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I. Green Tea
C. By Foods to prevent and treat diseases
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world. Some researchers suggested that the catechin polyphenols constituents of green tea, which were for long time regarded merely as dietary antioxidants, have caught our and other scientist's attention because of their diverse pharmacological activities, which have been allied to a possible beneficial action on brain health. This review will elaborate on the impact of nutritional supplementation on brain function in general, and provide a compilation of the most updated literature on epidemiology, clinical and animal studies with green tea polyphenols in ageassociated cognitive decline and in fighting neurodegenerative diseases(1).
In the study of to examine the acute effects of L-theanine in comparison with a standard benzodiazepine anxiolytic, alprazolam and placebo on behavioural measures of anxiety in healthy human subjects using the model of anticipatoryanxiety (AA), indicated that some evidence for relaxing effects of L-theanine during the baseline condition on the tranquil-troubled subscale of the VAMS. Alprazolam did not exert any anxiolytic effects in comparison with the placebo on any of the measures during the relaxed state. Neither L-theanine nor alprazalam had any significant anxiolytic effects during the experimentally induced anxiety state(1). Others study suggested that L-theanine does not produce anxiolysis by modulation of the GABAA receptor; however, in combination with midazolam, a synergistic or additive effect was demonstrated by decreased anxiety and both fine and basic motor movements. These data may provide direction for further studies examining L-theanine and its effects on anxiety and motor activity(2).
In the study to investigate the role of green tea extract in reversing cardinal behavioral changes and aberrations in oxidative stress induced by valproate exposure. Young mice of both genders received a single dose of valproate (400mg/kg subcutaneously) on postnatal day 14 followed by a daily dose of greentea extract (75 and 300mg/kg) orally up to postnatal day 40, showed that a significant improvement in behavioral assessments particularly with 300mg/kg ofgreen tea extract. Formation of markers of oxidative stress was reduced at both dose levels. Histological findings confirm the neuroprotective effect of green tea at a dose of 300mg/kg. In conclusion it can be stated that green tea exerts neuronal cytoprotective action possibly due to anti-oxidant action and could be efficacious in the management of autism(3).
4. Alzheimer's disease
Epigallocatechin, including catechins, is a phytochemical of Flavan-3-ols, in the group of Flavonoids (polyphenols), found abundantly in green tea, St John wort, black Tea, carob flour, Fuji apples, etc.
In the investgation of the green tea compound epigallocatechin-3-gallate (EGCG) in inhibition of Alzheimer's disease β-amyloid peptide (Aβ) neurotoxicity, showed that EGCG interferes with the aromatic hydrophobic core of Aβ. The C-terminal part of the Aβ peptide (residues 22-39) adopts a β-sheet conformation, whereas the N-terminus (residues 1-20) is unstructured. The characteristic salt bridge involving residues D23 and K28 is present in the structure of these oligomeric Aβ aggregates as well. The structural analysis of small-molecule-induced amyloid aggregates will open new perspectives for Alzheimer's disease drug developmen(4).
In the review of Green tea's active ingredient, epigallocatechin 3-gallate (EGCG), dr. Ahmed S. at the College of Pharmacy summarized that the limitations of the dose, pharmacokinetics, and bioavailability of EGCG in experimental animals and findings related to the EGCG-drug interaction. Although these findings provide scientific evidence of the anti-rheumatic activity of EGCG, further preclinical studies are warranted before phase clinical trials could be initiated with confidence for patients with joint diseases(5).
6. Rheumatoid Arthritis (RA)
EGCG in experimental animals and findings related to the EGCG-drug interaction. Although these findings provide scientific evidence of the anti-rheumatic activity of EGCG, further preclinical studies are warranted before phase clinical trials could be initiated with confidence for patients with joint diseases(6).
7. Coronary heart disease and diabetes
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
In the investigation of theaflavin-enriched green tea extract in association with cholesterol levels of the study of "Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial" by Maron DJ, Lu GP, Cai NS, Wu ZG, Li YH, Chen H, Zhu JQ, Jin XJ, Wouters BC, Zhao J.(5), researchers found that The theaflavin-enriched green tea extract is an effective adjunct to a low-saturated-fat diet to reduce LDL-C in hypercholesterolemic adults and is well tolerated.
b. Immune system
In the investigation of the immunomodulatory effects of decaffeinated green teaextract in rain bow of the study of "Immunomodulatory effects of decaffeinatedgreen tea (Camellia sinensis) on the immune system of rainbow trout (Oncorhynchus mykiss)" by Sheikhzadeh N, Nofouzi K, Delazar A, Oushani AK.(6), researchers found that showed that decaffeinated green tea in lower doses of administration could be optimum to enhance the immunity of rainbow trout.
c. Antioxidant Activity
In the investigation of l-Theanine is a unique amino acid in green tea effects on ethanol-induced liver injury of the study of "l-Theanine prevents alcoholic liver injury through enhancing the antioxidant capability of hepatocytes" by Li G, Ye Y, Kang J, Yao X, Zhang Y, Jiang W, Gao M, Dai Y, Xin Y, Wang Q, Yin Z, Luo L(7), researchers found that l-theanine significantly inhibited ethanol-induced reduction of mouse antioxidant capability which included the activities of SOD, CAT and GR, and level of GSH. These results indicated that l-theanine prevented ethanol-induced liver injury through enhancing hepatocyte antioxidant abilities.
In the evaluation of Abstract Tea (Camellia sinensis) effects in type II diabetes management of the study of "Anti-Hyperglycemia Properties of Tea (Camellia sinensis) Bioactives Using In Vitro Assay Models and Influence of Extraction Time" by.Ankolekar C, Terry T, Johnson K, Johnson D, Barbosa AC, Shetty K(8), researchers wrote that tea offers an attractive potential strategy to regulate postprandial hyperglycemia toward an overall dietary support for type 2diabetes management.
In the study to evaluate the effect of green tea extract (-)-Epigallocatechin-3-gallate (EGCG) in cultured rabbit lens epithelial cells in order to pave a new way to postcapsular opacity (PCO) prevention, found that Green Tea Constituent(-)-Epigallocatechin-3-gallate could inhibit cultured rabbit lens epithelial cells proliferation by inducing their apoptosis in the concentration used by us, which indicates that it is possible to prevent PCO by using herb extract(7).
Biosynthesized tea polyphenols showed antichlamydial activity against Chlamydiatrachomatis D/UW-3/Cx and L2/434/Bu using cell culture. The most active compounds were (-)-epigallocatechin gallate and (-)-epicatechin gallate, followed by (-)-epicatechin (EC). (+)-Epicatechin and (-)-epigallocatechin were intermediate(4). other researchers found In vitro inhibitory effects of tea polyphenols on the proliferation of Chlamydia trachomatis and Chlamydiapneumoniae(8).
10. Chronic fatigue syndrome (CFS)
In the study to investigate chronic fatigue produced in mice by subjecting them to forced swim inside a rectangular jar of specific dimensions for 6 min. daily for 15 days. Epigallocatechin gallate (EGCG; 25, 50 and 100 mg/kg, p.o., showed that behavioural and biochemical alterations were restored after chronic treatment with EGCG. The present study points out that EGCG could be of therapeutic potential in the treatment of chronic fatigue(9).
11. Autoimmune diseases
In the review of supplemented by hitherto unpublished data of the authors and their coworkers, shows that the intake of polyphenols contained in natural sources, such as hydroxytyrosol, tyrosol, oleuropein (olives), naringin and hesperidin (Citrus fruits), resveratrol, procyanidins or oligomeric procyanidin (grapes or grape seed extracts), (-)-epigallocatechin gallate (green tea) and quercetin (grapes, green tea) etc., are able to modulate chronic inflammatorydiseases, such as type 2 diabetes, rheumatoid arthritis, inflammatory boweldisease, etc(10).
In the study of the effects of 4 different concentrations of catechins and theaflavins were evaluated on 5 isolates each of 5 Candida species employing an agar diffusion growth inhibition assay, showed that both polyphenols showed anti-Candida activity against all tested Candida species and demonstrated a MIC of 6.25 mg/ml for C. albicans. C. glabrata was found to be the most sensitive species followed by C. parapsilosis, C. albicans, C. krusei and C. tropicalis (p < 0.05 for all). Significant intraspecies variations in sensitivity were noted among C. parapsilosis and C. tropicalis (p < 0.001) for both polyphenols. Theaflavins displayed standard PAFE while catechins showed a paradoxical PAFE with all isolates of C. albicans. SEM revealed considerable cell wall damage of C. albicans cells exposed to thepolyphenols(11).
In the review of the emerging evidence for green tea in stroke prevention, showed that green tea is a safe and cheap beverage. Its consumption should be encouraged because it could potentially serve as a practical method for strokeprevention(4). Other suggested that Potential mechanisms by which tea and coffee phytochemicals can exert effects for CVD protection include the regulation of vascular tone through effects on endothelial function, improved glucose metabolism, increased reverse cholesterol transport and inhibition of foam cell formation, inhibition of oxidative stress, immunomodulation and effects on platelet function (adhesion and activation, aggregation and clotting). The phytochemical compounds in tea and coffee and their metabolites are suggested to influence protective endogenous pathways by modulation of gene-expression. It is not known exactly which compounds are responsible for the suggestive protective effects oftea and coffee. Although many biologically active compounds have been identified with known biological effects, tea and coffee contain many unidentified compounds with potential bioactivity(12).
In the study to investigate the antidepressant-like effects and the possible mechanism of action of green tea in widely used mouse models of depression, found that GTP has antidepressant-like effects, and this action did not induce nonspecific motor changes in mice. Green tea polyphenols also reduced serum corticosterone and ACTH levels in mice exposed to the FST. The present study demonstrated that GTP exerts antidepressant-like effects in a mouse behavioral models of depression, and the mechanism may involve inhibition of the hypothalamic-pituitary-adrenal axis(13).
15. Crohn's disease
The bioactive compound epigallocatechin-3-gallate (EGCG), a major component ofgreen tea, has been shown to target histamine-producing cells producing great alterations in their behavior, with relevant effects on their proliferative potential, as well as their adhesion, migration, and invasion potentials. EGCG has been shown to have potent anti-inflammatory, anti-tumoral, and anti-angiogenic effects and to be a potent inhibitor of the histamine-producing enzyme, histidine decarboxylase. Herein, we review the many specific effects of EGCG on concrete molecular targets of histamine-producing cells and discuss the relevance of these data to support the potential therapeutic interest of this compound to treat inflammation-dependent diseases(14).
In the study to evaluate the antiangiogenesis mechanism of epigallocatechin-3-gallate (EGCG) in an endometriosis model in vivo. Dr. Xu H, and the research team atThe Chinese University of Hong Kong, showed that GCG, but not vitamin E, inhibited microvessels in endometriotic implants. EGCG selectively suppressed vascular endothelial growth factor C (VEGFC) and tyrosine kinase receptor VEGF receptor 2 (VEGFR2) expression. EGCG down-regulated VEGFC/VEGFR2 signaling through c-JUN, interferon-γ, matrix metalloproteinase 9, and chemokine (C-X-C motif) ligand 3 pathways for endothelial proliferation, inflammatory response, and mobility. EGCG also suppressed VEGFC expression and reduced VEGFR2 and ERK activation in endothelial cells. VEGFC supplementation attenuated the inhibitory effects by EGCG(15).
In the study to investigate the effect of epigallocatechin gallate (EGCG) on ratleiomyoma (ELT3) cells in vitro and in a nude mice model, found that Inhibitory effect of EGCG (200 micromol/L) on ELT3 cells was observed after 24 hours of treatment (P < .05). At > or = 50 micromol/L, EGCG significantly decreased PCNA and Cdk4 protein levels (P < .05). In vivo, EGCG treatment dramatically reduced the volume and weight of tumors at 4 and 8 weeks after the treatment (P < .05). The PCNA and Cdk4 protein levels were significantly reduced in the EGCG-treated group (P < .05)(1). Others suggested that the tumors in the EGCG fed birds were smaller than those found in the control birds (P = .001). Serum and liver malondialdehyde and TNF-alpha concentrations decreased (P = .001) with EGCG supplementation. The results indicate that dietary supplementation with EGCG reduces the incidence and size of spontaneously occurring leiomyoma of the oviduct in Japanese quail. Clinical trials should be conducted to investigate the efficacy of EGCG supplementation in the prevention and treatment of uterineleiomyoma in humans(16).
18. Flu (influenza)
In an observational study to determine the association between green teaconsumption and the incidence of influenza infection among schoolchildren, showed that the adjusted OR associated with the consumption of green tea for ≥6 d/wk compared with <3 d/wk was 0.60 [(95% CI = 0.39-0.92); P = 0.02] in cases ofinfluenza confirmed by the antigen test. Meanwhile, the adjusted OR inversely associated with the consumption of 1 cup/d to <3 cups/d (1 cup = 200 mL) and 3-5 cups/d compared with <1 cup/d were 0.62 [(95% CI = 0.41-0.95); P = 0.03] and 0.54 [(95% CI = 0.30-0.94); P = 0.03], respectively. However, there was no significant association with the consumption of >5 cups/d. Our findings thus suggest that the consumption of 1-5 cups/d of green tea may prevent influenza infection in children(17).
Quercetin, a ubiquitous plant flavonoid, has been identified to inhibit NS3 activity in a specific dose-dependent manner in an in vitro catalysis assay, showed thatquercetin has a direct inhibitory effect on the HCV NS3 protease. These results point to the potential of quercetin as a natural nontoxic anti-HCV agent reducing viral production by inhibiting both NS3 and heat shock proteins essential for HCV replication(18).
Researchers at the Institute for Basic Research in Developmental Disabilities, in the study of
Digallate dimers of (-)-epigallocatechin gallate inactivate herpes simplex virus, found that all EGCG dimers inactivated enveloped viruses with class I, class II, and class III (HSV-1, HSV-2) fusion proteins more effectively than did monomeric EGCG. EGCG had no activity against the nonenveloped viruses tested, but TF-3 reduced the titer of 4 of 5 nonenveloped viruses by ≅2 to 3.5 log(10). Results also showed that HSV-1 glycoprotein B (gB) was aggregated more rapidly by theasinensin A than EGCG, which, when taken together with the nonenvelopedvirus data, suggests that dimers may inhibit the function of viral proteins required for infectivity. Digallate dimers of EGCG appear to have excellent potential as microbicidal agents against HSV at acidic and neutral pHs(19).
20. Human immunodeficiency virus (HIV)
In thye study to investigate the effects of EGCG on Tat-induced HIV-1 transactivation and potential mechanisms by which EGCG inhibited activation of NF-κB pathway, found that EGCG supplementation significantly improved the changes associated with Tat-induced oxidative stress by increasing nuclear levels of Nrf2, decreasing levels of NF-κB and ROS production. EGCG reversed Tat-mediated AKT activation and AMPK inhibition in MAGI cells. EGCG inhibited Tat-induced LTR transactivation in a dose-dependent manner and Nrf2 signaling pathway may be the primary target for prevention of Tat-induced HIV-1 transactivation by EGCG, and EGCG also reduce NF-κB activation by inhibiting AKT signaling pathway and activating AMPK signaling pathway(20).
Drinking multiple cups of tea per day is associated with lowering low-density lipoprotein cholesterol (LDL-C). In the study of the impact of a theaflavin-enrichedgreen tea extract on the lipids and lipoproteins of subjects with mild to moderate hypercholesterolemia, indicated that theaflavin-enriched green tea extract is an effective adjunct to a low-saturated-fat diet to reduce LDL-C in hypercholesterolemic adults and is well tolerated(21).
22. HPV (human papilloma virus)
In the study of the inhibitory effects on a variety of enzymatic and metabolic pathways involved in cancer development, showed that Sinecatechins demonstrated growth inhibitory potential in all four human papillomavirus-infected tumor cell lines, which may be attributed to the induction of apoptosis, mediated by cell cycle deregulation. In addition, this antiproliferative effect may contribute to the overall cancer-preventative function and possible direct antiviral activity of sinecatechins that may contribute to external genital and perianal warts clearance(22).
In the study to to examine the hypothesis that supplementation with GT alters insulin resistance and associated cardiovascular risk factors in obese, hypertensive patients, showed that supplementation also contributed to significant (P < .05) decreases in the total and low-density lipoprotein cholesterol and triglycerides, but an increase in high-density lipoprotein cholesterol. In conclusion, daily supplementation with 379 mg of GTE favorably influences blood pressure, insulin resistance, inflammation and oxidative stress, and lipid profile in patients with obesity-related hypertension(23).
24. Genital herpes
EGCG has greater anti-HSV activity than other green tea catechins and inactivates multiple clinical isolates of HSV type 1 (HSV-1) and HSV-2. EGCG reduced HSV-2 titers by >or=1,000-fold in 10 to 20 min and reduced HSV-1 titers by the same amount in 30 to 40 min(24).
In the study to evaluate the effects of tea consumption on the risk of biliary tract cancers and biliary stones. The study included 627 incident cases with biliary tract cancer, 1,037 cases with biliary stones and 959 randomly selected controls with Forty-one percent of the controls were ever tea drinkers, defined as those who consumed at least 1 cup of tea per day for at least 6 months, showed that . After adjustment for age, education and body mass index, among women, ever teadrinkers had significantly reduced risks of biliary stones (OR = 0.73, 95% CI = 0.54-0.98) and gallbladder cancer (OR = 0.56, 95% CI = 0.38-0.83). The inverse relationship between tea consumption and gallbladder cancer risk was independent of gallstone disease(25).
26. Liver disease
In the study to evaluate the association between consumption of green tea and various serum markers in a Japanese population, with special reference to preventive effects of green tea against cardiovascular disease and disorders of theliver, found that Increased consumption of green tea was associated with decreased serum concentrations of total cholesterol (P for trend < 0.001) and triglyceride (P for trend = 0.02) and an increased proportion of high density lipoprotein cholesterol together with a decreased proportion of low and very low lipoprotein cholesterols (P for trend = 0.02), which resulted in a decreased atherogenic index (P for trend = 0.02). Moreover, increased consumption of greentea, especially more than 10 cups a day, was related to decreased concentrations of hepatological markers in serum, aspartate aminotransferase (P for trend = 0.06), alanine transferase (P for trend = 0.07), and ferritin (P for trend = 0.02)(1). Other researchers suggested (-)-epigallocatechin-3-gallate (EGCG) as a new inhibitor of hepatitis C virus (HCV) entry. EGCG is a flavonoid present in green tea extract belonging to the subclass of catechins(26).
a. Antimicrobial activities
In the investigation of Antimicrobial activities of green of the study of "Antimicrobial activities of tea catechins and theaflavins and tea extracts against Bacillus cereus" by Friedman M, Henika PR, Levin CE, Mandrell RE, Kozukue N., researchers found that flavonoids in green tea has exerted its ability in protective effects against Bacillus cereus.(27)
b. Immune system
a. In the investigation of the immunomodulatory effects of decaffeinated green teaextract in rain bow of the study of "Immunomodulatory effects of decaffeinatedgreen tea (Camellia sinensis) on the immune system of rainbow trout (Oncorhynchus mykiss)" by Sheikhzadeh N, Nofouzi K, Delazar A, Oushani AK., researchers found that showed that decaffeinated green tea in lower doses of administration could be optimum to enhance the immunity of rainbow trout(27a)
28. Multiple sclerosis
TNFalpha, an imflammatory cytokine has been associated with MS is inhibited by antioxidants of green tea, according to the artcle of Alternative Therapies for Multiple Sclerosis by David Steenblock, M.S., D.O(1). Others sugested that the combination therapy of Glatiramer acetate (GA), an immunomodulatory MS therapeutic, and the neuroprotectant epigallocatechin-3-gallate (EGCG), the main phenol in green tea, have synergistic protective effects in vitro and in the EAE model(28).
In the study to to investigate the antiobesity effect of (-)-epigallocatechin-3-gallate (EGCG) in diet-induced obese mice, showed that green tea EGCG effectively reduces adipose tissue mass and ameliorates plasma lipid profiles in high-fat diet-induced obese mice. These effects might be at least partially mediated via regulation of the expression of multiple genes involved in adipogenesis, lipolysis, beta-oxidation and thermogenesis in white adipose tissue(29).
n the study to investigate whether black tea polyphenol, theaflavin-3,3'-digallate (TFDG) and green tea, epigallocatechin-3-gallate (EGCG)affect MMP activity and osteoclast formation and differentiation in vitro, showed that TFDG and EGCG inhibited the formation and differentiation of osteoclasts via inhibition of MMPs. TFDG may suppress actin ring formation more effectively than EGCG. Thus, TFDG and EGCG may be suitable agents or lead compounds for the treatment of bone resorption diseases(30).
31. Parkinson's disease
In the study of Differential effects of black versus green tea on risk of Parkinson's disease in the Singapore Chinese Health Study, found that total caffeine intake was inversely related to Parkinson's disease risk (p for trend = 0.002); the relative risk for the highest versus lowest quartile was 0.55 (95% confidence interval: 0.35, 0.88). Black tea, a caffeine-containing beverage, showed an inverse association with Parkinson's disease risk that was not confounded by total caffeine intake or tobacco smoking (p for trend = 0.0006; adjusted relative risk for the highest vs. lowest tertile of intake = 0.29, 95% confidence interval: 0.13, 0.67). Green teadrinking was unrelated to Parkinson's disease risk. Diet had no strong influence on risk. Ingredients of black tea other than caffeine appear to be responsible for the beverage's inverse association with Parkinson's disease(31).
In the study to evaluate the efficacy of anti bactericidal activity of tea and catechins against Bordetella pertussis, indicated that pu-erh tea killed the bacteria in a moderate way. (-) Epigallocatechin gallate (EGCg) and theaflavin digallate (TF3) showed also marked bactericidal activity. Green tea and black tea also effectively blocked the adhesion of B. pertussis to HeLa and CHO cells, whereas ECGg and TF3 could not. EGCg and TF3 markedly inactivated leuco-lymphocytosis promoting activity of pertussis toxin. Black tea showed slight but significant inactivation of the activity, whereas green tea showed no inactivation(32).
33. Thyroid disorders
In the comparison of the efficacy of polyphenolic flavonoids found in black and green tea in thyroid function, showed that green tea extract at 2.5 g% and 5.0 g% doses and black tea extract only at 5.0 g% dose have the potential to alter thethyroid gland physiology and architecture, that is, enlargement of thyroid gland as well as hypertrophy and/or hyperplasia of the thyroid follicles and inhibition of the activity of thyroid peroxidase and 5(')-deiodinase I with elevated thyroidal Na+, K+-ATPase activity along with significant decrease in serum T3 and T4, and a parallel increase in serum thyroid stimulating hormone (TSH)(33).
D. Quoted From Foods to prevent and treat cancers
1. Bladder cancer
The ingredient of (--)-Epigallocatechin-3-gallate (EGCG) in green tea have exerted the protective effect to cause bladder cancer cell death. "EGCGs that were physically attached onto the surface of nanogold particles (pNG) was confirmed by scanning electron microscopy. The anticancer activity of the EGCG-adsorbed pNG was investigated in C3H/HeN mice subcutaneously implanted with MBT-2 murinebladder tumor cells. EGCG-pNG was confirmed to inhibit tumor cell growing by means of cell apoptosis" said Dr.Hsieh DS and the research team team at National Taiwan Ocean University(1).
2. Bone cancer (Osteosarcoma(35%))
Dr. Hönicke AS and the research team at University Medicine Greifswald, in the study of The link between cancer and inflammation, found that IL-1Ra and EGCG downregulated IL-1-induced IL-6 and IL-8 release from U-2 OS cells by 65-85%. IL-1Ra and EGCG also reduced secretion of invasiveness-promoting MMP-2 and pro-angiogenic VEGF to 62-75% without affecting the metabolic response and caspase-3 activity. In conclusion, downregulation of IL-1-induced tumorigenic factors (IL-6, IL-8, VEGF, MMP-2) in U-2 OS by IL-1Ra and EGCG may positively affect tumor-associated inflammation and, as a consequence, lead to reduction in angiogenesis and invasiveness. This renders a combined administration of EGCG and IL-1Ra a promising approach as an adjuvant therapy in patients withosteosarcoma(2).
3. Bone cancer (Chondrosarcoma(25%) )
Chondrosarcoma is a malignant primary bone tumor that responds poorly to both chemotherapy and radiation therapy. (-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been shown to inhibit tumorigenesis and cancercell growth in animal models. In the study conducted by National Chung Hsing University, Dr. Yang WH and research team indicated that EGCG induced cell apoptosis in human chondrosarcoma cell lines but not primary chondrocytes. EGCG induced upregulation of Bax and Bak, downregulation of Bcl-2 and Bcl-XL, and dysfunction of mitochondria in chondrosarcoma and EGCG triggered ROS and activated the ASK1-p38/JNK pathway, resulting chondrosarcoma cell death. Importantly, animal studies revealed a dramatic reduction in tumor volume after 24 days of treatment(3)
4. Bone cancer (Ewing's sarcoma(16%))
The insulin-like growth factor I receptor (IGFIR) is constitutively activated in Ewingfamily tumors (EFT) and that the major catechin derivative found in green tea, (-)-epigallocatechin gallate (EGCG), can inhibit cell proliferation and survival of EFT cells through the inhibition of IGFIR activity, as treatment of EFT cell lines with EGCG blocked the autophosphorylation of IGFIR tyrosine residues and inhibited its downstream pathways including phosphoinositide 3-kinase-Akt, Ras-Erk, and Jak-Stat cascades. EGCG treatment was associated with dose- and time-dependent inhibition of cellular proliferation, viability, and anchorage-independent growth, as well as with the induction of cell cycle arrest and apoptosis. Apoptosis in EFT cells by EGCG correlated with altered expression of Bcl-2 family proteins, including increased expression of proapoptotic Bax and decreased expression of prosurvival Bcl2, Bcl-XL, and Mcl-1 proteins. Dr. Kang HG and the research team at Children's Hospital Los Angeles suggested(4)
5. Brain and Spinal Cord Cancer
Epigallocatechin-gallate (EGCG), a main ingredients in green tea has shown protective effect against brain cancer. In the study to investigate the effect of epigallocatechin-gallate (EGCG), the main constituent of green tea polyphenols, on human glioblastoma cell lines U-373 MG and U-87 MG, rat glioma cell line C6, and rat nonfunctioning pituitary adenoma cell line MtT/E, showed that EGCG inhibited viability of MtT/E cells only at a concentration of 100 microg/ml. Quantitative study by flow cytometry demonstrated that lower doses of EGCG (12.5, 25, 50 microg/ml) induced apoptosis in U-373 MG, U-87 MG, and C6 cells; however, only the highest dose (100 microg/ml) induced apoptosis in MtT/E cells. Compared with other cell lines, MtT/E cells showed stronger IGF-I immunoreactivity. Neutralization of IGF-I with an antihuman IGF-I antibody reduced viability of the cell lines(5).
6. Esophageal cancer
In the study to evaluate the relationship between green tea consumption and the risk of esophageal cancer of the 902 patients interviewed, 734 (81.4%) had their disease pathologically confirmed, showed that All analyses of tea effects were conducted separately among men and women and all were adjusted for age. After further adjustment for other known confounders, a protective effect of green teadrinking on esophageal cancer was observed among women (odds ratio [OR] = 0.50; 95% confidence interval [CI] = 0.30-0.83), and this risk decreased (P for trend < or = .01) as tea consumption increased. Among men, the ORs were also below 1.00, although not statistically significant. ORs for green tea intake were estimated among those persons who neither smoked nor drank alcohol. In this subset, statistically significant decreases in risk among tea drinkers were observed for both men (OR = 0.43; 95% CI = 0.22-0.86; P for trend = .05) and women (OR = 0.40; 95% CI = 0.20-0.77; P for trend < .001)(6).
7. Bowel Cancer (Colon and rectum)
pigallocatechin-3-gallate (EGCG), a major polyphenolic constituent in green tea has been exerted protective effects against proliferation and migration of the human colon cancer SW620 cells. In the study of Epigallocatechin-3-gallate inhibits proliferation and migration of human colon cancer SW620 cells in vitro found that EGCG blocks the proliferation and migration of SW620 cells induced by PAR2-AP and factor VIIa via inhibition of the ERK1/2 and NF-κB pathways. The compound may serve as a preventive and therapeutic agent for colon cancers(7).
8. Cervical Cancer
Phytochemicals present in tea, particularly polyphenols, have anticancer properties against several cancer types. In the study to investigate the mechanism of antiproliferative and apoptotic actions exerted by tea polyphenols on human papilloma virus-18-positive HeLa cervical cancer cells, showed that treatment of green tea polyphenol (-)-epigallocatechin gallate (EGCG) and black tea polyphenol theaflavins (TF) in HeLa cells showed a marked concentration- and time-dependent inhibition of proliferation and induced sub-G1 phase in a dose-dependent manner after 24 h. There was an attenuation of mitochondrial membrane potential with the increase of reactive oxygen species generation, p53 expression, Bax/Bcl-2 ratio, cytochrome-c release, and cleavage of procaspase-3 and -9 and poly(ADP-ribose)-polymerase, indicating the participation of a mitochondria related mechanism. In addition, EGCG as well as TF inhibited activation of Akt and nuclear factor-kappaB (NF-kappaB) via blocking phosphorylation and subsequent degradation of inhibitor of kappaBalpha and kappaBbeta subunits, thereby downregulating cyclooxygenase-2(8).
Flavonoid quercetin found abundantly in green and black tea are associated with cell proliferation and apoptosis. Dr Vidya Priyadarsini R, and the research team at the Annamalai University, in the study of The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition, indicated that quercetin suppressed the viability of HeLa cells in a dose-dependent manner by inducing G2/M phase cell cycle arrest and mitochondrial apoptosis through a p53-dependent mechanism. This involved characteristic changes in nuclear morphology, phosphatidylserine externalization, mitochondrial membrane depolarization, modulation of cell cycle regulatory proteins and NF-κB family members, upregulation of proapoptotic Bcl-2 family proteins, cytochrome C, Apaf-1 and caspases, and downregulation of antiapoptotic Bcl-2 proteins and survivin(8a)
9. Endometrial cancer
In the study to investigate the interactive effect of polymorphisms in the sex hormone-binding globulin (SHBG) gene with soy isoflavones, tea consumption, and dietary fiber on endometrial cancer risk in a population-based, case-control study of 1,199 endometrial cancer patients and 1,212 controls, found that the Asp(327)Asn (rs6259) polymorphism was associated with decreased risk of endometrial cancer, particularly among postmenopausal women (OR = 0.79, 95% CI = 0.62-1.00). This single nucleotide polymorphism (SNP) modified associations of soy isoflavones and tea consumption but not fiber intake with endometrial cancer, with the inverse association of soy intake and tea consumption being more evident for those with the Asp/Asp genotype of the SHBG gene at Asp(327)Asn (rs6259), particularly premenopausal women (P(interaction) = 0.06 and 0.02, respectively, for soyisoflavones and tea intake)(9).
10. Hodgkin's lymphoma
Epigallocatechin-3-gallate (EGCG), a phytochemicals found abundantly in green tea has enhanced the protective effects against Lymphoma. Dr, Yu AF, and scientists at the Fujian Medical University,in the study of [Demethylation and transcription of p16 gene in malignant lymphoma cell line CA46 induced by EGCG], found that after treatment with EGCG for 48 hours, the methylation level was apparently attenuated in a concentration-dependent manner. Expression of p16 gene in untreated group was mild while in the treated groups it had been greatly strengthened, as compared with untreated group, the gray scale ratio of p16 to beta-actin 1 treated with EGCG (6, 12, 24) microg/ml was increased from (0.05 +/- 0. 01) to (0.19 +/- 0.03), (0.39 +/- 0.10), (0.85 +/- 0.09) respectively, exhibiting a significant difference (p < 0.05); as compared with the untreated group, after treatment with EGCG for 48 hours, the expressions of DNMT3A and DNMT3B were obviously down-regulated. It is concluded that EGCG can activate and up-regulate the expression of p16 gene mRNA which inhibits the proliferation of CA46 cell through inducing the G(0)/G(1) arrest by demethylation and/or by inhibiting DNMT3A and DNMT3B gene(10).
11. Kaposi's sarcoma
In the study to investigate the effects of green tea and epigallocatechin-3-gallate (EGCG) tested in a highly vascular Kaposi's sarcoma (KS) tumor model and on endothelial cells in a panel of in vivo and in vitro assays, showed that EGCG inhibited KS-IMM cell growth and endothelial cell growth, chemotaxis, and invasion over a range of doses; high concentrations also induced tumor cell apoptosis. EGCG inhibited the metalloprotease-mediated gelatinolytic activity produced by endothelial cell supernatants and the formation of new capillary-like structures in vitro. Green tea or purified EGCG when administered to mice in the drinking water inhibited angiogenesis in vivo in the Matrigel sponge model and restrained KS tumor growth(11).
12. Renal cell carcinoma (Kidney cancer/renal cells)
EGCG (epigallocatechin gallate) is a phytochemical found in green tea has showed to protect against the proliferation of renal cell carcinoma. "Before and after EGCG treatment, real-time methylation specific PCR could not detect methylation status of TFPI-2 gene promoter in cell line 786-0. In vivo invasiveness and metastasis test did not indicate any significant differences between control and treatment group. Our results suggest that EGCG inhibits growth and induces apoptosis in renal cell carcinoma through TFPI-2 overexpression. This is the first report showing that EGCG is likely to be an effective agent for renal cell carcinoma" said scientists at the Shanghai Medical College, Fudan University(12).
13. Ovarian cancer
a. In prospective cohort study to investigate whether tea consumption can enhance the survival of patients with epithelial ovarian cancer conducted in Hangzhou, China, found that Compared to non-drinkers, the adjusted hazard ratios were 0.55 (95% CI = 0.34-0.90) for tea-drinkers, 0.43 (95% CI = 0.20-0.92) for consuming at least 1 cup of green tea/day, 0.44 (95% CI = 0.22-0.90) for brewing 1 batch or more of green tea/day, 0.40 (95% CI = 0.18-0.90) for consuming more than 500 g of dried tea leaves/year, and 0.38 (95% CI = 0.15-0.97) for consuming at least 2 g of dried tea leaves/batch. The corresponding dose-response relationships were significant (p < 0.05)(13).
b. Other suggested that studies on the health benefits of drinking tea, particularlygreen tea, are finding exciting results, particularly in cancer research. Modern studies in both Asia and the West have provided encouraging results indicating that drinking green tea contributes to fighting many different kinds of cancers including stomach, oesophageal, ovarian and colon(13a).
14. Thyroid cancer
Epigallocatechin-3-gallate (EGCG), a major catechin in green tea, was shown to possess remarkable therapeutic potential against various types of human cancercells in in vitro and in vivo models. In the study to investigate the effect of EGCG on the proliferation and apoptosis of ARO cells--human ATC cells, showed that EGCG treatment inhibited the growth of ARO cells in a dose-dependent manner. Furthermore, EGCG suppressed phosphorylation of EGFR, ERK1/2, JNK, and p38. These changes were associated with increased p21 and reduced cyclin B1/CDK1 expression. In addition, EGCG treatment increased the accumulation of sub-G1 cell, activated caspase-3 and cleaved PARP(14).
15. Testicle cancer
on human testicular cancer cell line NT 2/DT matrigel invasion and MMP activity, showed that The nutrient mixture showed no significant effect on testis cancer cell growth. Zymography demonstrated secretion of MMP-2 by untreated human testiscancer cells and MMP-9 with PMA induction. NM inhibited secretion of both MMPs in a dose-dependent fashion with virtual total inhibition of MMP-9 at 100 microg/mL. Invasion of human testis cancer cells through Matrigel was reduced by 84% at 50 microg/mL and at 100 microg/mL (p = 0.004). NM significantly inhibited MMP secretion and matrix invasion in testicular cancer cells without toxic effect, indicating potential as an anticancer agent(15)
16. Skin Cancer
In the investigations and mechanistic studies that define and support the photoprotective efficacy of green tea polyphenols (GTPs) against UV carcinogenesis, showed that oral administration of GTPs in drinking water or the topical application of EGCG prevents UVB-induced skin tumor development in mice, and this prevention is mediated through: (a) the induction of immunoregulatory cytokine interleukin (IL) 12; (b) IL-12-dependent DNA repair following nucleotide excision repair mechanism; (c) the inhibition of UV-induced immunosuppression through IL-12-dependent DNA repair; (d) the inhibition of angiogenic factors; and (e) the stimulation of cytotoxic T cells in a tumor microenvironment(16).
17. Prostate cancers
Tea polyphenols have been extensively studied in cell culture and animal models where they inhibited tumor onset and progression. "In vivo animal, and clinical intervention studies examine the effects of extracts of GT or purified (-)-epigallocatechin-3-gallate (EGCG) on prostate carcinogenesis. These studies provide strong evidence supporting a chemopreventive effect of GT, but results from epidemiological studies of GT consumption are mixed. While the evidence for a chemopreventive effect of BT is much weaker than the body of evidence with regard to GT, there are several animal BT intervention studies demonstrating inhibition of CaP growth" said Dr. Henning SM, and the research team at the University of California(17)
18. Pharynx Cancer or pharyngeal cancer
In a study of a total of 20,550 men and 29,671 women aged 40-79 years, without any history of oral and pharyngeal cancer showed that for women, the HRs of oralcancer for green tea consumption of 1-2, 3-4, and 5 or more cups per day were 0.51 (95% CI: 0.10-2.68), 0.60 (95% CI: 0.17-2.10), and 0.31 (95% CI: 0.09-1.07), respectively, compared with those who drank less than one cup per day (p for trend, 0.08). For men, no such trends were observed(18).
19. Multiple myeloma (Myeloma)
(-)-epigallocatechin-3-gallate extracted from green tea have exerted the inhibitory effect against multiple myeloma cells. Dr. Shammas MA and the research team at Veterans Administration Boston Health Care System, and Dana Farber Cancer Institute/Harvard Medical School, showed that EGCG interacts with the 67-kDa laminin receptor 1 (LR1), which is significantly elevated in myeloma cell lines and patient samples relative to normal PBMCs. RNAi-mediated inhibition of LR1 resulted in abrogation of EGCG-induced apoptosis in myeloma cells, indicating that LR1 plays an important role in mediating EGCG activity in MM while sparing PBMCs. Evaluation of changes in gene expression profile indicates that EGCG treatment activates distinct pathways of growth arrest and apoptosis in MM cells by inducing the expression of death-associated protein kinase 2, the initiators and mediators of death receptor-dependent apoptosis (Fas ligand, Fas, and caspase 4), p53-like proteins (p73, p63), positive regulators of apoptosis and NF-kappaB activation (CARD10, CARD14), and cyclin-dependent kinase inhibitors (p16 and p18)(19).
20. Oral cancer
Green tea is important source of polyphenol antioxidants. Polyphenols including epigallocatechin 3 gallate (EGCG) constitute the most interesting components ingreen tea leaves. Green tea has the potential to protect against various malignant, cardiovascular and metabolic diseases. Dr. Narotzki B and the research team at the Technion-Israel Institute of Technology, indicated that Green tea protects against bacterial induced dental caries. Tea polyphenols possess antiviral properties, believed to help in protection from influenza virus. Additionally, greentea polyphenols can abolish halitosis through modification of odorant sulphur components. Oral cavity oxidative stress and inflammation, consequent to cigarette smoking and cigarettes' deleterious compounds nicotine and acrolein, may be reduced in the presence of green tea polyphenols. Generally, green tea defends healthy cells from malignant transformation and locally has the ability to induce apoptosis in oral cancer cells(20).
21. Melanoma skin cancer
In the study to determine the effect of green tea catechins on the invasive potential of human melanoma cells and the molecular mechanisms underlying these effects using A375 (BRAF-mutated) and Hs294t (Non-BRAF-mutated) melanoma cell lines as an in vitro model, showed that EGCG, a major green tea catechin, has the ability to inhibit melanoma cell invasion/migration, an essential step of metastasis, by targeting the endogenous expression of COX-2, PGE(2) receptors and epithelial-to-mesenchymal transition(21).
22. Non-Hodgkin's Lymphoma
(-)-Epigallocatechin-3-gallate (EGCG), a major constituent of green teapolyphenols in green tea, has been shown to suppress cancer cell proliferation and induce apoptosis.In the study to investigate its efficacy and the mechanism underlying its effect using human B lymphoblastoid cell line Ramos, and effect of co-treatment with EGCG and a chemotherapeutic agent on apoptotic cell death found that pretreatment with diphenylene iodonium chloride, an inhibitor of NAD(P)H oxidase and an antioxidant, partially suppressed both EGCG-induced apoptosis and production of ROS, implying that oxidative stress is involved in the apoptotic response. Furthermore, we showed that combined-treatment with EGCG and a chemotherapeutic agent, etoposide, synergistically induced apoptosis in Ramos cells(22).
In the study to investigate the association between green tea consumption andleukemia, Dr. Kuo YC, and scientists at the Harvard School of Public Health, indicated that a significant inverse association between green tea consumption andleukemia risk was found in individuals aged 16-29 years, whereas no significant association was found in the younger age groups. For the older group with higher amounts of tea consumption (>550 units of catechins), the adjusted odds ratio (OR) compared with the group without tea consumption was 0.47 [95% confidence interval (CI) = 0.23-0.97]. After we adjusted for smoking status and medical irradiation exposure, the overall OR for all participants was 0.49 (95% CI = 0.27-0.91), indicating an inverse relation between large amounts of catechins andleukemia(23).
24. Larynx Cancer or Laryngeal Cancer
In the study to evaluated the potential cytotoxic and prooxidative effects of green tea extract and its two main flavonoid constituents epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) on human laryngeal carcinoma cell line (HEp2) and its cross-resistant cell line CK2, showed that EGCG and green tea extract increased the DNA damage in the CK2 cell line during short exposure. The cytotoxicity of EGCG and ECG increased with the time of incubation. Green tea extract induced lipid peroxidation in the CK2 cell line(24).
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