**4. Green tea and antioxidant**

Green tea is a traditional drink made from the Camellia sinensis tree, which is widely consumed in various countries, especially in Asia. Polyphenols from green tea, especially its active component, namely EGCG (epigallocatechin-3-gallate), have received more attention because they have potential therapeutic agents to prevent neurodegeneration, inflammatory diseases, and cancer [25, 61, 62]. The ability of green tea is mainly due to its antioxidant, free radical scavenger, metal chelation, anticancer, anti-apoptotic, and anti-inflammatory properties [26].

EGCG is roughly composed of four derivatives based on structural variations, including Epicatechin (EC), Epigallocatechin (EGC), Epicatechin gallate (ECG), and epigallocatechin-3-gallate (EGCG). EGCG consists of 10% dry green tea extract and about 50–80% or 200–300 mg of one cup of brewed green tea (**Figure 2**) [26, 63].

The metabolism of green tea polyphenols in the body has been widely studied. It is reported that green tea polyphenols are absorbed, distributed, metabolized, and excreted within 24 hours. In humans, when given 1.2 g of green tea that has been decaffeinated, within 1 hour, it will increase plasma levels by 46−268 ng/ml and excreted in the first 24 hours in the range of 1.6−3.2 mg. Therefore, drinking 6 cups of green tea a day will increase the concentration of green tea polyphenols by 12 times and will be sufficient for antioxidant activity against oxidative damage. These data are then supported by animal studies, where giving green tea 35 mg/kg/day will prevent oxidative damage and memory regression and can delay aging [6, 25, 52, 59, 63].

Free radicals, including ROS and nitrogen species such as NO, superoxide, and hydroxyl free radicals, are naturally produced to support the host defense system against oxidative stress and inflammation stimulated by pathogens and infections. Still, these species have two natural faces, namely, in the event of free radicals that the host produces. Excessive amounts in the body will cause destructive processes that cause DNA, protein, and lipid damage, leading to apoptosis and cell death [65, 66].

*Green Tea with Its Active Compound EGCG for Acute Ischemic Stroke Treatment DOI: http://dx.doi.org/10.5772/intechopen.107068*

#### **Figure 2.**

*The structure of green tea catechins and their four derivatives have antioxidant effects, namely Epicatechin, Epigallocatechin, Epicatechin-3-gallate, and epigallocatechin-3-gallate [26, 64].*

Green tea polyphenol compounds are biological antioxidants that have a radical scavenger effect. Green tea contains two ingredients that have potent antioxidant properties, namely EGCG and ECG. This antioxidant ability is caused by the presence of ortho-trihydroxy groups in the B chain, 4-keto and 5-hydroxyl in the C chain, and galloyl moiety in the A chain. The difference in antioxidant activity in EGCG and ECG is very slight, which is related to each group's hydroxyl group. Therefore, these molecules can generally clean the radical group 1,1-diphenyl-3-picrylhydrazyl, as well as peroxyl radicals, NO, free fatty radicals, singlet oxygen, peroxynitrite, hydroxyl free radicals, and superoxide anions through three mechanisms, namely, by chelating the metal ion into an inactive form, direct interaction between catechin and peroxyl radicals through electron transfer to prevent DNA damage, and prevent free radical deamination by forming semi-quinone stable radicals [36, 61, 67].

EGCG is reported to be more effective as a radical scavenger when compared to vitamin E and vitamin C. When compared between green tea derivatives, EGCG (epigallocatechin-3-gallate) > ECG (Epicatechin gallate) > EGC (Epigallocatechin) > EC (Epicatechin) has a positive effect. Antioxidant, while EGC > EGCG>EC > EGC has a protective effect in vitro. The ability as a scavenger radical is due to the presence of ortho-3′,4′-dihydroxy moiety groups, or ortho-trihydroxy groups and is not based on steric structure. An increase in the number of hydroxyl groups will increase the strength of EGCG as a radical scavenger because of the presence of three hydroxyl groups in the B chain group and also consisting of galloyl moiety with three hydroxyl groups in the C chain [6, 26, 36, 68].

Oral administration of EGCG in vivo research showed a decrease in lipid peroxide levels by increasing levels of enzymatic and non-enzymatic antioxidants. EGCG can also completely reverse the effect of AlCl3 through its superoxide dismutase activity and by increasing glutathione peroxidase, Cyt-C oxidase, and acetylcholine esterase. The study aimed to see the impact of improving EGCG in rats and found

an improvement in the levels of enzymatic and non-enzymatic antioxidants in about 50% of malondialdehyde levels and a 39% decrease in protein carbonyl in both groups of rats. This effect was also obtained by reducing the dose from 100 to 2 mg/KgBW [26].

Consumption of green tea in humans also shows an increase in antioxidant levels in the body. Long-term consumption of green tea as much as 2−3 cups a day is reported to increase antioxidant activity and total polyphenols, accompanied by a decrease in lipid peroxide, glutathione and hydroperoxide levels. This shows that green tea polyphenols such as EGCG can directly or indirectly affect antioxidant levels to reduce oxidative stress [26, 31, 69].

Besides functioning as a radical scavenger, EGCG also has a chelating effect on heavy metals. Two structures give rise to this chelating effect, including ortho-3′,4′ dihydroxy moiety and 4-keto, 3-hydroxyl or 4-keto and 5-hydroxyl moiety groups. This structure serves as a binding point for heavy metal transitions. It neutralizes their activity by converting from the active form to an inactive redox complex and preventing oxidative damage to cells. In vitro studies using astrocyte cultures have demonstrated the ability of many flavonoids to diffuse, which is also supported by in vivo studies. Administration of EGCG orally for 5 to 10 days indicates the presence of these molecules in brain tissue; this shows the ability of EGCG to penetrate the blood– brain barrier [33, 36, 66, 70].
