Clinical References - Cell Health Recovery
1. Stohs SJ., J Basic Clin Physiol Pharmacol 1995;6(3-4):205-28
The role of free radicals in toxicity and disease.
Oxidative stress associated with production of reactive oxygen species is believed to be involved not only in the toxicity of xenobiotics but also in the pathophysiology of aging, and various age-related diseases, including cataracts, atherosclerosis, neoplastic diseases, diabetes, diabetic retinopathy, chronic inflammatory diseases of the gastrointestinal tract, aging of skin, diseases associated with cartilage, Alzheimer's disease, and other neurological disorders.
2. Jaeschke H, et al, Toxicol Sci 2002 Feb;65(2):166-176
Because of its unique metabolism and relationship to the gastrointestinal tract, the liver is an important target of the toxicity of drugs, xenobiotics, and oxidative stress.
3. Sen CK., Sports Med 2001;31(13):891-908
Studies during the past 2 decades suggest that during strenuous exercise, generation of reactive oxygen species (ROS) is elevated to a level that overwhelms tissue antioxidant defence systems. The result is oxidative stress. Although excessive oxidants may cause damage to tissues, lower levels of oxidants in biological cells may act as messenger molecules enabling the function of numerous physiological processes.
4. Lin JK, Chen PC, Ho CT, Lin-Shiau SY., J Agric Food Chem 2000 Jul;48(7):2736-43.
Inhibition of xanthine oxidase and suppression of intracellular reactive oxygen species in HL-60 cells by theaflavin-3,3'-digallate, (-)-epigallocatechin-3-gallate, and propyl gallate. The antioxidative activity of polyphenols and PG is due not only to their ability to scavenge superoxides but also to their ability to block XO and related oxidative signal transducers.
5. Droge W. free radicals in the physiological control of cell function. Physiol Rev 2002 Jan; 82(1):47-95
Division of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
6. Vaziri ND, et al, Hypertension 2002 Jan;39(1):135-41
Enhanced nitric oxide inactivation and protein nitration by reactive oxygen species in renal insufficiency. Reactive oxygen species (ROS) avidly reacts with nitric oxide (NO) producing cytotoxic reactive nitrogen species capable of nitrating proteins and damaging other molecules.
7. Gillery P, Monboisse JC, Maquart FX, Borel JP, Med Hypotheses 1989 May; 29(1):47-50. Does oxygen free radical increased formation explain long term complications of diabetes mellitus? Oxygen free radicals (OFR) can form by reaction of glycated proteins with molecular oxygen. The most significant complications of diabetes, for example polyneuritis, retinopathy, microangiopathy, perforating ulcers, impaired healing, may depend on the excessive production of OFR by glycated proteins.
8. Lalazar A, et al, Gene 1997 Aug 22;195(2):235-43
Activation of mesenchymal cells is a central event in the wound healing response of most tissues.
9. Hildebrand KA, Frank CB, Can J Surg 1998 Dec; 41(6):425-9
Scar formation and ligament healing. Injuries to ligaments induce a healing response that is characterized by the formation of a scar. The scar tissue is weaker, larger and creeps more than normal ligament and is associated with an increased amount of minor collagens (types III, V and VI), decreased collagen cross-links and an increased amount of glycosaminoglycans.
10. Monboisse JC, Borel JP, EXS 1992; 62:323-7. Oxidative damage to collagen.
Extracellular matrix molecules, such as collagens, are good targets for oxygen free radicals. Collagen is the only protein susceptible to fragmentation by superoxide anion as demonstrated by the liberation of small 4-hydroxyproline-containing-peptides.
11. Roughley P J, Mort J S. Aging and the aggregating proteoglycans of human articular cartilage. Clinical Science 1986; 71: 337-44.
With increasing age, there is an overall decrease in long-chain glycosaminoglycan production and an increase in shorter chain glycosaminoglycan production.
12. Nerlich AG, et al, Virchows Arch 1998 Jan; 432(1):67-76
Immunolocalization of major interstitial collagen types in human lumbar intervertebral discs of various ages. Collagens III and VI were significantly increased in areas of minor to advanced degeneration in all anatomical settings, while collagen V showed only minor changes in its staining pattern. In general, histological signs of tissue degeneration coincided with significant quantitative, but also with certain qualitative, changes in the composition of the collagenous disc matrix.
13. Rizvi SI, J Physiol Pharmacol 2001 Sep;52(3):483-8
Intracellular reduced glutathione content in normal and type 2 diabetic erythrocytes: effect of insulin and (-)epicatechin. A higher content of dietary flavanoids may thus protect diabetic patients against long-term complications.
14. Rizvi SI, Clin Exp Pharmacol Physiol 2001 Sep;28(9):776-8
Insulin-like effect of (-)epicatechin on erythrocyte membrane acetylcholinesterase activity in type 2 diabetes mellitus.
15. Bradley JL, et al, Acta Neuropathol (Berl) 2000 May; 99(5):539-46
The extracellular matrix of peripheral nerve in diabetic polyneuropathy.
16. Barnes M J. Collagens in atherosclerosis. Collagen and related research 1985; 5: 65-97.
Type V and VI collagens are increased in atherosclerotic plaques.
17. Hibbs M S, Hoidal J R, Kang A H. Expression of a metalloproteinase that degrades native type V collagen and denatured collagens by cultured alveolar macrophages. Journal of Clinical Investigation 1987; 80: 1644-50
Glycosylation increases with age and leads to increased stable crosslinking.
18. Mohan P S, Carter W G, Spiro R G. Occurrence of type VI collagen in extracellular matrix of renal glomerulus and its increase in diabetes. Diabetes 1990; 39: 31-7.
Type VI collagen is seen most prominently in pathological situations.
19. Narayanan A S, Page R C. Synthesis of type V collagen by fibroblasts derived from normal, inflamed and hyperplastic human connective tissues. Collagen and Related Research 1985; 5: 297-304
An increased content of type V collagen is apparent in inflammatory and proliferative disease, hypertrophic scars and carcinomata.
20. Hillmann G, et al, Clin Oral Investig 2001 Dec; 5(4):227-35
Immunohistological and morphometric analysis of inflammatory cells in rapidly progressive periodontitis and adult periodontitis. At baseline, the inflamed gingival tissue consists mainly of collagen types V and VI in areas with infiltrates of inflammatory cells.
21. Primorac D, et al, Croat Med J 2001 Aug; 42(4):393-415
Osteogenesis imperfecta (OI), or brittle bone disease, is a heritable disorder characterized by increased bone fragility. In most cases, there is a reduction in the production of normal type I collagen or the synthesis of abnormal collagen as a result of mutations in the type I collagen genes.
22. Kitamura M, et al, Clin Cardiol 2001 Apr; 24(4):325-9
Collagen remodelling and cardiac dysfunction in patients with hypertrophic cardiomyopathy: the significance of type III and VI collagens.
23. CORA TABAK, et al, Am. J. Respir. Crit. Care Med., Volume 164, Number 1, July 2001, 61-64
Chronic Obstructive Pulmonary Disease and Intake of Catechins, Flavonols, and Flavones The MORGEN Study
24. Karran EH, et al, Ann Rheum Dis 1995 Aug; 54(8):662-9
An in vivo model of cartilage degradation that permits the measurement of proteoglycan and collagen in both non-calcified articular cartilage and calcified cartilage compartments.
25. Paquay JB, et al, J Agric Food Chem 2000 Nov;48(11):5768-72
It is found that catechins are able to protect against nitric oxide (NO(*)) toxicity in several ways.
26. Rao CN, Rao VH, Steinmann B., Scand J Rheumatol 1983; 12(1):39-42. Bioflavonoid-mediated stabilization of collagen in adjuvant-induced arthritis. In rats with adjuvant-induced arthritis, the effect of (+)-catechin (CA)) on the cross linking of collagen was studied. All results may collectively indicate that catechins promote the cross linking of collagen in arthritic animals.
27. Rao CN, Rao VH, Steinmann B., Ital J Biochem 1981 Jul-Aug; 30(4):259-70. Influence of bioflavonoids on the metabolism and cross linking of collagen. The results of the present study indicate that the synthesis of collagen is unaffected, the cross linking of collagen is promoted and the degradation of soluble collagen is decreased in the bioflavonoids treated groups.
28. Matteucci E, Cell Biol Int 2001;25(8):771-6
Studies show erythrocyte sodium/hydrogen exchange inhibition by (-) epicatechin could be one of the major mechanisms underlying the antiproliferative effects of catechins.
29. Aucamp J, et al, Anticancer Res 1997 Nov-Dec;17(6D):4381-5
Inhibition of xanthine oxidase by catechins.
The liver enzyme, xanthine oxidase (XO) produces uric acid and reactive oxygen species (ROS) during the catabolism of purines. Excess of the former can lead to gout and of the latter to increased oxidative stress and mutagenesis.
30. Rao CN, Rao VH, Verbruggen L, Orloff S., Scand J Rheumatol 1980;9(4):280-4. Effect of bioflavonoids on lysosomal acid hydrolases and lysosomal stability in adjuvant-induced arthritis.
Results demonstrate the fragility of lysosomes in arthritic tissues. Administration of CA or HR to the arthritic animals was found to have a prophylactic action by stabilizing liver lysosomes and reducing the free lysosomal enzyme activities in serum, liver, kidney and spleen. CA was more effective than HR
31. Yu-Li Lin, MOLECULAR PHARMACOLOGY 52:465-472 (1997).
Epigallocatechin-3-gallate Blocks the Induction of Nitric Oxide Synthase by Down-Regulating Lipopolysaccharide-Induced Activity of Transcription Factor Nuclear Factor- B. Nitric oxide (NO) plays an important role in inflammation and multiple stages of carcinogenesis.
32. L Liu, Carcinogenesis, Vol 12, 1203-1208, 1991.
Catechin could inhibit the metabolism and DNA damage induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco- specific carcinogen.
Results demonstrate that (+)-catechin inhibits the formation of DNA-damaging intermediates by selectively impairing the enzymatic activation of NNK. They suggest that (+)-catechin could be an effective preventive agent against NNK hepatocarcinogenicity.
33. Chan MM, et al, Biochem Pharmacol 1997 Dec 15;54(12):1281-6
Inhibition of inducible nitric oxide synthase gene expression and enzyme activity by epigallocatechin gallate.
Chronic inflammation has been implicated as the underlying factor in the pathogenesis of many disorders.
34. Sazuka M, et al, Biosci Biotechnology Biochem 1997 Sep;61(9):1504-6
Inhibition of collagenases from mouse lung carcinoma cells by catechins.
Results suggest that (-)-epigallocatechin gallate inhibit tumor cell invasion by inhibiting type IV collagenases of the LL2-Lu3 cells.
35. Monboisse JC, Braquet P, Randoux A, Borel JP, Biochem Pharmacol 1983 Jan 1; 32(1):53-8. Non-enzymatic degradation of acid-soluble calf skin collagen by superoxide ion: protective effect of flavonoids. This work confirms that collagen may be degraded during the process of inflammation and that some flavonoids are endowed with protective properties.
36. Nakagawa K, et al, J Agric Food Chem 1999 Oct;47(10):3967-73
Catechin supplementation increases antioxidant capacity and prevents phospholipid hydroperoxidation in plasma of humans.
37. Spencer JP, et al, Antioxid Redox Signal 2001 Dec;3(6):1023-39
Bioavailability of flavan-3-ols and procyanidins: gastrointestinal tract influences and their relevance to bioactive forms in vivo. Studies suggest that the major bioactive forms of flavanol monomers and procyanidins in vivo are likely to be metabolites and/or conjugates of epicatechin. One such metabolite, 3'-O-methylepicatechin, has been shown to exert protective effects against oxidative stress-induced cell death.
38. Hara Y., J Cell Biochem Suppl 1997;27:52-8
Influence of tea catechins on the digestive tract.
The bactericidal property of catechins plays several roles in the digestive tract. In the small intestine, catechins inhibit alpha-amylase activity, and a certain amount is absorbed into the portal vein. Although catechins are bactericidal, they do not affect lactic acid bacteria.
39. Murakami S, et al, J Pharm Pharmacol 1992 Nov;44(11):926-8
Five catechins, (+)-catechin, (-)-epicatechin, (-)-epicatechin gallate, (-)-epigallocatechin and (-)-epigallocatechin gallate, inhibited gastric H+, K(+)-ATPase activity. These findings suggest that the anti-secretory and anti-ulcerogenic effects of catechins previously reported, are due to their inhibitory activity on gastric H+, K(+)-ATPase.
40. Hassan A, et al, Methods Find Exp Clin Pharmacol 1998 Dec;20(10):849-54
Role of antioxidants in gastric mucosal damage induced by indomethacin in rats.
These results suggest that like plasma, the gastric mucosa has an antioxidant capacity and only when this capacity is exhausted are the lesive effects of the oxygen free radicals manifested.
41. Somasundaram R, et al, J Biol Chem 2000 Dec 8; 275(49):38170-5
Collagens serve as an extracellular store of bioactive interleukin 2. The binding of certain growth factors and cytokines to components of the extracellular matrix can regulate their local availability and modulate their biological activities.
42. Bensadoun ES, et al, Eur Respir J 1997 Dec; 10(12):2731-7
Proteoglycans in granulomatous lung diseases. In this study, we examined the localization of proteoglycans and collagen in the granulomatous lung conditions, sarcoidosis, extrinsic allergic alveolitis (EAA) and tuberculosis (TB).
43. Kajiya K, Biosci Biotechnology Biochem 2001 Dec;65(12):2638-43
Steric effects on interaction of catechins with lipid bilayers. Trans-type catechins with the galloyl moiety were located on the surface of the lipid bilayer, as well as cis-type catechins with the galloyl moiety, and perturbed the membrane structure.
44. Tsuchiya H., Chem Biol Interact 2001 Mar 14;134(1):41-54
Stereospecificity in membrane effects of catechins.
. At lower concentrations (5-100 microM), (-)-epigallocatechin gallate and (-)-epicatechin gallate reduced membrane fluidity more significantly than (-)-epicatechin, suggesting that the intensive membrane effect contributes to the potent medicinal utility of (-)-epigallocatechin gallate.
45. Nagasawa T, et al, Biosci Biotechnol Biochem 2000 May;64(5):1004-10
The results of this study show that the antioxidative property of EGCg was effective for suppressing oxidative modification of the skeletal muscle protein induced by electrical stimulation. This finding demonstrates that EGCg has a beneficial effect in vivo on the free radical-mediated oxidative damage to muscle proteins.
46. Erba D., et al, Journal of Nutrition. 1999;129:2130-2134
Observed protective effects can be attributed to epigallocatechin gallate and we cannot exclude contributions by other catechins. These data support a protective effect against oxidative damage.
47. Rao CN, Rao VH, Ital J Biochem 1980 Mar-Apr; 29(2):89-101. Effect of bioflavonoids on the urinary excretion of hydroxyproline, hydroxylysyl glycosides and hexosamine in adjuvant arthritis.
The effects of (+)--Catechin (AC) and 0--(beta hydroxyethyl) rutosides (HR) on the urinary collagen metabolites were studied up to 49 days in rats with adjuvant-induced arthritis. The elevated levels of urinary total, non-dialysable and dialysable hydroxyproline, hydroxylysyl glycosides and total hexosamine in the arthritic animals were found to be slightly decreased in the acute phase and significantly decreased in the chronic phase of the disease due to the administration of bioflavonoids. Of the two bioflavonoids tests, CA was found to afford more protective action than HR.
48. Nakayama T, et al, Biofactors 2000;13(1-4):147-51
Interaction of catechins with lipid bilayers has been investigated with liposome systems. Epicatechin gallate had the highest affinity for lipid bilayers, followed by epigallocatechin gallate, epicatechin, and epigallocatechin. Epicatechin gallate and epigallocatechin gallate in the surface of lipid bilayer perturbed the membrane structure.
49. Yang B, Chem Pharm Bull (Tokyo) 2001 Jun;49(6):747-51
Relationship of electrochemical oxidation of catechins on their antioxidant activity in microsomal lipid peroxidation.
This relationship suggested two important characteristics determining catechin antioxidant activity, namely the ease of oxidation and the lipophilicity.
50. Shi X, et al, Mol Cell Biochem 2000 Mar;206(1-2):125-32
EGCG efficiently scavenges *OH radicals with reaction rate of 4.62 x 10(11) M(-1)sec(-1), which is an order of magnitude higher than several well recognized antioxidants, such as ascorbate, glutathione and cysteine. It also scavenges O2*-radicals as demonstrated by using xanthine and xanthine oxidase system as a source of O2*- radicals. Through its antioxidant properties, EGCG exhibited a protective effect against DNA damage induced by Cr(VI).
Singh R, Ahmed S, Malemud CJ, Goldberg VM, Haqqi TM, J Orthop Res 2003 Jan;21(1):102-9 Epigallocatechin-3-gallate selectively inhibits interleukin-1beta-induced activation of mitogen activated protein kinase subgroup c-Jun N-terminal kinase in human osteoarthritis chondrocytes.
Clinical References - Osteoarthritis Recovery
1. Singh R, Ahmed S, Malemud CJ, Goldberg VM, Haqqi TM, J Orthop Res 2003 Jan;21(1):102-9
Epigallocatechin-3-gallate selectively inhibits interleukin-1beta-induced activation of mitogen activated protein kinase subgroup c-Jun N-terminal kinase in human osteoarthritis chondrocytes.
Activation of mitogen activated protein kinases (MAPK) is a critical event in pro-inflammatory cytokine-induced signalling cascade in synoviocytes and chondrocytes that lead to the production of several mediators of cartilage damage in an arthritic joint. Green tea (Camellia sinensis) is a widely consumed beverage and we earlier showed that polyphenols present in green tea (GTP) inhibit the development of inflammation and cartilage damage in an animal model of arthritis. In this study we evaluated the role of epigallocatechin-3-gallate (EGCG), a green tea polyphenol which mimics its anti-inflammatory effects, in modulating the IL-1beta-induced activation of MAPK's in human chondrocytes. We discovered that EGCG inhibited the IL-1beta-induced phosphorylation of c-Jun N-terminal kinase (JNK) isoforms, accumulation of phospho-c-Jun and DNA binding activity of AP-1 in osteoarthritis (OA) chondrocytes. Also IL-1beta, but not EGCG, induced the expression of JNK p46 without modulating the expression of JNK p54 in OA chondrocytes. In immunocomplex kinase assays, EGCG completely blocked the substrate phosphorylating activity of JNK but not of p38-MAPK. EGCG had no inhibitory effect on the activation of extracellular signal-regulated kinase p44/p42 (ERKp44/p42) or p38-MAPK in OA chondrocytes. EGCG or IL-1beta did not alter the total non-phosphorylated levels of either p38-MAPK or ERKp44/p42 in OA chondrocytes. Conclusion: These are novel findings and indicate that EGCG may be of potential benefit in inhibiting IL-1beta-induced catabolic effects in OA chondrocytes that are dependent on JNK activity.
2. Ahmed S, Rahman A, Hasnain A, Lalonde M, Goldberg VM, Haqqi TM, Free Radic Biol Med 2002 Oct 15;33 (8):1097-105
Green tea polyphenol epigallocatechin-3-gallate inhibits the IL-1 beta-induced activity and expression of cyclooxygenase-2 and nitric oxide synthase-2 in human chondrocytes.
We have previously shown that green tea polyphenols inhibit the onset and severity of collagen II-induced arthritis in mice. In the present study, we report the pharmacological effects of green tea polyphenol epigallocatechin-3-gallate (EGCG), on interleukin-1 beta (IL-1 beta)-induced expression and activity of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in human chondrocytes derived from osteoarthritis (OA) cartilage. Stimulation of human chondrocytes with IL-1 beta (5 ng/ml) for 24 h resulted in significantly enhanced production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) when compared to untreated controls (p <.001). Pretreament of human chondrocytes with EGCG showed a dose-dependent inhibition in the production of NO and PGE(2) by 48% and 24%, respectively, and correlated with the inhibition of iNOS and COX-2 activities (p <.005). In addition, IL-1 beta-induced expression of iNOS and COX-2 was also markedly inhibited in human chondrocytes pretreated with EGCG (p <.001). Parallel to these findings, EGCG also inhibited the IL-1 beta-induced LDH release in chondrocytes cultures. Conclusion: Overall, the study suggests that EGCG affords protection against IL-1 beta-induced production of catabolic mediators NO and PGE (2) in human chondrocytes by regulating the expression and catalytic activity of their respective enzymes. Furthermore, our results also indicate that ECGC may be of potential therapeutic value for inhibiting cartilage resorption in arthritic joints.
3. Singh R, Ahmed S, Islam N, Goldberg VM, Haqqi TM, Arthritis Rheum 2002 Aug; 46 (8):2079-86
Epigallocatechin gallate inhibits interleukin-1beta-induced expression of nitric oxide synthase and production of nitric oxide in human chondrocytes: suppression of nuclear factor kappaB activation by degradation of the inhibitor of nuclear factor kappaB.
Human chondrocytes were derived from OA cartilage and were treated with EGCG (100 microM) and IL-1beta (2 ng/ml) for different periods, and inducible nitric oxide synthase (iNOS) messenger RNA and protein expression was determined by real-time quantitative reverse transcriptase-polymerase chain reaction and Western blotting, respectively. Production of NO was determined as nitrite in culture supernatant. Activation and translocation of nuclear factor kappaB (NF-kappaB), levels of inhibitor of nuclear factor kappaB (IkappaB), and NF-kappaB DNA binding activity were determined by Western blotting and a highly sensitive and specific enzyme-linked immunosorbent assay. Activity of IkappaB kinase was determined using in vitro kinase assay. Human chondrocytes cotreated with EGCG produced significantly less NO compared with chondrocytes stimulated with IL-1beta alone (P < 0.005). The inhibition of NO production correlated with the suppression of induction and expression of NF-kappaB-dependent gene iNOS. EGCG inhibited the activation and translocation of NF-kappaB to the nucleus by suppressing the degradation of its inhibitory protein IkappaBalpha in the cytoplasm.
Conclusion: Our results indicate that EGCG inhibits the IL-1beta-induced production of NO in human chondrocytes by interfering with the activation of NF-kappaB through a novel mechanism. Our data further suggest that EGCG may be a therapeutically effective inhibitor of IL-1beta-induced inflammatory effects that are dependent on NF-kappaB activation in human OA chondrocytes.
4. Takita H, Kikuchi M, Sato Y, Kuboki Y, Connect Tissue Res 2002;43(2-3):520-3
Inhibition of BMP-induced ectopic bone formation by an antiangiogenic agent (epigallocatechin gallate)
Epigallocatechin gallate (EGCG), which is one of the components of green tea, was recently shown to inhibit endothelial cell growth in vitro and angiogenesis in vivo [5]. We have previously shown that bone and cartilage formation by bone morphogenetic protein (BMP) is highly dependent on the geometry of the carrier (vasculature-inducing or -inhibiting geometry [2]. To verify the function of angiogenesis in the BMP induction system, we examine in this article whether inhibition of angiogenesis enhances chondrogenesis and suppresses osteogenesis. Fibrous glass membrane used as a BMP carrier was mixed with 1.2 micrograms rhBMP-2 and 1-10 micrograms of EGCG and was implanted into rats subcutaneously. As the dose of EGCG increased, alkaline phosphatase activity and calcium content were decreased, whereas the type II collagen content was increased. Conclusion: The results clearly indicated that inhibition of vascularization enhanced chondrogenesis and suppressed osteogenesis.
5. Chen PC, Wheeler DS, Malhotra V, Odoms K, Denenberg AG, Wong HR, Inflammation 2002 Oct; 26 (5):233-41
A green tea-derived polyphenol, epigallocatechin-3-gallate, inhibits IkappaB kinase activation and IL-8 gene expression in respiratory epithelium.
Interleukin-8 (IL-8) is a principle neutrophil chemoattractant and activator in humans. There is interest in developing novel pharmacological inhibitors of IL-8 gene expression as a means for modulating inflammation in disease states such as acute lung injury. Herein we determined the effects of epigallocatechin-3-gallate (EGCG), a green tea-derived polyphenol, on tumor necrosis factor-alpha (TNF-alpha)-mediated expression of the IL-8 gene in A549 cells. EGCG inhibited TNF-alpha-mediated IL-8 gene expression in a dose response manner, as measured by ELISA and Northern blot analysis. This effect appears to primarily involve inhibition of IL-8 transcription because EGCG inhibited TNF-alpha-mediated activation of the IL-8 promoter in cells transiently transfected with an IL-8 promoter-luciferase reporter plasmid. In addition, EGCG inhibited TNF-alpha-mediated activation of IkappaB kinase and subsequent activation of the IkappaB alpha/NF-kappaB pathway. Conclusion: We conclude that EGCG is a potent inhibitor of IL-8 gene expression in vitro. The proximal mechanism of this effect involves, in part, inhibition of IkappaB kinase activation.
6. Adcocks C, Collin P, Buttle DJ, J Nutr 2002 Mar; 132 (3):341-6
Catechins from green tea (Camellia sinensis) inhibit bovine and human cartilage proteoglycan and type II collagen degradation in vitro.
Polyphenolic compounds from green tea have been shown to reduce inflammation in a murine model of inflammatory arthritis, but no studies have been undertaken to investigate whether these compounds are protective to joint tissues. We therefore investigated the effects of catechins found in green tea on cartilage extracellular matrix components using in vitro model systems. Bovine nasal and metacarpophalangeal cartilage as well as human nondiseased, osteoarthritic and rheumatoid cartilage were cultured with and without reagents known to accelerate cartilage matrix breakdown. Individual catechins were added to the cultures and the amount of released proteoglycan and type II collagen was measured by metachromatic assay and inhibition ELISA, respectively. Possible nonspecific or toxic effects of the catechins were assessed by lactate output and proteoglycan synthesis. Catechins, particularly those containing a gallate ester, were effective at micromolar concentrations at inhibiting proteoglycan and type II collagen breakdown. No toxic effects of the catechins were evident. Conclusion: We conclude that some green tea catechins are chondroprotective and that consumption of green tea may be prophylactic for arthritis and may benefit the arthritis patient by reducing inflammation and slowing cartilage breakdown. Further studies will be required to determine whether these compounds access the joint space in sufficient concentration and in a form capable of providing efficacy in vivo.
Clinical References - Diabetes Recovery
1. Anderson RA, Polansky MM. J Agric Food Chem 2002 Nov 20;50(24):7182-6
Epigallocatechin-O-gallate (EGCG) enhances insulin activity.
The most widely known health benefits of tea relate to the polyphenols as the principal active ingredients in protection against oxidative damage and in antibacterial, antiviral, anticarcinogenic, and antimutagenic activities, but polyphenols in tea may also increase insulin activity.
The objective of this study was to determine the insulin-enhancing properties of tea and its components. Tea, as normally consumed, was shown to increase insulin activity >15-fold in vitro in an epididymal fat cell assay. Black, green, and oolong teas but not herbal teas, which are not teas in the traditional sense because they do not contain leaves of Camellia sinensis, were all shown to increase insulin activity. High-performance liquid chromatography fractionation of tea extracts utilizing a Waters Symmetry Prep C18 column showed that the majority of the insulin-potentiating activity for green and oolong teas was due to epigallocatechin gallate. For black tea, the activity was present in several regions of the chromatogram corresponding to, in addition to epigallocatechin gallate, tannins, theaflavins, and other undefined compounds.
Several known compounds found in tea were shown to enhance insulin with the greatest activity due to epigallocatechin gallate followed by epicatechin gallate, tannins, and theaflavins. Caffeine, catechin, and epicatechin displayed insignificant insulin-enhancing activities. Addition of lemon to the tea did not affect the insulin potentiating activity.
Addition of 5 g of 2% milk per cup decreased the insulin-potentiating activity one-third, and addition of 50 g of milk per cup decreased the insulin-potentiating activity approximately 90%. Nondairy creamers and soy milk also decreased the insulin enhancing activity.
These data demonstrate that tea contains in vitro insulin-enhancing activity and the predominant active ingredient is epigallocatechin gallate.
PMID: 12428980 [PubMed - indexed for MEDLINE]
2. M C S, K S, Kuttan R., J Ethnopharmacol 2002 Nov;83(1-2):109-16
Anti-diabetic activity of green tea polyphenols and their role in reducing oxidative stress in experimental diabetes.
An aqueous solution of green tea polyphenols (GTP) was found to inhibit lipid peroxidation (LP), scavenge hydroxyl and superoxide radicals in vitro. Concentration needed for 50% inhibition of superoxide, hydroxyl and LP radicals were 10, 52.5 and 136 micro g/ml, respectively. Administration of GTP (500 mg/kg b.wt.) to normal rats increased glucose tolerance significantly (P<0.005) at 60 min. GTP was also found to reduce serum glucose level in alloxan diabetic rats significantly at a dose level of 100 mg/kg b.wt. Continued daily administration (15 days) of the extract 50, 100 mg/kg b.wt. produced 29 and 44% reduction in the elevated serum glucose level produced by alloxan administration.
Elevated hepatic and renal enzymes produced by alloxan were found to be reduced (P<0.001) by GTP. The serum LP levels which was increased by alloxan and was reduced by significantly (P<0.001) by the administration of 100 mg/kg b.wt. of GTP. Decreased liver glycogen, after alloxan administration showed a significant (P<0.001) increase after GTP treatment. GTP treated group showed increased antioxidant potential as seen from improvements in superoxide dismutase and glutathione levels. However catalase, LP and glutathione peroxidase levels were unchanged.
These results indicate that alterations in the glucose utilizing system and oxidation status in rats increased by alloxan were partially reversed by the administration of the glutamate pyruvate transaminase.
PMID: 12413715 [PubMed - in process]
3. Rhee SJ, Kim MJ, Kwag OG., Asia Pac J Clin Nutr 2002;11(3):232-6
Effects of green tea catechin on prostaglandin synthesis of renal glomerular and renal dysfunction in streptozotocin-induced diabetic rats.
The purpose of the present study was to investigate the effects of green tea catechin on prostaglandin synthesis of renal glomerular and renal dysfunction in rats with streptozotocin-induced diabetes. Sprague-Dawley rats weighing 100 +/- 10 g were randomly assigned to one normal group and three groups with streptozotocin-induced diabetes.
The diabetic groups were classified to a catechin-free diet (DM group), a 0.25% catechin diet (DM-0.25C group) and a 0.5% catechin diet (DM-0.5C group) according to the levels of catechin supplement in their diet. The animals were maintained on an experimental diet for 4 weeks. At this point, they were injected with streptozotocin to induce diabetes. They were killed on the sixth day. The catechin supplementation groups (DM-0.25C, DM-0.SC groups) showed a decrease in thromboxane A2 synthesis but an increase in prostacyclin synthesis, compared to the DM group. The ratio of prostacyclin/thromboxane A2 was 53.3% and 38.1% lower in the DM and DM-0.25C groups, respectively, than in the normal group. The ratio in the DM-0.5C group did not differ from that in the normal group. The glomerular filtration rate in catechin feeding groups (DM-0.25C and DM-0.5C groups) was maintained at the normal level. The urinary beta2-microglobulin content in the DM-0.5C group was significantly lower than that in the normal group. On the sixth day after induction of diabetes, the urinary microalbumin content in the DM, DM-0.25C and DM-0.5C groups had increased 5.40, 4.02, 3.87 times, respectively, compared with the normal group.
In conclusion, kidney function appears to be improved by green tea catechin supplementation due to its antithrombotic action, which in turn controls the arachidonic acid cascade system.
PMID: 12230238 [PubMed - in process]
4. Waltner-Law ME, Wang XL, Law BK, Hall RK, Nawano M, Granner DK., J Biol Chem 2002 Sep 20;277(38):34933-40
Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production.
Herbs have been used for medicinal purposes, including the treatment of diabetes, for centuries. Plants containing flavonoids are used to treat diabetes in Indian medicine and the green tea flavonoid, epigallocatechin gallate (EGCG), is reported to have glucose-lowering effects in animals.
We show here that the regulation of hepatic glucose production is decreased by EGCG. Furthermore, like insulin, EGCG increases tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1), and it reduces phosphoenolpyruvate carboxykinase gene expression in a phosphoinositide 3-kinase-dependent manner. EGCG also mimics insulin by increasing phosphoinositide 3-kinase, mitogen-activated protein kinase, and p70(s6k) activity. EGCG differs from insulin, however, in that it affects several insulin-activated kinases with slower kinetics. Furthermore, EGCG regulates genes that encode gluconeogenic enzymes and protein-tyrosine phosphorylation by modulating the redox state of the cell.
These results demonstrate that changes in the redox state may have beneficial effects for the treatment of diabetes and suggest a potential role for EGCG, or derivatives, as an antidiabetic agent.
PMID: 12118006 [PubMed - indexed for MEDLINE]
5. Liao S., Hong Kong Med J 2001 Dec;7(4):369-74
The medicinal action of androgens and green tea epigallocatechin gallate.
Unorthodox (non-traditional or alternative) medicinal practices have been expanding very rapidly in western countries. Modern physicians, scientists, and non-traditional medicine practitioners now must join forces to promote evidence-based medicine to benefit patients. Green tea extracts are among the most widely used ancient medicinal agents, while androgens are probably the oldest drugs used in a purified form in traditional Chinese medicine.
It is now clear that a specific green tea catechin, (-)epigallocatechin-3-gallate, can modulate the production and biological actions of androgens and other hormones.
Modulation of androgenic activity and administration of (-)epigallocatechin-3-gallate may be useful for the treatment of various hormone-related abnormalities, such as benign prostatic hyperplasia, baldness, and acne. (-)Epigallocatechin-3-gallate has also been shown to modulate appetite and control obesity in animals. Publication Types: Review, Tutorial PMID: 11773671 [PubMed - indexed for MEDLINE]
6. Han MK., Exp Mol Med 2003 Apr 30;35(2):136-9
Epigallocatechin gallate, a constituent of green tea, suppresses cytokine-induced pancreatic beta-cell damage.
Cytokines produced by immune cells infiltrating pancreatic islets have been implicated as one of the important mediators of beta-cell destruction in insulin-dependent diabetes mellitus. In this study, the protective effects of epigallocatechin gallate (EGCG) on cytokine-induced beta-cell destruction were investigated. EGCG effectively protected IL-1beta and IFN-gamma-mediated cytotoxicity in insulinoma cell line (RINm5F). EGCG induced a significant reduction in IL-1beta and IFN-gamma-induced nitric oxide (NO) production and reduced levels of the inducible form of NO synthase (iNOS) mRNA and protein levels on RINm5F cells. The molecular mechanism by which EGCG inhibited iNOS gene expression appeared to involve the inhibition of NF-kappaB activation.
These findings revealed EGCG as a possible therapeutic agent for the prevention of diabetes mellitus progression.
PMID: 12754418 [PubMed - in process]
Clinical References - Lung Recovery
1. Dona M, Dell'Aica I, Calabrese F, Benelli R, Morini M, Albini A, Garbisa S.J Immunol. 2003 Apr 15;170(8):4335-41.
Neutrophil restraint by green tea: inhibition of inflammation, associated angiogenesis, and pulmonary fibrosis.
Neutrophils play an essential role in host defense and inflammation, but the latter may trigger and sustain the pathogenesis of a range of acute and chronic diseases. Green tea has been claimed to exert anti-inflammatory properties through unknown molecular mechanisms. We have previously shown that the most abundant catechin of green tea, (-)epigallocatechin-3-gallate (EGCG), strongly inhibits neutrophil elastase.
Here we show that 1) micromolar EGCG represses reactive oxygen species activity and inhibits apoptosis of activated neutrophils, and 2) dramatically inhibits chemokine-induced neutrophil chemotaxis in vitro; 3) both oral EGCG and green tea extract block neutrophil-mediated angiogenesis in vivo in an inflammatory angiogenesis model, and 4) oral administration of green tea extract enhances resolution in a pulmonary inflammation model, significantly reducing consequent fibrosis.
These results provide molecular and cellular insights into the claimed beneficial properties of green tea and indicate that EGCG is a potent anti-inflammatory compound with therapeutic potential.
PMID: 12682270 [PubMed - indexed for MEDLINE]
Biostructural® Medicine goes beyond simply addressing symptoms and focuses on the degenerative process and optimal healing.
Nutricol® (Recovery®) may be safely combined with other medications or taken on its own to help counter inflammation and improve the quality and rate of healing.
Information for Doctors: Print an 5-page detailed information package that provides the following:
|
|
Click here to view feedback from health professionals and users about the results noted from Recovery® with Nutricol®.