Proanthocyanidins were discovered in 1947 by Jacques Masquelier, who developed and patented techniques for the extraction of oligomeric proanthocyanidins from pine bark andgrape seeds.[1] Proanthocyanidins are under preliminary research for the potential to reduce the risk ofurinary tract infections (UTIs) by consuming cranberries, grape seeds orred wine.[2][3]
Proanthocyanidins, including the lesser bioactive and bioavailable polymers (four or more catechins), represent a group of condensed flavan-3-ols, such asprocyanidins, prodelphinidins and propelargonidins. They can be found in many plants, most notablyapples,maritime pine bark and that of most other pine species,cinnamon,[4]aronia fruit,cocoa beans, grape seed, grape skin (procyanidins andprodelphinidins),[5] andred wines ofVitis vinifera (the European wine grape). However,bilberry,cranberry,black currant,green tea,black tea, and other plants also contain these flavonoids. Cocoa beans contain the highest concentrations.[6] Proanthocyanidins also may be isolated fromQuercus petraea andQ. robur heartwood (wine barreloaks).[7]Açaí oil, obtained from the fruit of the açaí palm (Euterpe oleracea), is rich in numerous procyanidin oligomers.[8]
Apples contain on average per serving about eight times the amount of proanthocyanidin found in wine, with some of the highest amounts found in theRed Delicious andGranny Smith varieties.[9]
An extract ofmaritime pine bark calledPycnogenol bears 65–75 percent proanthocyanidins (procyanidins).[10] Thus a 100 mg serving would contain 65 to 75 mg of proanthocyanidins (procyanidins).
DMACA is a dye that is particularly useful for localization of proanthocyanidin compounds in plant histology. The use of the reagent results in blue staining.[17] It can also be used to titrate proanthocyanidins.
Proanthocyanidins can be titrated using theProcyanidolic Index (also called theBates-Smith Assay). It is a testing method that measures the change in color when the product is mixed with certain chemicals. The greater the color changes, the higher the PCOs content is. However, the Procyanidolic Index is a relative value that can measure well over 100. Unfortunately, a Procyanidolic Index of 95 was erroneously taken to mean 95% PCO by some and began appearing on the labels of finished products. All current methods of analysis suggest that the actual PCO content of these products is much lower than 95%.[20][unreliable medical source?]
Oligomeric proanthocyanidins (OPC) strictly refer todimer andtrimerpolymerizations of catechins. OPCs are found in most plants and thus are common in the human diet. Especially theskin, seeds, andseed coats of purple or red pigmented plants contain large amounts of OPCs.[6] They are dense in grape seeds and skin, and therefore in red wine and grape seed extract, cocoa, nuts and allPrunus fruits (most concentrated in the skin), and in the bark ofCinnamomum (cinnamon)[4] andPinus pinaster (pine bark; formerly known asPinus maritima), along with many other pine species. OPCs also can be found inblueberries,cranberries (notablyprocyanidin A2),[26]aronia,[27]hawthorn,rosehip, andsea buckthorn.[28]
Proanthocyanidin has low bioavailability, with 90% remaining unabsorbed from the intestines until metabolized bygut flora to the more bioavailable metabolites.[16]
These techniques are generally calleddepolymerisation and give information such asaverage degree of polymerisation or percentage of galloylation. These areSN1 reactions, a type of substitution reaction inorganic chemistry, involving acarbocation intermediate under strongly acidic conditions in polarprotic solvents like methanol. The reaction leads to the formation of free and derived monomers that can be further analyzed or used to enhance procyanidinabsorption andbioavailability.[32] The free monomers correspond to the terminal units of the condensed tannins chains.
In general, reactions are made in methanol, especially thiolysis, as benzyl mercaptan has a low solubility in water. They involve a moderate (50 to 90 °C) heating for a few minutes.Epimerisation may happen.
Phloroglucinolysis can be used for instance for proanthocyanidins characterisation in wine or in grape seeds and skin.[33]
Cranberries have A2-type proanthocyanidins (PACs) which may be important for the ability of PACs to bind to proteins, such as theadhesins present onE. colifimbriae and were thought to inhibit bacterial infections, such asurinary tract infections (UTIs).[39]Clinical trials have produced mixed results when asking the question to confirm that PACs, particularly from cranberries, were an alternative to antibiotic prophylaxis for UTIs: 1) a 2014 scientific opinion by theEuropean Food Safety Authority rejectedphysiological evidence that cranberry PACs have a role in inhibiting bacterial pathogens involved in UTIs;[2] 2) an updated 2023Cochrane Collaboration review supported the use of cranberry products for the prevention of UTIs for certain groups.[3]
A 2017systematic review concluded that cranberry products significantly reduced the incidence of UTIs, indicating that cranberry products may be effective particularly for individuals with recurrent infections.[40] In 2019, theAmerican Urological Association released guidelines stating that a moderate level of evidence supports the use of cranberry products containing PACs for possible prevention from recurrent UTIs.[41]
Proanthocyanidins are the principal polyphenols in red wine that are under research to assess risk ofcoronary heart disease and lower overall mortality.[42] Withtannins, they also influence the aroma, flavor,mouth-feel andastringency of red wines.[43][44]
In red wines, total OPC content, includingflavan-3-ols (catechins), was substantially higher (177 mg/L) than that in white wines (9 mg/L).[45]
Proanthocyanidins found in the proprietary extract ofmaritime pine bark calledPycnogenol were not found (in 2012) to be effective as a treatment for any disease:
"Current evidence is insufficient to support Pycnogenol(®) use for the treatment of any chronic disorder. Well-designed, adequately powered trials are needed to establish the value of this treatment."[46]
Proanthocyanidins are present in fresh grapes, juice,red wine, and other darkly pigmented fruits such ascranberry,blackcurrant,elderberry, andaronia.[47] Although red wine may contain more proanthocyanidins by mass per unit of volume than does red grape juice, red grape juice contains more proanthocyanidins per average serving size. An eight US fluid ounces (240 ml) serving of grape juice averages 124 milligrams proanthocyanidins, whereas a five US fluid ounces (150 ml) serving of red wine averages 91 milligrams (i.e., 145.6 milligrams per 8 fl. oz. or 240 mL).[6] Many other foods and beverages may also contain proanthocyanidins, but few attain the levels found in red grape seeds and skins,[6] with a notable exception beingaronia, which has the highest recorded level of proanthocyanidins among fruits assessed to date (664 milligrams per 100 g).[47]
^abMateos-Martín ML, Fuguet E, Quero C, et al. (2012). "New identification of proanthocyanidins in cinnamon (Cinnamomum zeylanicum L.) using MALDI-TOF/TOF mass spectrometry".Analytical and Bioanalytical Chemistry.402 (3):1327–1336.doi:10.1007/s00216-011-5557-3.hdl:10261/88579.PMID22101466.S2CID23120410.
^Rohdewald, P (2002). "A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology".International Journal of Clinical Pharmacology and Therapeutics.40 (4):158–168.doi:10.5414/cpp40158.PMID11996210.
^Hatano, T; Miyatake, H; Natsume, M; Osakabe, N; Takizawa, T; Ito, H; Yoshida, T (2002). "Proanthocyanidin glycosides and related polyphenols from cacao liquor and their antioxidant effects".Phytochemistry.59 (7):749–758.Bibcode:2002PChem..59..749H.doi:10.1016/S0031-9422(02)00051-1.PMID11909632.
^Merghem, R.; Jay, M.; Brun, N.; Voirin, B. (2004). "Qualitative analysis and HPLC isolation and identification of procyanidins fromvicia faba".Phytochemical Analysis.15 (2):95–99.Bibcode:2004PChAn..15...95M.doi:10.1002/pca.731.PMID15116939.
^Griffiths, D. W. (1981). "The polyphenolic content and enzyme inhibitory activity of testas from bean (Vicia faba) and pea (Pisum spp.) varieties".Journal of the Science of Food and Agriculture.32 (8):797–804.Bibcode:1981JSFA...32..797G.doi:10.1002/jsfa.2740320808.
^Cabrera, A.; Martin, A. (2009). "Genetics of tannin content and its relationship with flower and testa colours in Vicia faba".The Journal of Agricultural Science.113:93–98.doi:10.1017/S0021859600084665.S2CID84456901.
^Stringano, E; Gea, A; Salminen, J. P.; Mueller-Harvey, I (2011). "Simple solution for a complex problem: Proanthocyanidins, galloyl glucoses and ellagitannins fit on a single calibration curve in high performance-gel permeation chromatography".Journal of Chromatography A.1218 (43):7804–7812.doi:10.1016/j.chroma.2011.08.082.PMID21930278.
^Engström, M. T.; Pälijärvi, M; Fryganas, C; Grabber, J. H.; Mueller-Harvey, I; Salminen, J. P. (2014). "Rapid Qualitative and Quantitative Analyses of Proanthocyanidin Oligomers and Polymers by UPLC-MS/MS".Journal of Agricultural and Food Chemistry.62 (15):3390–3399.doi:10.1021/jf500745y.PMID24665824.
^Torres, J. L.; Lozano, C. (2001). "Chromatographic characterization of proanthocyanidins after thiolysis with cysteamine".Chromatographia.54 (7–8):523–526.doi:10.1007/BF02491211.S2CID95355684.
^Jorgensen, Emily M.; Marin, Anna B.; Kennedy, James A. (2004). "Analysis of the Oxidative Degradation of Proanthocyanidins under Basic Conditions".Journal of Agricultural and Food Chemistry.52 (8):2292–2296.doi:10.1021/jf035311i.PMID15080635.
^Li, Hui-Jing; Deinzer, Max L (2007). "Tandem mass spectrometry for sequencing proanthocyanidins".Analytical Chemistry.79 (4):1739–1748.doi:10.1021/ac061823v.PMID17297981.INIST18534021.
^Carpenter JL, Caruso FL, Tata A, Vorsa N, Neto CC (2014). "Variation in proanthocyanidin content and composition among commonly grown North American cranberry cultivars (Vaccinium macrocarpon)".J Sci Food Agric.94 (13):2738–2745.Bibcode:2014JSFA...94.2738C.doi:10.1002/jsfa.6618.PMID24532348.
^Taheri, Rod; Connolly, Bryan A.; Brand, Mark H.; Bolling, Bradley W. (2013). "Underutilized Chokeberry (Aronia melanocarpa, Aronia arbutifolia, Aronia prunifolia) Accessions Are Rich Sources of Anthocyanins, Flavonoids, Hydroxycinnamic Acids, and Proanthocyanidins".Journal of Agricultural and Food Chemistry.61 (36):8581–8588.doi:10.1021/jf402449q.PMID23941506.
^Rösch, Daniel R.; Mügge, Clemens; Fogliano, Vincenzo; Kroh, Lothar W. (2004). "Antioxidant Oligomeric Proanthocyanidins from Sea Buckthorn (Hippophaë rhamnoides) Pomace".Journal of Agricultural and Food Chemistry.52 (22):6712–6718.doi:10.1021/jf040241g.PMID15506806.
^Kandil, F. E.; Song, L.; Pezzuto, J. M.; Marley, K.; Seigler, D. S.; Smith, M. A. L. (2000). "Isolation of oligomeric proanthocyanidins from flavonoid-producing cell cultures".In Vitro Cellular & Developmental Biology - Plant.36 (6):492–500.doi:10.1007/s11627-000-0088-1.S2CID25781920.
^Matthews, S.; Mila, I.; Scalbert, A.; Pollet, B.; Lapierre, C.; Hervé Du Penhoat, C. L. M.; Rolando, C.; Donnelly, D. M. X. (1997). "Method for Estimation of Proanthocyanidins Based on Their Acid Depolymerization in the Presence of Nucleophiles".Journal of Agricultural and Food Chemistry.45 (4):1195–1201.doi:10.1021/jf9607573.
^abLiu, H; Zou, T; Gao, J. M.; Gu, L (2013). "Depolymerization of cranberry procyanidins using (+)-catechin, (-)-epicatechin, and (-)-epigallocatechin gallate as chain breakers".Food Chemistry.141 (1):488–494.doi:10.1016/j.foodchem.2013.03.003.PMID23768384.
^Kennedy, J. A.; Jones, G. P. (2001). "Analysis of Proanthocyanidin Cleavage Products Following Acid-Catalysis in the Presence of Excess Phloroglucinol".Journal of Agricultural and Food Chemistry.49 (4):1740–1746.doi:10.1021/jf001030o.PMID11308320.
^Sears, K. D.; Casebier, R. L. (1968). "Cleavage of proanthocyanidins with thioglycollic acid".Chemical Communications (22): 1437.doi:10.1039/C19680001437.
^Vernhet, A.; Dubascoux, S. P.; Cabane, B.; Fulcrand, H. L. N.; Dubreucq, E.; Poncet-Legrand, C. L. (2011). "Characterization of oxidized tannins: Comparison of depolymerization methods, asymmetric flow field-flow fractionation and small-angle X-ray scattering".Analytical and Bioanalytical Chemistry.401 (5):1559–1569.doi:10.1007/s00216-011-5076-2.PMID21573842.S2CID4645218.,Vernhet, A.; Dubascoux, S. P.; Cabane, B.; Fulcrand, H. L. N.; Dubreucq, E.; Poncet-Legrand, C. L. (2011). "Characterization of oxidized tannins: Comparison of depolymerization methods, asymmetric flow field-flow fractionation and small-angle X-ray scattering".Analytical and Bioanalytical Chemistry.401 (5):1559–1569.doi:10.1007/s00216-011-5076-2.PMID21573842.S2CID4645218.
^Howell, AB (2007). "Bioactive compounds in cranberries and their role in prevention or urinary tract infections".Mol Nutr Food Res.51 (6):732–737.doi:10.1002/mnfr.200700038.PMID17487930.
^Luís, Â; Domingues, F; Pereira, L (10 March 2017). "Can Cranberries Contribute to Reduce the Incidence of Urinary Tract Infections? A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Clinical Trials".Journal of Urology.198 (3):614–621.doi:10.1016/j.juro.2017.03.078.PMID28288837.S2CID206632675.
^Absalon, C; Fabre, S; Tarascou, I; Fouquet, E; Pianet, I (2011). "New strategies to study the chemical nature of wine oligomeric procyanidins".Analytical and Bioanalytical Chemistry.401 (5):1485–1495.doi:10.1007/s00216-011-4988-1.PMID21573848.S2CID8145537.
^Gonzalo-Diago, A; Dizy, M; Fernández-Zurbano, P (2013). "Taste and mouthfeel properties of red wines proanthocyanidins and their relation to the chemical composition".Journal of Agricultural and Food Chemistry.61 (37):8861–8870.doi:10.1021/jf401041q.hdl:10261/144130.PMID23889258.
^Sánchez-Moreno, Concepción; Cao, Guohua; Ou, Boxin; Prior, Ronald L. (2003). "Anthocyanin and Proanthocyanidin Content in Selected White and Red Wines. Oxygen Radical Absorbance Capacity Comparison with Nontraditional Wines Obtained from Highbush Blueberry".Journal of Agricultural and Food Chemistry.51 (17):4889–4896.doi:10.1021/jf030081t.PMID12903941.
^abWu X, Gu L, Prior RL, McKay S (2004). "Characterization of anthocyanins and proanthocyanidins in some cultivars of Ribes, Aronia, and Sambucus and their antioxidant capacity".Journal of Agricultural and Food Chemistry.52 (26):7846–7856.doi:10.1021/jf0486850.PMID15612766.
