Tea polyphenols: preventive effects and mechanism of actions

The leaves of the tea plant, Camellia sinensis, are rich in compounds with many biological activities, ranging from preventing the development of chronic diseases to reducing the glycemic index of starchy foods.
More than 4000 different molecules have been found in the beverage, of which about one third of these are polyphenols, the most important phytochemicals in determining the nutritional values and health benefits of the tea.
Tea polyphenols are mostly flavonoids. Examples are catechins in green tea, among which epigallocatechin-3-gallate or EGCG is the most important and abundant, and thearubigins and theaflavins in black tea. Their galloyl groups at positions 3 and/or 3′ appear to be particularly important for their effects.

Skeletal formula of epigallocatechin gallate, a catechin, and one of the tea polyphenols
Epigallocatechin Gallate

Other bioactive compounds present in tea leaves are:

  • alkaloids, such as caffeine, theophylline and theobromine;
  • amino acids, and among them, theanine or R-glutamylethylamide, that is also a brain neurotransmitter and one of the most important amino acids in green tea;
  • proteins;
  • carbohydrates;
  • chlorophyll;
  • volatile organic molecules, that contribute to the aroma of the beverage;
  • fluoride, aluminum and trace elements.

CONTENTS

Biological activities of polyphenols

Polyphenols, both in vivo and in vitro, have a broad spectrum of biological activities, such as:

  • antioxidant and prooxidant properties;
  • a protective role against the development of diabetes, hyperlipidemia, and various types of tumors;
  • inhibition of inflammation;
  • antiviral activities;
  • anticariogenic activity.

Hence, there has been a growing interest in recent years toward the possible preventive effects of tea against many diseases, particularly cardiovascular disease, for example in the development and progression of atherosclerosis.

Mechanisms of action of tea polyphenols

Currently, knowledge is accumulating on the effects of tea polyphenols at cellular and molecular level.
It seems, at least in vitro, that catechins, and theaflavins and thearubigins are the compounds responsible for the physiological effects and health benefits of green tea and black tea, respectively.
Among the molecular mechanisms by which tea polyphenols seem to exert their effects, it has been observed, after binding to specific cell membrane receptors, a change in the activity of various protein kinases that then phosphorylate target proteins, such as transcription factors, that, in turn, translocate into the nucleus and modify the gene expression. This appears to be the mechanism of action of EGCG, and the mechanism proposed for thearubigins, polymeric polyphenols that, due to their large dimensions, may not be able to cross the plasma membrane.
In addition, some polyphenols could be able to cross the plasma membrane, then binding to specific cytoplasmic, mitochondrial or nuclear targets.
And, depending on the cell type and their amount, tea polyphenols can activate or inhibit certain cellular processes.

Tea polyphenols and starch digestion

Tea polyphenols exert an inhibitory effect on starch digestion.
In vitro studies have shown that green tea extracts, which contain monomeric polyphenols, have an equal inhibitory effect on starch digestibility of wheat bread and gluten-free bread, whereas black tea extracts, rich in tannins, namely, polymeric polyphenols, are less effective against wheat bread. Therefore, it seems that the inhibitory effect of tannins is negatively influenced by gluten, whereas gluten has a lower inhibitory effect on monomeric polyphenols.
The inhibitory effect of these phytochemicals has been attributed to various molecular mechanisms briefly described below.

  • A competitive inhibition on pancreatic alpha-amylase. The galloyl groups are thought  to be important for this effect.
  • The inhibition of other digestive enzymes present in the gastrointestinal tract.
  • The direct interaction with starch. Tea polyphenols can interact with starch granules through hydrogen bonds and hydrophobic forces, thus reducing the available surface to react with digestive enzymes.
  • Conversely, gluten could reduce the amount of polyphenols able to interact with starch and therefore able to inhibit its digestion.

Tea polyphenols could represent a means for controlling the glycemic index of starchy foods. However, it should be emphasized that, for example in the case of bread, to achieve an inhibitory effect, 100 g of bread must be co-digested with 2.5 cups of green tea or 2 cups of black tea.

References

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Dwyer J.T. and Peterson J. Tea and flavonoids: where we are, where to go next. Am J Clin Nutr 2013;98:1611S-1618S. doi:10.3945/ajcn.113.059584

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Isoflavones: chemical structure, foods and health effects

Isoflavones are colorless polyphenols belonging to the flavonoid family.
Unlike the majority of the other flavonoids, they have a restricted taxonomic distribution, being present almost exclusively in the Leguminosae or Fabaceae plant family, mainly in soy.
Since legumes, soy in primis, are a major part of the diet in many cultures, these flavonoids may have a great impact on human health.
They are also present in beans and broad beans, but in much lower concentrations than those found in soy and soy products.
Also red clover or meadow clover (Trifolium pratense), another member of Leguminosae family, is a good source.
Currently, they are not found in fruits and vegetables.

Together with phenolic acids, such as caffeic acid and gallic acid, and quercetin glycosides, they are the most well-absorbed polyphenols, followed by flavanones and catechins (but not gallocatechins).

In plants, some isoflavones have antimicrobial activity and are synthesized in response to attacks by bacteria or fungi; thus they act as phytoalexins.

CONTENTS

Chemical structure of isoflavones

While most flavonoids have B ring attached to position 2 of C ring, isoflavones have B ring attached to position 3 of C ring.

Basic skeleton structure of isoflavones, polyphenols belonging to the flavonoid family
Basic Skeleton of Isoflavones

Even if they are not steroids, they have structural similarities to estrogens, particularly estradiol. This confers them pseudohormonal properties, such as the ability to bind estrogen receptors; therefore, they are classified as phytoestrogens or plant estrogens. The benefits often ascribed to soy and soy products (e.g. tofu) are believed to result from the ability of isoflavones to act as estrogen mimics .
It should be underlined that the binding to estrogen receptors seems to lose strength with time, therefore their potential efficacy should not be overestimated.
In foods, they are present in four forms:

  • aglycone;
  • 7-O-glucoside;
  • 6′-O-acetyl-7-O-glucoside;
  • 6′-O-malonyl-7-O-glucoside.

Soy isoflavones: genistein, daidzein and glycitein

Soy and soy products, such as soy milk, tofu, tempeh and miso, are the main source of isoflavones in the human diet.
The isoflavone content of soy and soy products varies greatly as a function of growing conditions, geographic zone, and processing; for example, in soy it ranges between 580 and 3800mg/kg fresh weight, while in soy milk it range between 30 and 175 mg/L. The most abundant isoflavones in soy and soy products are genistein, daidzein and glycitein, generally present in a concentration ratio of 1:1:0,2.; biochanin A and formononetin are other isoflavones present in less concentrations.

Basic skeleton structure of isoflavones genistein, daidzein, glycitein, biochanin A, formononetin
Isoflavones

The 6′-O-malonyl derivatives have a bitter, unpleasant, and astringent taste; therefore they give a bad flavor to the food in which they are contained. However, being sensitive to temperature, they are often hydrolyzed to glycosides during processing, such as the production of soy milk.
The fermentation processes needed for the preparation of certain foods, such as tempeh and miso, determines in turn the hydrolysis of glycosides to aglycones, i.e. the sugar-free molecule.
Isoflavone glycosides present in soy and soy products can also be deglycosylated by β-glucosidases in the small intestine.
The aglycones are very resistant to heat.
Although many compounds present in the diet are converted by intestinal bacteria to less active molecules, other compounds are converted to molecules with increased biological activity. This is the case of isoflavones, but also of prenylflavonoids from hops (Humulus lupulus), and lignans, that are other phytoestrogens.

Phytoestrogens and menopause

Vasomotor symptoms, such as night sweats and hot flashes, and bone loss are very common in perimenopause, also called menopausal transition, and menopause. Hormone replacement therapy (HRT) has proved to be a highly effective treatment for the prevention of menopausal bone loss and vasomotor symptoms.
The use of alternative therapies based on phytoestrogens is increased as a result of the publication of the “Women’s Health Initiative” study, that suggests that hormone replacement therapy could lead to more risks than benefits, in particular an increased risk of developing some chronic diseases.
Soy isoflavones are among the most used phytoestrogens by menopausal women, often taken in the form of isoflavone fortified foods or isoflavone supplements.
However, many studies have highlighted the lack of efficacy of soy isoflavones, and red clover isoflavones, even in large doses, in the prevention of vasomotor symptoms (hot flushes and night sweats) and bone loss during menopause.

References

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