RED WINE PROANTHOCYANIDINS

A Summary

The term "Polyphenols" describes a number of natural compounds with a dietetically attractive effect. They have in common that they contain hydroxyphenyl groups (1). In red wine basically two types of these polyphenols occur, the non-flavonoid type on the one hand bearing hydroxy phenyl moieties predominantly as caffeic acid (2) (esterified with tartaric acid as caftaric acid) and - more important - the flavonoid type. The latter contain either flavanol (4), flavylium (5) or flavon (6) units. Examples for (4) is catechin (and the diastereomeric epicatechin), for (5) cyanidin (an anthocyanidin), for (6) quercetin.

Hydroxyphenyl residue	Caffeic acid	Gallic acid
Catechin, Epicatechin	Cyanidin: R1,R3=OH; R2=H	Quercetin
 	Malividin: R1, R2=OCH3; R3=OH	 

Origin of the non-flavonoid polyphenols of red wine is the fruit pulp of the grape berry, origin of the flavonoid polyphenols are seeds and skins of the grapes which release these compounds into the grape juice during fermentation (SINGLETON, 1992; BOURZEIX, 1986). The main quantity of the (colorless) flavanols are found in the grape seeds, the skins contain next to flavanols also the color imparting anthocyanins, that is, glucosides of anthocyanidins with a flavylium ion as basic unit. Red wine anthocyanidins are predominantly cyanidin and malvidin (4). Flavons (rutin, quercetin (5), myricetin) do also occur in red wine (FRANKEL, 1995), they are probably oxidation products of flavanols. Flavanols are the main constituents of the polyphenols found in red wine, namely catechin and (the diastereomeric) epicatechin and oligomers of the two in which the epicatechin units are frequently esterified with gallic acid (6).

(The situation with white grapes is essentially the same as with red grapes except that (color imparting) anthocyanidins are absent. White wine itself contains only non-flavonoid polyphenols as white grape must is not allowed to stay in contact with skins and seeds for any time before fermentation so that no flavonoid polyphenols can be released into the must).

Only the flavanols (not the flavons) are inclined towards oligomerization and are therefore sometimes referred to as "Pycnogenols" (Greek, meaning roughly "condensor"). The term has a more commercial rather than scientific meaning. The oligomeric flavanols are also called proanthocyanidins as the colorless substances yield colored anthocyanidins when exposed to acid and air. In case of red wine one often speaks of procyanidin as the red wine proanthocyanidins are indeed predominantly procyanidins forming thus in oxidative acidic hydrolysis specifically cyanidin. (Leuko-anthocyanidins are not identical with pro-anthocyanidins: the former are MONOmeric 3,4-flavan-DIOLS, the latter are OLIGOmeric 3-flavanOLS, both are not coloured, both form coloured anthocyanidins on oxidation).

In general one may say that the 3-flavanols: (epi-)catechin, gallo(epi)catechin, fisetinidol, robinetinidol oligomerize in plants into the proanthocyanidins: procyanidin, prodelphinidin, profisetinidin, prorobetinidin, which yield in vitro on acidic oxidative hydrolysis the corresponding anthocyanidins: cyanidin, delphinidin, fisetinidin, robetinidin. Specifically in red wine one may say that (epi)catechin oligomerizes into procyanidin, which on acidic, oxydative hydrolysis yields cyanidin (PORTER, 1992).

Pro-anthocyanidins do occur also in other plants and plant parts, for instance in bark of conifers (MASQUELIER, 1980) and in fruits (LEA, 1992). They are in low concentration important for the flavor of wine, fruits and fruit juices. Their taste depends on the degree of oligomerization. Up to a oligomerization degree of 4 (the actual pro-anthocyanidins) a bitter note predominates, at oligomerization beyond 4 the taste is astringent as in sloes and quinces (for the higher oligomers the designation tannin is also appropriate) (LEA, 1992).

Catechins und pro-anthocyanidins are very potent free radical scavengers. This is the basis of their antioxidative effect (CHENIER, 1992). The term "French paradox" refers to the observation that deaths caused by coronary heart desease are less common in France in comparison to other countries with similar dietetic habits (that is with a high consumption of saturated fatty acids). By a statistical analysis of various factors RENAUD (1992) found that the consumption of red wine must be the reason for this phenomenon. The same explanation was already suggested in 1979 by St. LEGER. Polyphenols occurring in red wine (be it of flavonoid or non-flavonoid type) inhibit the copper ion catalyzed oxidation of low density lipoproteins (LDL). This can be shown by the measurement of the hexanal which is generated as a consequence of the oxidation (FRANKEL, 1993(I)). Oxidized low density lipoproteins are essentially responsible for the atherogenesis (that is formation of plaques in the vessels (KINSELLA, 1993). The protection against oxidation conveyed by red wine (which can also be observed in vivo (MAXWELL, 1994)) is based on the scavenge of free radicals. Red wine polyphenols are in this respect more valuable than tocopherol as they show an effect at a much lower concentration (FRANKEL, 1993(II)). In order to determine which individual red wine polyphenols are responsible for the antioxidative effect FRANKEL (1995) tested 20 wine samples in vitro and determined then the concentrations of the various polyphenols in the red wine samples. A statistical analysis showed the best correlation with the total polyphenolic content of the corresponding sample and a partly good and partly inferior correlation with individual constituents. This allows to conclude that a more or less pronounced antioxidative effect is a characteristic of all red wine polyphenols. Resveratrol (a stilbene derivative) of which a particular effect was expected on account of its presence in East Asian herbal medicines does not play a significant role in red wine (FRANKEL, 1993(II)). The activity of the anthocyanidines, cyanidin and malvidin, is comparatively low, the activity of the flavon derivatives (myricetin, quercetin, rutin) was in this in-vitro experiments high, while in vivo the effect appears to be inferior to the one of the pro-anthocyanidins because of their poor absorption (MASQUELIER, 1980). An anti-tumor activity was found of the non-flavonoid polyphenols gallic, ellagic and tannic acid (PERCHELLET, 1992), of the flavonoid quercetin (the aglykon of rutin) such an activity is considered to be probable (STAVRIC, 1994).
In red wine occasionally the compound Resveratrol is found in low concentration (in the ppm range). Resveratrol is a phytoalexin, that is, a compound formed by plants in defense of fungus attacks. It therefore occurs in red wine only if the grapes had before been infected by the mould "Botrytis" ("noble rottenness") an infection desired by vintners as it destroys the grape skin and thus allows evaporation (and that is concentration) of the grape juice. Resveratrol is anticancerogenic, apparently Because it is converted into the toxic compound Piceatannol by an enzyme which occurs in cancer cells only (POTTER, 2002; WIEDER, 2001).
In certain plants Resveratrol is formed independently of fungus infections. Thus it is possible to prepare an extract from certain Polygonum species containing as much as 5% Resveratrol.

References

BOURZEIX, M. et al. 1986: Étude des catecéchines et des procyanidols de la grappe de raisin, du vin et d'autres dérivés de la vigne. Bulletin de L'O.I.V, 1986, 669-670

CHENIER, V. et al., 1992: Structure of Procyanidin Oligomers isolated from Grape Seeds in Relation to Some of their Chemical Properties, p. 281-294, in: Plant Polyphenols, ed. R. W. Hemingway, P.E. Laks, Plenum Press, 1992

FRANKEL, E.N. et al., 1993 (I): Inhibition of oxidation of human low-density lipoprotein by phenolic substances. The Lancet, 341, Feb. 20, 1993, 454-457

FRANKEL, E.N. et al., 1993 (II): Inhibition of human LDL oxidation by resveratrol. The Lancet, 341, April 24, 1993, 1103-1104

FRANKEL, E.N. et al., 1995: Principal Phenolic Phytochemicals in Selected California Wines and Their Antioxidant Activity in Inhibiting Oxidation of Human Low-Density Lipoproteins. J. Agric. Food Chem. Vol. 43, No. 4, 1995, 890-894

KINSELLA, J.E., et al.: 1993: Possible Mechanisms for the Protective Role of Antioxidants in Wine and Plant Foods. Food Technology, April 1993, 35-39

LEA, A.G.H., 1992: Flavor, Color and Stability in Fruit Products: The Effect of Polyphenols, p. 827-847, in: Plant Polyphenols, ed. R. W. Hemingway, P.E. Laks, Plenum Press, 1992

MASQUELIER, J., 1980: Pycnogenols: Recent Advances in the Therapeutical Activity of Procyanidins. In: J.L. Beal and E. Reinhard, Natural Products as Medicinal Agents

MAXWELL, S. et al., 1994: Red wine and antioxidant activity in serum. Lancet 344, 193-194

PERCHELLET, J.P. et al., 1992: Antitumor Promoting Activities of Tannic Acid, Ellagic Acid, and several Gallic Acid Derivatives in Mouse Skin, p. 783-801, in: Plant Polyphenols, ed. R. W. Hemingway, P.E. Laks, Plenum Press, 1992

PORTER, L.J., 1992: Structure and Chemical Proeprties of the Condensed Tannins, p. 245-258, in: Plant Polyphenols, ed. R. W. Hemingway, P.E. Laks, Plenum Press, 1992

POTTER, G.A. et al., 2002: The cancer preventive agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1B1. British Journal of Cancer, 86, 774-778 (04. Mar 2002)

RENAUD, S. et al., 1992: Wine, Alcohol, Platelets, and the French Paradox for Coronary Heart Desease. Lancet 1992, 339, 1523-1526 St. LEGER et al., 1979: Factors associated with cardia mortality in developed countries with particular reference to the consumption of wine. Lancet 1979, May 12, 1017-20

SINGLETON, V.L., 1992: Tannins and the Qualities of Wines, p. 859-880, in: Plant Polyphenols, ed. R. W. Hemingway, P.E. Laks, Plenum Press, 1992

STAVRIC, B., 1994: Quercetin in Our Diet: From potent Mutagen to Probable Anticarcinogen.

WIEDER, T., et al., 2001: Piceatannol, a hydroxylated analog of  the chemopreventive agent resveratrol, is a potent inducer of apoptosis in the lymphoma cell line BJAB and in primary, leukemic lymphoblasts. Leukemia, November 2001, Vol 15, No. 11 pp. 1735-1742

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