eds. Vol. 1. Elsevier: Amsterdam, 1999; p 716.
2. Serafini, M.; Maiani, G.; Ferro-Luzzi, A. Journal of Nutrition 1998 128: 1003-7.
3. Serafini, M. et al.  Journal of Nutrition 2000 11: 585-90.
4. Skaper, S.D. et al. Free Radical Biology and Medicine 1997 22: 669-78.
5. Pannala, A. S.; Rice-Evans, C. In: Flavonoids and Other Polyphenols (Methods in Enzymology Vol. 335); Packer, L. Ed. Academic Press: San Diego, 2001; p 266-72.
6. Bors, W.; Michel, C.; Stettmaier, K. In: Flavonoids and Other Polyphenols (Methods in Enzymology Vol. 335); Packer, L. Ed. Academic Press: San Diego, 2001; p 166-180.