Polyphenols are the most abundant antioxidants in the diet and are widespread constituents of fruits, vegetables, cereals, dry legumes, chocolate, and beverages, such as tea, coffee, or wine. Experimental studies on animals or cultured human cell lines support a role of polyphenols in the prevention of cardiovascular diseases, cancers, neurodegenerative diseases, diabetes, or osteoporosis. However, it is very difficult to predict from these results the effects of polyphenol intake on disease prevention in humans. One of the reasons is that these studies have often been conducted at doses or concentrations far beyond those documented in humans. The few clinical studies on biomarkers of oxidative stress, cardiovascular disease risk factors, and tumor or bone resorption biomarkers have often led to contradictory results. Epidemiological studies have repeatedly shown an inverse association between the risk of myocardial infarction and the consumption of tea and wine or the intake level of some particular flavonoids, but no clear associations have been found between cancer risk and polyphenol consumption. More human studies are needed to provide clear evidence of their health protective effects and to better evaluate the risks possibly resulting from too high a polyphenol consumption.

Dietary polyphenols and the prevention of diseases

Human intervention trials have provided evidence for protective effects of various (poly)phenol-rich foods against chronic disease, including cardiovascular disease, neurodegeneration, and cancer. While there are considerable data suggesting benefits of (poly)phenol intake, conclusions regarding their preventive potential remain unresolved due to several limitations in existing studies. Bioactivity investigations using cell lines have made an extensive use of both (poly)phenolic aglycones and sugar conjugates, these being the typical forms that exist in planta, at concentrations in the low-μM-to-mM range. However, after ingestion, dietary (poly)phenolics appear in the circulatory system not as the parent compounds, but as phase II metabolites, and their presence in plasma after dietary intake rarely exceeds nM concentrations. Substantial quantities of both the parent compounds and their metabolites pass to the colon where they are degraded by the action of the local microbiota, giving rise principally to small phenolic acid and aromatic catabolites that are absorbed into the circulatory system. This comprehensive review describes the different groups of compounds that have been reported to be involved in human nutrition, their fate in the body as they pass through the gastrointestinal tract and are absorbed into the circulatory system, the evidence of their impact on human chronic diseases, and the possible mechanisms of action through which (poly)phenol metabolites and catabolites may exert these protective actions. It is concluded that better performed in vivo intervention and in vitro mechanistic studies are needed to fully understand how these molecules interact with human physiological and pathological processes.

Dietary (Poly)phenolics in Human Health: Structures, Bioavailability, and Evidence of Protective Effects Against Chronic Diseases

Dietary phenolics: chemistry, bioavailability and effects on health.

Health effects of quercetin: from antioxidant to nutraceutical.

Saponins are steroid or triterpenoid glycosides, common in a large number of plants and plant products that are important in human and animal nutrition. Several biological effects have been ascribed to saponins. Extensive research has been carried out into the membrane-permeabilising, immunostimulant, hypocholesterolaemic and anticarcinogenic properties of saponins and they have also been found to significantly affect growth, feed intake and reproduction in animals. These structurally diverse compounds have also been observed to kill protozoans and molluscs, to be antioxidants, to impair the digestion of protein and the uptake of vitamins and minerals in the gut, to cause hypoglycaemia, and to act as antifungal and antiviral agents. These compounds can thus affect animals in a host of different ways both positive and negative.

/pdf/the-biological-action-of-saponins-in-animal-systems-a-review-21yt7p784a.pdf

The biological action of saponins in animal systems: a review

Flavonoids are polyphenolic plant secondary metabolites with antioxidant and other biological activities potentially beneficial to health. Food-borne flavonoids occur mainly as glycosides, some of which can be absorbed in the human small intestine; however, the mechanism of uptake is uncertain. We used isolated preparations of rat small intestine to compare the uptake of the quercetin aglycone with that of some quercetin glucosides commonly found in foods, and investigated interactions between quercetin-3-glucoside and the intestinal hexose transport pathway. The nature of any metabolism of quercetin and its glucosides during small intestinal transport in vitro was determined by HPLC. The presence of quercetin-3-glucoside in the mucosal medium suppressed the uptake of labeled galactose by competitive inhibition and stimulated the efflux of preloaded galactose. Quercetin-3-glucoside and quercetin-4'-glucoside, but not quercetin-3,4'-diglucoside, were transported into everted sacs significantly more quickly than quercetin aglycone. Intact quercetin glucosides were not detected in mucosal tissue or within the serosal compartment, but both free quercetin and its metabolites were present, mainly as quercetin-3-glucuronide and quercetin-7-glucuronide. Evidently, quercetin derived from quercetin-3-glucoside passes across the small intestinal epithelium more rapidly than free quercetin aglycone. Monoglucosides of quercetin interact with the sodium-dependent glucose transporter. During passage across the epithelium, quercetin-3-glucoside is rapidly deglycosylated and then glucuronidated.

/pdf/intestinal-transport-of-quercetin-glycosides-in-rats-30o4k11si8.pdf

Intestinal Transport of Quercetin Glycosides in Rats Involves Both Deglycosylation and Interaction with the Hexose Transport Pathway

The effect of two gel-forming polysaccharide gums, guar gum and Na-carboxymethyl-cellulose (CMC), on glucose transport in vitro was investigated using everted sacs of rat jejunum. The gums were added to the mucosal bathing media to give apparent viscosities in the range of 1-110 Pascal seconds X 10(-3), mPa.s(cP). Serosal glucose transport fell steeply by about 60% as the viscosities of the mucosal media rose to 20mPa.s, and levelled off thereafter. A similar effect was observed in sacs preincubated with guar gum (15 minutes) and exposed to glucose in a subsequent guar-free incubation. Glucose transport with and without the addition of guar gum was found to be sensitive to mucosal stirring, so that, when shaken at 130 oscillations per minute, sacs exposed to guar gum (0.25 %, viscosity c.a. 16 mPa.s (cP) transported glucose at a similar rate to sacs incubated without guar at 80 oscillations per minute. By measuring the time course for the establishment of osmotic induced potentials, it was shown that incubation with guar or CMC led to an increase in the apparent thickness of the unstirred fluid layer overlying the mucosa (guar-free thickness = 317 +/- 15 mu, guar treated thickness = 468 +/- 25 mu). It is suggested that the presence of a polysaccharide gum in the fluid film surrounding the villi increases its viscosity, and thus gives rise to a thickening of the rate-limiting unstirred layer. If such an effect occurs in vivo, this could contribute to the diminished post-prandial glycaemia observed in human subjects fed guar gum.

https://gut.bmj.com/content/gutjnl/22/5/398.full.pdf

Effect of gel-forming gums on the intestinal unstirred layer and sugar transport in vitro.

Polyphenolic compounds are abundant throughout the plant kingdom and are found in a wide variety of human foods. The flavonoids, which are the best defined group of polyphenols in the human diet, themselves comprise a large and complex group, all of which contain a three-ring structure with two aromatic centres and a central oxygenated heterocycle. Recent evidence suggests that significant quantities of quercetin and possibly myricetin and kaempferol are absorbed in the gut. A larger fraction probably remains in the lumen, and thus a substantial proportion of the gastrointestinal mucosa is exposed to biologically significant concentrations of these compounds. A substantial body of experimental work has established that flavonoids can suppress carcinogenesis in animal models and there is considerable interest in the biological effects of these compounds at the cellular level. Flavonoids interact with cellular signal pathways controlling the cell cycle, differentiation and apoptosis. Their potentially antineoplastic effects include antioxidant activity, induction of Phase II enzyme activity, inhibition of protein kinases and interactions with Type II estrogen binding sites. Naturally occurring polyphenolic compounds may play a role in the protective effects of fruits and vegetables against cancers in general, and they appear to have considerable potential for pharmaceutical uses as chemopreventive agents against neoplastic changes in the alimentary tract. Future research should therefore focus on the biological effects of flavonoids in the human body, using biomarkers to define their effects at each stage in the onset of neoplasia.

Polyphenolic compounds: interactions with the gut and implications for human health.

A wide variety of plant-derived compounds, including the polyphenolic flavonoids, is present in the human diet or is consumed for medicinal reasons. Epidemiological and animal studies tend to suggest a protective effect of flavonoids against cardiovascular diseases and some types of cancer. Although flavonoids have been studied for about 50 years, the cellular mechanisms involved in their biological activity are still largely unknown. Antioxidant properties of the flavonoids have been postulated as a mechanism for putative protective effect against cardiovascular disease. Nevertheless, these properties alone are not sufficient to explain the anti-carcinogenic potential of these polyphenols. The mechanisms by which the molecules interact with cells or are absorbed by them are very important for determining the intracellular concentration and distribution of the metabolites to internal organs. With the exception of the cells lining the gastrointestinal tract, all other cells in the body are only exposed to flavonoid metabolites and degradation products. No previous studies have addressed this aspect of cellular exposure, except for some methylated metabolites. Within the last decade, reports on flavonoid activities have been largely associated with enzyme inhibition and anti-proliferative activity. From our recent work on the human colon cancer cell line HT29 and comparison with published studies, structure-function relationships demonstrate that antioxidant, enzyme inhibitor or anti-proliferative activities are dependent on particular structure motifs. The present review also presents a summary of mechanistic data on a few elected compounds.

/pdf/evidence-for-consistent-patterns-between-flavonoid-3gip25199w.pdf

Evidence for consistent patterns between flavonoid structures and cellular activities.

Quinoa (Chenopodium quinoa) is a valuable source of protein in some parts of South America, and it is likely to be exploited further in both developing and industrialised countries. However, quinoa seeds contain significant levels of saponins which are potential antinutrients. In the present study, the effects of processing on the quantity and composition of saponins in quinoa products were determined, and the biological effects of quinoa grain and cereal products containing high or low levels of saponins were investigated both in vitro and in vivo in the rat. Quinoa saponins were shown to be membranolytic against cells of the small intestine and to cause an increase in mucosal permeability in vitro. Unwashed bitter quinoa caused a significant food aversion and poor food conversion efficiency in rats. However, processing quinoa, during the manufacture of an infant cereal, reduced the concentration and membranolytic activity of saponins, and increased the palatability and nutritional quality of the cereal product to a level similar to that of a wheat-based cereal product.

Saponins of quinoa (Chenopodium quinoa): Effects of processing on their abundance in quinoa products and their biological effects on intestinal mucosal tissue

J. M. Gee

Papers

Intestinal Transport of Quercetin Glycosides in Rats Involves Both Deglycosylation and Interaction with the Hexose Transport Pathway

Effect of gel-forming gums on the intestinal unstirred layer and sugar transport in vitro.

Polyphenolic compounds: interactions with the gut and implications for human health.

Evidence for consistent patterns between flavonoid structures and cellular activities.

Saponins of quinoa (Chenopodium quinoa): Effects of processing on their abundance in quinoa products and their biological effects on intestinal mucosal tissue