**3. Green tea and its clinical values**

#### **3.1 Properties of green tea**

Tea (*Camellia sinensis*) is an aromatic beverage prepared from boiling or simmering of cured leaves. Apart from water, tea is one of the most popular consumed beverages worldwide, with a consumption of 120mL/day/capita (Graham, 1992). Of the different varieties of tea, the most commonly found on the market are white, green, oolong and black tea. And over the last few decades, green tea has been subjected to many scientific and medical studies on its potential health beneficial effects (Table 3).

Anti-aging Anti-bacterial Anti-inflammatory Anti-angiogenic Anti-cancer Lowering blood fat Prevent tooth decay and clear bad breath Enhanced skin whitening

Table 3. Benefits of green tea

Green Tea for Endometriosis 287

functions as a major antioxidant in human LDL (Zhu *et al.*, 1999). Similarly, EGCG and EGC show potent inhibitory effects on LDL oxidation *in vitro*, with EC and ECG being even more effective on protective activity on the depletion of α-tocopherol in LDL. And a clinical study claimed the consumption of 300 mg of green tea polyphenol extract twice daily for 1week

Proliferation and migration of endothelial cells are major events in the angiogenic process for the formation of endometriosis. Matrix metalloproteinase-2 is expressed abundantly in lesions and has been suggested to play a key role in the degradation of the basement membrane, thereby promoting migration of endothelial cells (Zempo *et al.*, 1994). Green tea polyphenols can significantly reduced endothelial cells proliferation in a dose-dependent manner and caused the accumulation of cells in the G1 phase without affecting cell viability (Kojima-Yuasa *et al.*, 2003). In addition, EGCG suppressed endothelial cells proliferation and migration by inducing apoptosis through mitochondrial depolarization, activation of caspase-3 and reduction of binding of VEGF to its receptors in human ECs (Kondo *et al.*,

Cytokines are a group of multifunctional proteins that mediate the regulation of inflammatory responses. These cytokines are expressed in a number of tissues, including macrophages, vascular endothelial cells, adipose tissue and neurons. In general, the role of cytokines can be further classified depending on the way they influence inflammation, such as pro- or anti-inflammatory (Kundu *et al.*, 2008). Factors such as tumor necrosis factor-α, IL-6, IL-1, GM-CSF, interferon-c, and IL-12 played a major role on the induction of the

EGCG has been shown to possess anti-inflammatory properties *in vivo* and *in vitro* (Hamer *et al.*, 2007). The potent effects of tea polyphenols toward inflammation have also been known to cancer prevention (Beltz *et al.*, 2006). Tea polyphenols appear to modulate at different targets the anti-inflammatory activities related to arachidonic acid-dependent pathways, such as cyclooxygenase (COX) inhibition. Within the arachidonic acid-independent pathways, nitric-oxide synthase (NOS) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) are targets of polyphenols (Miles *et al.*, 2005). The released phytochemicals inhibit cyclooxygenase-2 (COX-2) and inducible nitric-oxide synthase (iNOS) expression by blocking NF-κB activation. Particularly EGCG suppresses activation of NF-κB by repression of degradation of inhibitory unit, IκBκ, which hampers subsequent

nuclear translocation of the functionally active subunit of NF-κB (Kundu *et al.*, 2008).

It has been widely shown that green tea have the ability to inhibit angiogenesis in *in vitro* proliferation studies (Laschke *et al.*, 2008; Park *et al.*, 2006; Slivova *et al.*, 2005) and in *in vivo* angiogenesis assays (Laschke *et al.*, 2008; Xu *et al.*, 2009). Anti-angiogenesis plays a crucial role accounting to the cancer-preventive effect made by green tea. As angiogenesis is a complex multi-step process that includes the proliferation, migration and differentiation of endothelial cells into tube-like structures. The initiation of each step involves multiple

can delayed the oxidation of human LDL *ex vivo* (Miura *et al.*, 2000).

**3.2.2 Anti-mitotic** 

2002; Yoo *et al.*, 2002).

**3.2.3 Anti-inflammatory** 

inflammatory response.

**3.2.4 Anti-angiogenic** 

Green tea contains polyphenols, particularly catechins, accounting for 30-40% of the dry weight (Balentine *et al.*, 1997; Graham, 1992). The main components of green tea consist of catechins, minor flavanols and polymeric flavonoids (de Mejia *et al.*, 2009). It contains more catechin concentrations than black tea or oolong tea, due to the minimal oxidation during processing. The compositions of green tea catechins are mainly comprised of (-)-epicathecin (EC), (-)-epigallocatechin (EGC), (-)-epigallocatechin gallate (EGCG), (-)-epicathecin gallatis (ECG), (-)-gallocatechin gallate (GCG), (-)-catechin gallate (CG) and (+)-cathecin (CT) (Miura *et al.*, 1994) (Fig. 2). Among the components of green tea, (-)-epigallocatechin gallate (EGCG) is the most abundant and the most extensively studied catechin, accounting to 50-80% of the total catechins in green tea (Yang *et al.*, 2002).

Fig. 2. The main catechins components found in green tea

#### **3.2 Biological activities**

#### **3.2.1 Anti-oxidant activity**

Free-radical damage has been postulated to contribute to the etiology of aging, and many chronic health problems such as cardiovascular, inflammatory diseases, and cancer (Rice-Evans *et al.*, 1993; Spiteller, 2001). The productions of free radicals, including reactive oxygen species (ROS), are capable of chemically altering many natural bio-molecules in our body, resulting in changes in their structure and function, leading to aging and the development of chronic diseases (McCall *et al.*, 1999).

Like most polyphenols, catechins and procyandins have an anti-oxidant activity. In a study conducted by Guo *et al*, ECG and EGCG displayed better antioxidant activity than EC and EGC on lipid peroxidation (Guo *et al.*, 1996). Also, green tea catechins have been shown to protect or regenerate α-tocopherol in human low-density lipo-protein (LDL), which

Green tea contains polyphenols, particularly catechins, accounting for 30-40% of the dry weight (Balentine *et al.*, 1997; Graham, 1992). The main components of green tea consist of catechins, minor flavanols and polymeric flavonoids (de Mejia *et al.*, 2009). It contains more catechin concentrations than black tea or oolong tea, due to the minimal oxidation during processing. The compositions of green tea catechins are mainly comprised of (-)-epicathecin (EC), (-)-epigallocatechin (EGC), (-)-epigallocatechin gallate (EGCG), (-)-epicathecin gallatis (ECG), (-)-gallocatechin gallate (GCG), (-)-catechin gallate (CG) and (+)-cathecin (CT) (Miura *et al.*, 1994) (Fig. 2). Among the components of green tea, (-)-epigallocatechin gallate (EGCG) is the most abundant and the most extensively studied catechin, accounting to 50-80% of the

total catechins in green tea (Yang *et al.*, 2002).

Fig. 2. The main catechins components found in green tea

Free-radical damage has been postulated to contribute to the etiology of aging, and many chronic health problems such as cardiovascular, inflammatory diseases, and cancer (Rice-Evans *et al.*, 1993; Spiteller, 2001). The productions of free radicals, including reactive oxygen species (ROS), are capable of chemically altering many natural bio-molecules in our body, resulting in changes in their structure and function, leading to aging and the development of

Like most polyphenols, catechins and procyandins have an anti-oxidant activity. In a study conducted by Guo *et al*, ECG and EGCG displayed better antioxidant activity than EC and EGC on lipid peroxidation (Guo *et al.*, 1996). Also, green tea catechins have been shown to protect or regenerate α-tocopherol in human low-density lipo-protein (LDL), which

**3.2 Biological activities 3.2.1 Anti-oxidant activity** 

chronic diseases (McCall *et al.*, 1999).

functions as a major antioxidant in human LDL (Zhu *et al.*, 1999). Similarly, EGCG and EGC show potent inhibitory effects on LDL oxidation *in vitro*, with EC and ECG being even more effective on protective activity on the depletion of α-tocopherol in LDL. And a clinical study claimed the consumption of 300 mg of green tea polyphenol extract twice daily for 1week can delayed the oxidation of human LDL *ex vivo* (Miura *et al.*, 2000).

#### **3.2.2 Anti-mitotic**

Proliferation and migration of endothelial cells are major events in the angiogenic process for the formation of endometriosis. Matrix metalloproteinase-2 is expressed abundantly in lesions and has been suggested to play a key role in the degradation of the basement membrane, thereby promoting migration of endothelial cells (Zempo *et al.*, 1994). Green tea polyphenols can significantly reduced endothelial cells proliferation in a dose-dependent manner and caused the accumulation of cells in the G1 phase without affecting cell viability (Kojima-Yuasa *et al.*, 2003). In addition, EGCG suppressed endothelial cells proliferation and migration by inducing apoptosis through mitochondrial depolarization, activation of caspase-3 and reduction of binding of VEGF to its receptors in human ECs (Kondo *et al.*, 2002; Yoo *et al.*, 2002).
