HPLC analysis of catechin compositions in six green tea extract solutions (2 g%,
Brewed tea has been the most widely consumed beverage throughout history. Attractively, this is attributed to its present taste, aromatic odor and healthful effects to the human body. Tea (
2. Sources and compositions of green tea
Tea has traditionally been cultivated across four continents in the manufacturing of a refreshing drink. The tea products that are available are directly related to the process used at the origin, and can be classified as black tea, green tea, yellow tea, red tea, green pressed tea, as well as instant tea and tea dyes . Green tea is manufactured by using conventional and modified methods. One of these methods involves a 2-3-day process of to drying fresh tea leaves and then rolling the dry leaves with a commercial machine. Alternatively, another method involves the very rapid process of baking the tea leaves in a house-hold microwave oven (800 watt, 3 minutes) at a working temperature of 115 ºC. This process will shock the persisting PPO enzyme and result in higher catechins content . A typical green tea beverage is normally prepared at a proportion of 1 g dry weight of tea leaves in 100 ml of hot water in a 3-minute brew (an approximate temperature of 80 ºC). This brew usually contains 250 – 350 mg tea solids, 30 – 42% catechins (74 mg) and 3–6% caffeine . HPLC analysis shows the green tea extract (GTE) is comprised of at least six major catechins, including (-)-epicatechin (EC), (-)-epicatechin 3-gallate (ECG), (-)-epigallocatechin (EGC), (-)-epigallocatechin 3-gallate (EGCG), (+)-catechin (C) and (-)-gallocatechin (GC), of which EGCG is the major isomer followed by ECG, EGC and EC (Figure 1) . Gallic acid (GA) is derivatized to one of the hydroxyl groups of the catechins, which has been directly attributed to the biological activities of the catechin species.
Moreover, tea products have different amounts and compositions of catechins, which is possibly due to biodiversity, different processing methods, different planting areas and different varieties of tea strains. For instance, Khokhar and colleagues reported that 1 g dry weight of tea product contained 48.4 mg total catechins (9.1 mg EGC, 7.9 mg EC, 22.9 mg EGCG, and 8.5 mg ECG) for Ceylon (NL) black tea; 5.6 mg total catechins (<0.5 mg EGC, 3.1 mg EC, 1.8 mg EGCG, and 0.8 mg ECG) for Yule (India) black tea; 7.5 mg total catechins (<0.5 mg EGC, 4.0 mg EC, 2.6 mg EGCG, and 1.0 mg ECG) for PG tips (UK) black tea;5.15 mg total catechins (16.3 mg EGC, 4.7 mg EC, 26.3 mg EGCG, and 4.4 mg ECG) for Chinese green tea; 84.9 mg total catechins (28.7 mg EGC, 9.4 mg EC, 40.8 mg EGCG, and 5.9 mg ECG) for Japanese green tea; and 21.1 mg total catechins (7.7 mg EGC, 1.7 mg EC, 11.5 mg EGCG, and 0.5 mg ECG) for Chinese oolong tea . EGCG has so far received the most attention because it represents approximately 59% catechin content, EGC at approximately 19%, ECG at approximately 13.6%, and EC at approximately 6.4% of the total catechin content . Green tea also contains other phenolic acids, such as chlorogenic acid and caffeic acid, as well as other flavonols, such as kaempferol, myricetin and quercetin .
Green tea catechins have proven to be quite stable in water that is room temperature; however, they can be destroyed at a rate of 20% under brewing at 98 ºC for 7 hours and epimerized to other derivatives (e.g. EGCG → GCG) under autoclaving at 120 ºC for 20 minutes . Fresh tea leaves are unusually rich in polyphenolic catechins that may constitute up to 30% of the dry leaf weight . As a result of the immediate inactivation of PPO enzyme, the compositions of catechins in green tea are very similar to those of the fresh tea leaves. Various quinines, which are subsequently produced by the enzymatic oxidations, undergo condensation reactions to produce
In our Thai green tea, EGCG was found to be the most abundant catechin (at about 60% of the total catechin content), followed by EGG, ECG, and EC, respectively and the assay yield of the total green tea catechin content was found to be 26-29 g/100 g dry tea leaves (Table 1) . In comparison, Taiwan green tea (1 g dry weight) contained 93.3 mg total catechin content, followed by 43.2 mg EGCG, 33.6 mg ECG, 0.7 mg C, 3.3 mg EC and 2.7 mg ECG .
|mg/g dry weight||169.4±7.2||60.1±6.2||19.3±2.6||16.3±5.6||279.8±15.2|
3. Nutritional value of green tea
In general, an antioxidant refers to any substance capable of preventing the oxidation catalyzed by reactive oxygen species (ROS)/reactive nitrogen species (RNS). Thus, an antioxidant that protects against iron toxicity is a substance that can: i) chelate iron and prevent the reaction with oxygen or peroxides; ii) chelate iron and maintain it in a redox state that makes iron unable to reduce molecular oxygen; iii) trap already formed radicals, which is a putative action of any substance that can scavenge free radicals in biological systems, regardless of whether they have originated from iron-dependent reactions or not. Not only can natural products chelate iron, but also synthetic compounds are capable of chelating iron
The potential of green tea to prevent or ameliorate chronic diseases is currently the subject of considerable scientific investigations. Although a number of mechanisms have been proposed for their beneficial effects, the radical scavenging and antioxidant properties of green tea catechins are frequently cited as important contributors. Emerging evidence has also shown that catechins and their metabolites possessmany additional mechanisms of action  by affecting numerous sites, potentiating endogenous antioxidants and eliciting dual actions during oxidative stress. Much of the evidence supporting an antioxidant function for green tea catechins is derived from assays of their antioxidant activity
4. Anti-oxidative and iron-chelating properties
Green tea catechins stoichiometrically bind ferric ion to form a redox-inactive iron-phenolic complex [15, 16] and potentially protect vital biomolecules from oxidative damage. Incredibly, the catechins could be capable of chelating excessive redox iron in iron overloaded diseases, such as thalassemia, and play important preventive or/and protective roles in this unpleasant condition [2, 17-19]. The phytochemical compounds therefore play a double role in reducing the rate of oxidation because they can participate in: i) iron chelation , and ii) trapping radicals [2, 20]. Catechins can protect culture cells from iron-mediated damage [21, 22], ameliorate iron accumulation  and inhibit hepatic iron-induced lipid oxidation , and also play a dual effect in decreasing labile plasma iron (LPI) in iron-loaded rats . Animal studies offer a unique opportunity to assess the contribution of green tea administration to the physiological effects on different models of oxidative-related diseases. In a combination of free-radical scavenging activity with iron-chelating properties, green tea may have a capacity of chelating excess iron in iron-overloaded conditions and play important preventive and/or protective roles in this unpleasant condition.
Like the deferiprone (DFP) treatment, oral administrations of GTE and EGCG significantly lowered levels of plasma non-transferrin bound iron (NTBI) and LPI in wild-type (WT), heterozygous β-globin gene knockout (BKO) thalassemic and double heterozygous β-globin gene knockout carrying human βE gene (DH) mice (strain C57BL/6J) with iron overload, when compared to the DW group (Table 2) (Sakaewan Ounjaijean and Somdet Srichairatanakool, unpublished data). Elimination of these two toxic irons by green tea extract and EGCG fraction would relieve redox iron-induced oxidative stress and tissue damage in the body. GTE treatment efficiently depleted plasma malondialdehyde (MDA) concentrations in the iron-loaded mice (approximately 50% in WT, 30% in BKO and 40% in DH mice), whereas EGCG treatment caused significantly lower plasma MDA levels (approximately 30% in all the mice), suggesting that GTE and EGCG are strong antioxidants and exert potent anti-plasma lipid peroxidation. Consistently, the GTE and EGCG increased levels of reduced glutathione (GSH) in the plasma of all the mice despite under iron overload. Thus, it can be said that green tea catechins, particularly EGCG, chelate the redox irons and consequently inhibit the iron-catalyzed lipid peroxidation reactions in plasma lipids, as well as membrane phospholipids, resulting in an improvement of a powerful antioxidants as reduced glutathione is reduced in the plasma compartment.
|WT (n = 24)||-0.27±0.23||11.17±0.26*||6.83±1.49†||6.80±1.75†||6.81±2.23†|
|BKO (n = 16)||0.34±0.26||19.78±1.36*||10.20±1.92†||10.66±1.60†||11.75±1.21†|
|DH (n = 10)||-0.07±0.11||13.41±1.84*||7.74±1.38†||7.81±0.71†||7.83±1.41†|
|WT (n = 24)||-2.49±1.00||1.19±0.42*||-2.26±1.98†||-2.47±1.25†||-2.01±2.76†|
|BKO (n = 16)||0.87±0.22||2.30±1.08*||0.30±2.57†||-0.21±1.37†||0.35±1.05†|
|DH (n = 10)||-0.15±0.52||0.81±0.26*||0.26±0.61†||0.47±0.63||0.34±0.70|
|WT (n = 24)||13.39±5.10||39.97±8.67*||23.26±8.30†||28.39±6.66†||32.58±8.73†|
|BKO (n = 16)||26.80±3.59||54.34±9.88*||37.62±9.23†||41.85±11.8†||52.29±7.51†|
|DH (n = 10)||18.79±2.31||46.89±4.56*||26.62±5.14†||32.72±2.46†||38.13±5.09†|
|WT (n = 24)||11.53±2.50||7.73±4.70*||15.15±7.72†||16.04±6.61†||15.89±8.43†|
|BKO (n = 16)||7.73±4.25||6.24±3.89||15.12±9.76*,†||15.63±7.74*,†||16.50±8.75*,†|
|DH (n = 10)||10.97±5.00||5.81±1.44*||14.78±5.16†||17.03±7.27†||14.19±4.89†|
5. Fate of green tea catechins in the body
5.1. Gastrointestinal absorption
Among these polyphenolic compounds, the hierarchy of antioxidant activity is ECG > EGCG > EGC > GA > EC ≈ C . With the chelating activity of such prooxidant metals as iron (Fe2+), green tea is able to reduce dietary nonheme iron absorption . The ratio of EGC, EGCG, ECG or EC to the iron was 3:2, 2:1, 2:1 and 3:1, respectively . Unlike most flavonoids, tea catechins existing as aglycone are found in the blood following oral ingestion and subsequently metabolized in the liver by methylation, sulfation and glucoronidation reactions . Structure-activity studies have shown that the presence of the galloyl ring in the 3-position and trihydroxyphenyl B ring are of significant importance in terms of the antioxidant properties of the catechins .
After green tea (25 mg/kg) and pure EGCG fractions (10 mg/kg) were intravenously administered into rats, a study of the pharmacokinetic (concentration-time curves) properties of the catechins in the plasma was conducted. Beta-elimination half-lives (T1/2β) were found to be 212, 45, and 41 minutes; clearances were 2.0, 7.0, and 13.9 ml•minute/kg; and apparent distribution volumes (Vd) were 1.5, 2.1, and 3.6 dl/kg for EGCG, EGC, and EC, respectively. In comparison, EGCG had a shorter T1/2β (135 minute), a larger clearance (72.5 ml•minute/kg), and a larger volume (Vd) (22.5 dl/kg) than the other two. When the green tea was intragastrically given (200 mg/kg), around 0.1, 13.7 and 31.2% of EGCG, EGC and EC were detected in the plasma compartment. The EGCG level was found to be the highest in the intestine samples and declined with a T1/2 of 173 minute. EGC and EC levels were found to be the highest in the kidneys and declined rapidly with T1/2 of 29 and 28 minute, respectively. EGCG, EGC, and EC levels in the liver and lungs were lower than those recorded in the intestine and the kidney . This implies that EGCG is mainly excreted through bile, while EGC and EC are excreted through urine and bile. Inter-individual variations in the bioavailability of green tea catechins can be substantial and may be due, in part, to differences in colonic microflora and genetic polymorphisms among the enzymes involved in polyphenol metabolism . The effect of green tea drinking may also differ by genotype .
Following oral administration of green tea catechin solutions (0.6%,
5.2. Organ metabolism
EC was not glucuronidated by uridine diphosphate-glucuronosyltransferases (UGT) and sulfotransferases (SULT) in human liver and small intestinal microsomes. However, the compound was efficiently glucuronidated in rat liver microsomes with the formation of two different glucuronides, and was also sulfated in human liver cytosol, mainly through the SULT1A1 isoform, as well as in the intestine through the SULT1A1 and SULT1A3 isoforms. In comparison, the EC was much less sulfated in the rat liver than in the human liver . EGCG and ECG constituents in green tea drinks (10%,
Most polyphenolic catechins in green tea may not be absorbed in the small intestine. The nonabsorbed catechins will be converted by large bow bacterial flora into simpler phenolic compounds, such as hippuric acid, then absorbed into the blood and excreted in the urine (4.22±0.28 mmol/24 hours), when compared to non-consumption (1.89+0.28 mmol/24 hours) .
6. Health benefits
6.1. Health promotion
The potential health effects of green tea catechins depend not only on the amount consumed, but also on their bioavailability, which appears to be substantially varied. Following the oral administration of tea catechins to rats  and mice , the four principal catechins have been identified in the portal vein, indicating that tea catechins are absorbed intestinally. There appear to be species-related differences in the bioavailability of EGCG compared to other tea catechins . The epicatechin isomers purified from green tea were effective agents in protecting human low-density lipoproteins (LDL) and red blood cell (RBC) membranes from oxidative modification . These effects are partly due to their free-radical scavenging abilities  and their iron-chelating properties, which are capable of binding any available iron, thus greatly reducing their bioavailability. They also have many pharmacological properties, including anti-hypertensive , anti-atheroslcerotic , anti-carcinogenic [43-45] and hypocholesterolemic effects [46, 47]. Health benefits of green tea consumption were achieved in the rodents within relatively short periods: three weeks , four weeks [49, 50], five weeks [51, 52] and eight weeks [53, 54].
Surprisingly, catechins inhibited xanthine oxidase (XO) activity
6.2. Hematologic disorders
In consideration of the evidence for its iron chelating properties, strong antioxidant capacity, low toxicity, and orally available administration, green tea has potential to be used as a pharmacological agent in the management of diseasesrelated to iron overload. Hypothetically, the removal of iron could reduce oxidative damage to the cellular biomolecules, including lipids, proteins, carbohydrates and nucleic acids, and this can consequently prevent, as well as improve the vital organ dysfunctions. DFP, known to readily permeate and mobilize nonheme iron from β-thalassemic patient erythrocytes, serves as a benchmark against which orally effective agents; catechins in GTE and purified EGCG products have been compared. Our studies have paid particular attention to the efficacy of GTE and EGCG in terms of the aspects of anti-oxidation and the potential for iron chelation in order to alleviate oxidative stress and iron overload in β-thalassemic mice in the past experiments, and in Thai β-thalassemia patients with regard to the near future.
Though the pathological role of redox iron in the hemosiderosis (such as hereditary hemochromatosis and thalassemia) is well characterized, excessive accumulation of the iron can result in significant organ dysfunction and abnormality. Recognition of the role of iron in conditions beyond transfusion-dependent iron overload may bring significant implications for the management of metabolic, infectious, and degenerative diseases. New findings obtained during the past years, especially in terms of the discovery of mutations in the genes associated with brain iron metabolism, have provided key insights into the mechanisms of brain iron homeostasis and the pathological mechanisms responsible for neurodegenerative diseases. Increased iron in the brain, which is rich in oxygen and fatty acids, provides an ideal environment for oxidative stress and possible irreparable tissue damage. Oxidative stress, resulting from increased brain iron levels, and possibly also from defects in antioxidant defense mechanisms, is widely believed to be associated with neuronal death in brain disorders.
The interaction between iron overload and dietary antioxidants has been well characterized; especially, with respect to vitamins E and C. Vitamin E has been extensively studied with respect to its capacity to protect molecules from the
The interaction of another dietary antioxidant, vitamin C (ascorbic acid) and iron is less clear. Ascorbic acid can reduce ‘free iron’ (ferric) to a ferrous form, promoting the initiation and propagation of free radical reactions [66, 67]. In people under a risk of iron overload, in which the elevated levels of iron could lead to higher ‘free iron’ concentrations, an excess of vitamin C could have deleterious effects. Plant flavonoids (including rutin and curcumin) are another group of antioxidants, which may have therapeutic potential in thalassemia. However, despite their apparent salutary effects on erythrocytes, antioxidants have not yet been shown to ameliorate the anemia of the patients . Antioxidants may be more effective if used in combination with an iron chelator. This approach, if successful, could be particularly useful in countries with limited financial resources.
The potential of green tea to prevent or ameliorate chronic disease is currently the subject of considerable scientific investigation. Although a number of mechanisms have been proposed as being responsible for green tea’s beneficial effects, the radical scavenging and antioxidant properties of green tea catechins are frequently cited as important contributors. Emerging evidence has shown that catechins and their metabolites have many additional mechanisms of action  by affecting numerous sites, potentiating endogenous antioxidants and eliciting dual actions during oxidative stress. Much of the evidence supporting the antioxidant function for green tea catechins has been derived from assays of their antioxidant activity
|Month 0||Month 1||Month 2||Month 0||Month 1||Month 2||Month 0||Month 1||Month 2|
(n = 24)
(n = 16)
(n = 10)
(n = 10)
(n = 10)
(n = 10)
(n = 8)
(n = 8)
(n = 8)
(n = 8)
(n = 8)
(n = 8)
The inhibition of the growth of blast cells from patients with acute myelocytic leukemic (AML) by EGCG affected hematopoietic growth factors (HGF), granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF) or interleukin-3 (IL-3), was useful in terms of the stimulation of leukemic cell proliferation. EGCG dosage and time dependently reduced the survival of NSF60 leukemic cell lines [69, 70]. These factors can lead to an induction of cell apoptosis, including endonuclease activation, p53 induction, caspase 3 protease activation
Surprisingly, EGCG diminished the phosphorylation of vascular endothelial growth factor (VEGF) receptors, potent angiogenic cytokines that are essential for the survival of tumor cells in the autocrine pathway, in chronic lymphocytic leukemia B cells that have been isolated from leukemic patients, leading to cell apoptosis . EGCG decreased human telomerase reverse transcriptase (hTERT) promoter methylation and histone H3 Lys9 acetylation, but increased hTERT repressor E2F-1 binding at the promoter of MCF-7 breast cancers and HL60 promyelocytic leukemia cell cultures . EGCG treatment induced death-associated protein kinase 2 (DAPK2) in multiple myeloma cells and dose dependently increased levels of the DAPK2 in HL60 and NB4 AML cells, while a combined treatment of EGCG (0 – 40 μM) with all-
The results of the phase 2 clinical study demonstrated that patients with early stage CLL consumed GTE (Polyphenon E preparation, dose of 2000 mg/day, twice daily) for 6 months showed decreases in the absolute lymphocyte counts and lymphadenopathy .
6.3. Cardiovascular diseases
Epigenetics, hypercholesterolemia, diabetes, hypertension, heavy smoking, physical inactivity, stress and obesity are all risk factors for atherosclerosis and cardiovascular diseases (CVD). Green tea catechins have been reported to exert anti-obesity effects, including a reduction of adipocyte differentiation and proliferation; decreases in lipogenesis, fat mass, body weight, fat absorption, plasma levels of triglycerides, free fatty acids, cholesterol, glucose, insulin and leptin; and increases in β-oxidation and thermogenesis.
Yang and Koo reported that the ECG and EGCG that are present in Chinese green tea reduced lipid deposition-caused weight, as well as the cholesterol content of the liver, importantly lowered levels of serum cholesterol levels and the atherogenic index in the rats fed with a cholesterol-enriched diet . Rats fed with the green tea powder (20 g/kg)-enriched diet showed a significant increase in the lag-phase oxidation of plasma with very low density in lipoproteins (VLDL) and LDL by 33% when compared to the control diet . EGCG was proposed to be a competitive inhibitor of β-ketoacyl reductase of the FAS enzyme complex in the liver . EGCG and ECG lowered FAS and malate enzymes in rat liver cytosol, resulting in a significant decrease in visceral fat deposition and hepatic triglyceride content . Nonetheless, experiments showed that GTE lowered serum cholesterol and triglyceride concentrations in the hamsters fed with high fat diet (200 g lard and 1 g cholesterol/kg) in a concentration-dependent manner, for which the mechanism was most likely due to its influence on the absorption of dietary fat and cholesterol, but not on the inhibition of the synthesis of cholesterol or fatty acid . Another study supports the evidence that Chinese green tea lowered plasma cholesterol levels by increasing fecal bile acids and cholesterol excretion, but not by inhibiting activities of three major lipid metabolizing enzymes, including 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-Co A) reductase, cholesterol 7α-hydroxylase and FAS . More importantly, high plasma cholesterol levels, fatty liver, renal dysfunctions and severe atherosclerotic aorta were observed in the LDL knockout mice fed with a normal diet, but not in those fed with a 4% green tea catechins-enriched diet for 35 weeks .
GTE, which had greater effects than oolong tea and black tea, decreased high serum triglyceride (195 vs. 119 mg/dl) and cholesterol (104 vs. 73 mg/dl) levels to normal levels, and also decreased hepatic triglyceride content in sucrose-induced hyperlipidemic rats (8.4±1.5 vs. 27.7±7.9 mg/g wet weight (
Green tea catechins functioned against membrane phospholipid peroxidation , showed a strong synergistic anti-oxidative activity with α-tocopherol in micelles ,as well as in human LDL levels , and had a protective effect of high-density lipoprotein (HDL) on endothelial cell-dependent vasodilatation . They have many pharmacological activities, including anti-hypertensive  and anti-atherosclerotic [86, 87] effects. Clearly, green tea catechins; especially EGCG, has a potential hypolipidemic effect, possibly by interfering with the emulsification, digestion, and micellar solubilization of lipids in the critical steps of intestinal absorption of dietary lipids . Bursill and coworkers found that GTE (2% catechins,
6.4. Neurological diseases
The errors in brain iron metabolism found in neurological disorders are found to be multifactorial, however treatment conditions seem to be particularly important. Epilepsy, an oxidative related disorder of the brain, has served as a model for the investigation in the role of iron, especially NTBI in neurological disorders. The effect of antiepileptic drug treatment on changes of iron status and oxidative stress parameters were determined . Recent genetic and biochemical manipulations of iron overload have placed iron at the centre of research into neurodegenerative diseases. This is supported by the discovery of genetic and non-genetic misregulations of the iron metabolism in these disorders. In many neurodegenerative disorders, abnormally high levels of iron in specific regions of the brain have been reported . Evidence for iron contribution to diseases by augmentation of oxidative stress have led to an examination of the contribution of iron to other diseases, in which oxidative stress may be involved, including epilepsy . It has not been possible to determine whether the accumulated iron is in the labile iron pool (LIP), which can participate in the Fenton reaction to generate the reactive hydroxyl radical. The reduction in GSH during disease progression and in response to neurotoxins, together with increased iron accumulation and ROS generation, might be taken as evidence for the presence of free iron .
Oxidative stress, resulting from increased brain iron levels, and possibly also from defects in antioxidant defensive mechanisms, is widely believed to be associated with neuronal death in these disorders [96, 97], along with a reduced availability of GSH and other antioxidant substances in the brain. Changes in the integrity of the blood brain barrier (BBB) due to altered vascularization of the tissue or inflammatory events could be another initial cause. However, neuronal death by any initial cause could lead to large amounts of iron release and increased ROS formation . Therefore, iron and iron-induced oxidative stress could possibly be a common mechanism involved in the development of neurodegeneration  (Figure 3). Available data strongly support this hypothesis [100, 101]
Based on this hypothesis, therefore, therapeutic efforts should be devoted to reducing brain iron levels and inhibiting the generation of ROS. A few recent studies have shown that the iron chelator, deferrioxamine, may be a significant factor in an effective therapy for the prevention and treatment of brain disorders . One possible non-toxic approach with natural metal chelators could make use of green tea catechins, especially EGCG. This compound comprising antioxidant, iron chelating and anti-inflammatory activities; has been shown to be neuroprotective in animal models of Parkinson’s disease (PD) and Alzheimer’s disease (AD), and also regulates the processing of amyloid precursor protein (APP) through a non-amyloidogenic pathway [103, 104]. Understanding the timing of iron mismanagement in relation to the progression of neuronal losses would provide important information on pathogenesis, and would raise the possibility of monitoring iron changes as a marker of disease progression, and perhaps even in a pre-clinical diagnosis in conditions where iron misregulation is an early event.
6.5. Mutagenicity and cancinogenesis
Topical applications of green tea polyphenol fractions (such as EGCG, EGC and ECG) inhibitedbenz[a]-pyrene (BP)-and 7,12-dimethylbenz[a]-anthracene (DMBA)-initiated and 12-
Green tea has long been considered a refreshing beverage that is prepared from tea (
AML=acute myelocytic leukemia
APP=amyloid precursor protein
BBB=blood brain barrier
BKO=β-globin gene knockout
CLL=chronic lymphocytic leukemia
DAPK2=death-associated protein kinase 2
DH=double heterozygous β-globin gene knockout carrying human βE gene
DMT1=divalent metal ion transporter-1
FAS=fatty acid synthase
G-CSF=granulocyte colony stimulating factor
GM-CSF=granulocyte macrophage colony stimulating factor
GTE=green tea extract
HGF=hematopoietic growth factors
HMG-Co A=3-hydroxy-3-methylglutaryl-coenzyme A
hTERT=human telomerase reverse transcriptase
HTLV-I=human T-cell lymphotropic virus type I
IDL=intermediate density lipoprotein
IRPs=iron regulatory proteins
LD50=lethal dose at 50%
LIP=labile iron pool
LPI=labile plasma iron
MAPK=mitogen-activated protein kinase
NAD(P)+=nicotinamide adenine dinucleotide phosphate
NAD(P)H=reduced nicotinamide adenine dinucleotide phosphate
NTBI=non-transferrin bound iron
RBC=red blood cell
RNS=reactive nitrogen species
ROS=reactive oxygen species
TEAC=trolox-equivalent antioxidant capacity
Treg=regulatory T cells
VEGF=vascular endothelial growth factor
This work was partially supported by the Office of Higher Education Commission and Mahidol University under the National Research University Initiative, Thailand Research Fund through Professor Suthat Fucharoen, MD. and by a Research Chair Grant from the National Science and Technology Development Agency (NSTDA) and Mahidol University through Professor Suthat Fucharoen, MD.
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