**7. Green tea**

**6.2. Flavinoid**

10 Current Trends in Atherogenesis

vonoid containing ingredients [32].

yield a variety of biological effects.

function and apoptosis [32,41].

sions occurring in atherosclerosis.

ing activity [27,40].

Flavonoids, many of which are polyphenolic compounds, are believed to be beneficial for the prevention and treatment of atherosclerosis and CVDs mainly by decreasing oxidative stress and increasing vasorelaxation [32,40,41]. More than 8.000 different flavonoids have been described and since they are prerogative of the kingdom of plants, they are part of human diet with a daily total intake amounting to 1 g, which is higher than all other classes of phytochemicals and known dietary anti-oxidants. In fact, the daily intake of vita‐ min C, vitamin E and β-carotene from food is estimated minor of 100 mg. A number of dif‐ ferent factors, such as harvesting, environmental factors and storage, may affect the polyphenol content of plants. Additional variability in flavonoid content could be expected in finished food products because its availability is largely dependent on the cultivar type, geographical origin, agricultural practices, post-harvest handling and processing of the fla‐

Flavonoids are widely distributed in the plant and are categorized as flavonol, flavanol, fla‐ vanone, flavone, anthocyanidin and isoflavone. Quercetin is one of the most widely distrib‐ uted flavonoids, which are abundant in red wine, tea and onions. Quercetin intake is therefore suggested to be beneficial for human health and its anti-oxidant activity should

The major flavanols in the diet are catechins. They are abundant in green tea (about 150mg/ 100ml) and lesser extent in black tea (13.9 mg/100 ml) where parent catechins are oxidized into complex polyphenols during fermentation. Red wine (270 mg/L) and chocolate (black chocolate: 53.5 mg/100 g; milk chocolate: 15.9 mg/100 g) are also sources of catechins [34].

Polyphenols and/or flavonoids exhibit a variety of beneficial biological effects, including an‐ ti-oxidant, anti-hypertensive, anti-viral, anti-inflammatory and anti-tumor activities; more‐ over some flavonoids have also been reported to modulate insulin resistance, endothelial

Many studies have shown that flavonoids demonstrate protective effects against the initia‐ tion and progression of atherosclerosis. The bioactivity of flavonoids and related polyphe‐ nols appears to be mediated through a variety of mechanisms, though particular attention has been focused on their direct and indirect anti-oxidant actions. In particular, it has been shown that the consumption of flavinoids limits the development of atheromatous lesions, inhibiting the oxidation of LDL, which is considered a key mechanism in the endothelial le‐

Mechanisms of anti-oxidant effects include also: suppression of ROS formation either by in‐ hibition of enzymes or chelating trace elements involved in free radical production, scaveng ROS and upregulation or protection of anti-oxidant defences [32]. The phenolic hydroxyl groups of flavonoids, which act as electron donors, are responsible for free radical scaveng‐

Tea, a beverage consumed worldwide, is a source of both pleasure and healthful benefits. Originally recommended in traditional Chinese medicine, green tea (*Camellia sinensis*) has gained considerable attention due to its anti-oxidant, anti-inflammatory, anti-hypertensive, anti-diabetic and anti-mutagenic properties [42].

Green tea constitutes 20%-22% of tea production and is principally consumed in China, Ja‐ pan, Korea and Morocco. Green tea, or non-fermented tea, contains the highest amount of flavonoids, in comparison to its partially fermented (oolong tea) and fermented (black tea) counterparts and, due to its high content of polyphenolic flavonoids, has shown unique car‐ diovascular health benefits. In green tea, catechins comprise 80% to 90% of total flavonoids, with epigallocatechin gallate, being the most abundant catechin (48–55%), followed by epi‐ gallocatechin (9–12%), epicatechin gallate (9–12%) and epicatechin (5–7%) [42]. The catechin content of green tea depends on several factors including how the leaves are processed be‐ fore drying, preparation of the infusion and decaffeination, as well as the form in which it is distributed in the market (instant preparations, iced and ready-to-drink teas have been shown to contain fewer catechins) [43]. When tea leaves are rolled or broken during indus‐ try manufacture, catechins come in contact with polyphenol oxidase, resulting in their oxi‐ dation and the formation of flavanol dimers and polymers known as theaflavins and thearubigins [44].

ability of tea catechins or flavonols. Two studies in humans found that the addition of milk decreased or eliminated increase in plasma anti-oxidant capacity induced by tea consump‐

Atherosclerosis and Current Anti-Oxidant Strategies for Atheroprotection

http://dx.doi.org/10.5772/53035

13

Nevertheless, a diet rich in foods containing anti-oxidant polyphenols, like green tea bever‐ ages, combined with physical activity and a correct diet may offer primary prevention against CVDs. While future clinical trials could further elucidate the cardioprotective bene‐ fits of green tea beverages, on the basis of existing reports, freshly prepared green tea ap‐

Studies of the herbal medicines for the prevention and treatment of atherosclerosis have re‐ ceived much attention in recent years. Single compounds isolated from some herbal materi‐ als have been shown to reduce the production or remove the build up of cholesterol *in vitro* or *in vivo* studies. Glabrol from Glycyrrhiza glabra has been found to be an acyl-coenzyme A: a cholesterol acyltransferase inhibitor that blocks the esterification and intestinal absorp‐ tion of free cholesterol. Curcumin from Curcuma longa inhibited cholesterol accumulation. Puerarin from Pueraria lobata can promote cholesterol excretion into bile by upregulating the rate-limiting enzyme in the synthesis of bile acid from cholesterol. Moreover, these ex‐ tracts have anti-oxidative effects and may reduce the levels of ox-LDL and increased the lev‐

Pomegranate juice consumption slowed atherosclerosis progression through the potent anti-

Pomegranate fruit (*Punica granatum L.*) has been rated to contain the highest anti-oxidant ca‐ pacity in its juice, when compared to other commonly consumed polyphenol rich beverages. The anti-oxidant capacity of pomegranate juice was shown to be three times higher than that of red wine and green tea, based on the evaluation of the free-radical scavenging and iron reducing capacity [30]. It was also shown to have significantly higher levels of anti-oxidants in comparison to commonly consumed fruit juices, such as grape, cranberry, grapefruit or orange juice. The principal anti-oxidant polyphenols in pomegranate juice are ellagitannins and anthocyanins. Ellagitannins account for 92% of the anti-oxidant activity of pomegranate juice and are concentrated in peel, membranes and piths of the fruit. The bioavailability of pomegranate polyphenols is affected by several factors, including: interindividual variabili‐ ty, differential processing of pomegranate juice, as well as the use of analytical techniques

sensitive enough to detect low postprandial concentrations of these metabolites [30].

One pomegranate fruit contains about 40% of an adult's recommended daily requirement of vitamin C and is high in polyphenol compounds. The pomegranate plant contains alkaloids,

pears to be a healthy dietary choice to consider as an atheroprotective strategy.

tion, whereas another found no effect [44].

**8. Herbal**

els of HDL [48].

**9. Pomegranate juice**

oxidant properties of pomegranate polyphenols [35].

Tea leaves destined to become black tea are rolled and allowed to ferment, resulting in rela‐ tively high concentrations of theaflavins and thearubigins and relatively low concentrations of catechins. Consequently, green tea contains relatively high concentrations of catechins and low concentrations of theaflavins and thearubigins. It is important to underline that black tea administration to LDL receptor-deficient mice did not affect aortic fatty streak le‐ sion area, although fatty streak lesion areas in the same animal model supplemented with anti-oxidants, such as vitamin C, vitamin E and β-carotene, were 60% smaller than those of control animals [44,45]. On the other hand, green tea catechins have been shown to inhibit formation of ox-LDL, may decrease linoleic acid and arachidonic acid concentrations [46], elevate serum anti-oxidative activity and prevent or attenuate decreases in anti-oxidant en‐ zyme activities [44]. In addition to having anti-oxidant properties, green tea catechins have also been shown to reduce VSMCs proliferation [42].

In particular, Erba et al. (2005) showed a significant decrease in plasma peroxide levels, DNA oxidative damage and LDL oxidation, as well as a significant increase in total anti-oxi‐ dant activity in the plasma of healthy volunteers who consumed two cups of green tea per day in addition to a balanced and controlled diet demonstrating that green tea may act syn‐ ergistically with a correct diet in affecting the biomarkers of oxidative stress [47]. Much of the evidence supporting anti-oxidant functions of tea polyphenols is derived from assays of their anti-oxidant activity *in vitro*. However, evidence that tea polyphenols are acting direct‐ ly or indirectly as anti-oxidants *in vivo* is more limited [44].

It is very important to underline also that while green tea beverage consumption is con‐ sidered part of a healthy lifestyle, green tea extracts supplements should be used with caution. Very high doses of green tea extracts (6 g–240 g) have been associated with hepa‐ totoxicity in patients who used them for a duration of 5 to 120 days, changing in blood bi‐ ochemical parameters included an elevation of serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin and albumin levels. Al‐ though, it was observed a reversal of symptoms when subjects stopped taking the green tea supplement [42].

In addition, in a number of countries, tea is commonly consumed with milk. Interactions be‐ tween tea polyphenols and proteins found in milk have been found to diminish total antioxidant capacity *in vitro*, but it is presently unclear whether consuming tea with milk substantially alters the biological activities of tea flavonoids *in vivo*. The addition of milk to tea did not significantly alter areas under the curve for plasma catechins or flavonols in hu‐ man volunteers, suggesting that adding milk to tea does not substantially affect the bioavail‐ ability of tea catechins or flavonols. Two studies in humans found that the addition of milk decreased or eliminated increase in plasma anti-oxidant capacity induced by tea consump‐ tion, whereas another found no effect [44].

Nevertheless, a diet rich in foods containing anti-oxidant polyphenols, like green tea bever‐ ages, combined with physical activity and a correct diet may offer primary prevention against CVDs. While future clinical trials could further elucidate the cardioprotective bene‐ fits of green tea beverages, on the basis of existing reports, freshly prepared green tea ap‐ pears to be a healthy dietary choice to consider as an atheroprotective strategy.
