Proanthocyanidins are oligomeric and polymeric end products of the flavonoid biosynthetic pathway. They are present in the fruits, bark, leaves and seeds of many plants, where they provide protection against predation. At the same time they give flavor and astringency to beverages such as wine, fruit juices and teas, and are increasingly recognized as having beneficial effects on human health. The presence of proanthocyanidins is also a major quality factor for forage crops. The past 2 years have seen important breakthroughs in our understanding of the biosynthesis of the building blocks of proanthocyanidins, the flavan-3-ols (+)-catechin and (-)-epicatechin. However, virtually nothing is known about the ways in which these units are assembled into the corresponding oligomers in vivo. Molecular genetic approaches are leading to an understanding of the regulatory genes that control proanthocyanidin biosynthesis, and this information, together with increased knowledge of the enzymes specific for the pathway, will facilitate the genetic engineering of plants for introduction of value-added nutraceutical and forage quality traits.

/pdf/proanthocyanidins-a-final-frontier-in-flavonoid-research-2d9bo57ypm.pdf

Proanthocyanidins--a final frontier in flavonoid research?

Objective The increasing prevalence of obesity and type 2 diabetes (T2D) demonstrates the failure of conventional treatments to curb these diseases. The gut microbiota has been put forward as a key player in the pathophysiology of diet-induced T2D. Importantly, cranberry ( Vaccinium macrocarpon Aiton) is associated with a number of beneficial health effects. We aimed to investigate the metabolic impact of a cranberry extract (CE) on high fat/high sucrose (HFHS)-fed mice and to determine whether its consequent antidiabetic effects are related to modulations in the gut microbiota. Design C57BL/6J mice were fed either a chow or a HFHS diet. HFHS-fed mice were gavaged daily either with vehicle (water) or CE (200 mg/kg) for 8 weeks. The composition of the gut microbiota was assessed by analysing 16S rRNA gene sequences with 454 pyrosequencing. Results CE treatment was found to reduce HFHS-induced weight gain and visceral obesity. CE treatment also decreased liver weight and triglyceride accumulation in association with blunted hepatic oxidative stress and inflammation. CE administration improved insulin sensitivity, as revealed by improved insulin tolerance, lower homeostasis model assessment of insulin resistance and decreased glucose-induced hyperinsulinaemia during an oral glucose tolerance test. CE treatment was found to lower intestinal triglyceride content and to alleviate intestinal inflammation and oxidative stress. Interestingly, CE treatment markedly increased the proportion of the mucin-degrading bacterium Akkermansia in our metagenomic samples. Conclusions CE exerts beneficial metabolic effects through improving HFHS diet-induced features of the metabolic syndrome, which is associated with a proportional increase in Akkermansia spp. population.

https://gut.bmj.com/content/gutjnl/64/6/872.full.pdf

A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice

This paper examines the nutritional and veterinary effects of tannins on ruminants and makes some comparisons with non-ruminants. Tannin chemistry per se is not covered and readers are referred to several excellent reviews instead: (a) Okuda T et al. Heterocycles 30:1195-1218 (1990); (b) Ferreira D and Slade D. Nat Prod Rep 19:517-541 (2002); (c) Yoshida T et al. In Studies in Natural Product Chemistry. Elsevier Science, Amsterdam, pp. 395-453 (2000); (d) Khanbabaee K and van Ree T. Nat Prod Rep 18:641-649 (2001); (e) Okuda et al. Phytochemistvy 55:513-529 (2000). The effects of tannins on rumen micro-organisms are also not reviewed, as these have been addressed by others: (a) McSweeney CS et al. Anim Feed Sci Technol 91:83-93 (2001); (b) Smith AH and Mackie RI. Appl Environ Microbiol 70:1104-1115 (2004). This paper deals first with the nutritional effects of tannins in animal feeds, their qualitative and quantitative diversity, and the implications of tannin-protein complexation. It then summarises the known physiological and harmful effects and discusses the equivocal evidence of the bioavailability of tannins. Issues concerning tannin metabolism and systemic effects are also considered. Opportunities are presented on how to treat feeds with high tannin contents, and some lesser-known but successful feeding strategies are highlighted. Recent research has explored the use of tannins for preventing animal deaths from bloat, for reducing intestinal parasites and for lowering gaseous ammonia and methane emissions. Finally, several tannin assays and a hypothesis are discussed that merit further investigation in order to assess their suitability for predicting animal responses. The aim is to provoke discussion and spur readers into new approaches. An attempt is made to synthesise the emerging information for relating tannin structures with their activities. Although many plants with high levels of tannins produce negative effects and require treatments, others are very useful animal feeds. Our ability to predict whether tannin-containing feeds confer positive or negative effects will depend on interdisciplinary research between animal nutritionists and plant chemists. The elucidation of tannin structure-activity relationships presents exciting opportunities for future feeding strategies that will benefit ruminants and the environment within the contexts of extensive, semi-intensive and some intensive agricultural systems. (c) 2006 Society of Chemical Industry

Unravelling the conundrum of tannins in animal nutrition and health

Flavonoids and their polymers constitute a large class of food constituents, many of which alter metabolic processes and have a positive impact on health. Flavonoids are a subclass of polyphenols. They generally consist of two aromatic rings, each containing at least one hydroxyl, which are connected through a three-carbon "bridge" and become part of a six-member heterocyclic ring. The flavonoids are further divided into subclasses based on the connection of an aromatic ring to the heterocyclic ring, as well as the oxidation state and functional groups of the heterocyclic ring. Within each subclass, individual compounds are characterized by specific hydroxylation and conjugation patterns. Many flavonoids in foods also occur as large molecules (tannins). These include condensed tannins (proanthocyanidins), derived tannins and hydrolysable tannins. For proanthocyanidins, three subclasses (15 characterized) have been identified in foods. Monomers are connected through specific carbon-carbon and ether linkages to form polymers. Derived tannins are formed during food handling and processing, and found primarily in black and oolong teas. Flavonoids are widely distributed in nature, albeit not uniformly. As a result, specific groups of foods are often rich sources of one or more subclasses of these polyphenols. The polyphenolic structure of flavonoids and tannins renders them quite sensitive to oxidative enzymes and cooking conditions. Scientists in several countries have estimated intakes of a few subclasses of flavonoids from limited food composition databases. These observations suggest large differences in consumption, due in part to cultural and food preferences among populations of each country.

Overview of Dietary Flavonoids: Nomenclature, Occurrence and Intake

http://users.atw.hu/koles/koles/eload/kiss/Sorghum_and_millet_phenols_and_antioxidants_(2006).pdf

Sorghum and millet phenols and antioxidants

Three proanthocyanidin trimers possessing A-type interflavanoid linkages, epicatechin-(4β→6)-epicatechin-(4β→8, 2β→O→7)-epicatechin (4), epicatechin-(4β→8, 2β→O→7)-epicatechin-(4β→8)-epicatechin (5), and epicatechin-(4β→8)-epicatechin-(4β→8, 2β→O→7)-epicatechin (6), were isolated from the ripe fruits of Vaccinium macrocarpon (cranberry) and prevented adherence of P-fimbriated Escherichia coli isolates from the urinary tract to cellular surfaces containing α-Gal(1→4)β-Gal receptor sequences similar to those on uroepithelial cells. The structure of 4 was elucidated by a combination of spectroscopic methods and acid-catalyzed degradation with phloroglucinol. Also isolated were the weakly active epicatechin-(4β→8, 2β→O→7)-epicatechin (procyanidin A2) (3) and the inactive monomer epicatechin (1) and the inactive dimer epicatechin-(4β→8)-epicatechin (procyanidin B2) (2).

Yinrong Lu

Papers

A-Type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli.

The structure of cranberry proanthocyanidins which inhibit adherence of uropathogenic P-fimbriated Escherichia coli in vitro.

Structure and Genetic Variation of Cranberry Proanthocyanidins That Inhibit Adherence of Uropathogenic P-FimbriatedE. coli