Comparative antimutagenic and anticlastogenic effects of green tea and black tea: a review

Tea is the most popular beverage next to water, consumed by over two-thirds of the world's population. It is processed in different ways in different parts of the world to give green, black or oolong tea. Experimental studies have demonstrated the significant antimutagenic and anticlastogenic effects of both green and black tea and its polyphenols in multiple mutational assays. In the present review, we have attempted to evaluate and update the comparative antimutagenic and anticlastogenic effects of green tea, black tea and their polyphenols in different test systems, based on available literature. Existing reports have suggested that the protective effects of black tea is as good as green tea, however, more studies on black tea and its polyphenols are needed before a final conclusion can be made.     

Effect of green tea and black tea on the metabolisms of mineral elements in old rats

A 2-mo experiment with the white Sprague-Dawley (SD) rats was conducted to investigate the effect of the water extracts of black tea (BTWE) and green tea (GTWE) and the black tea leaves (BTF) and the green tea leaves (GTF) on the metabolism of mineral elements. One hundred eight 12-mo-old white SD rats were randomly divided into 13 groups; 6 of these drank the BTWE or GTWE in which the water extracts concentrations of black tea or green tea were, respectively, 0.6%, 1.2%, and 2.4%, and 6 of these had black tea leaves (BTF) and green tea leaves (GTF) added in which the contents of BTF or GTF were, respectively, 0.5%, 1.0%, and 2.0%, one of these was control. The teas and their water extracts could promote the absorption of manganese and copper. In GTF, BTF, GTWE, and BTWE, the apparent absorption rates of manganese were significantly increased. The manganese contents in the tibia were also elevated, and the differences between GTWE and GTF were significant. The apparent absorption rates of copper and the copper contents in the tibia were increased, but not significantly. The teas and their water extracts inhibited the absorption of calcium (p > 0.05) and iron (p < 0.05). The cerebrum calcium contents were significantly decreased, but the contents of calcium and iron in tibia were not significantly changed. Compared with the control, although the apparent absorption rates of aluminum in all experimental groups were not observed to be different, the aluminum contents in the tibia (p > 0.05) and cerebrum (p < 0.05) were increased. GTF and GTWE decreased the apparent absorption rates of zinc, but BTF and BTWE increased them; the zinc contents in tibia were a little improved, whereas its contents in the cerebrum were gradually decreased with the increase of tea leaves dose and tea concentration.     

Enhanced inhibition of prostate cancer xenograft tumor growth by combining quercetin and green tea

The chemopreventive activity of green tea (GT) is limited by the low bioavailability and extensive methylation of GT polyphenols (GTPs) in vivo. We determined whether a methylation inhibitor quercetin (Q) will enhance the chemoprevention of prostate cancer in vivo. Androgen-sensitive LAPC-4 prostate cancer cells were injected subcutaneously into severe combined immunodeficiency (SCID) mice one week before the intervention. The concentration of GTPs in brewed tea administered as drinking water was 0.07% and Q was supplemented in diet at 0.2% or 0.4%. After 6-weeks of intervention tumor growth was inhibited by 3% (0.2% Q), 15% (0.4% Q), 21% (GT), 28% (GT+0.2% Q) and 45% (GT+0.4% Q) compared to control. The concentration of non-methylated GTPs was significantly increased in tumor tissue with GT+0.4% Q treatment compared to GT alone, and was associated with a decreased protein expression of catechol-O-methyltransferase and multidrug resistance-associated protein (MRP)-1. The combination treatment was also associated with a significant increase in the inhibition of proliferation, androgen receptor and phosphatidylinositol 3-kinase/Akt signaling, and stimulation of apoptosis. The combined effect of GT+0.4% Q on tumor inhibition was further confirmed in another experiment where the intervention started prior to tumor inoculation. These results provide a novel regimen by combining GT and Q to improve chemoprevention in a non-toxic manner and warrant future studies in humans.     

Prokinetic effect of black tea on gastrointestinal motility

The gastrokinetic effects of hot water extract of black tea [Camellia sinensis, (L) O. Kuntze (Theaceae)] on gastrointestinal motility were studied both in vivo and in vitro. The extract significantly accelerated the gastrointestinal transit (GIT) in vivo in mice. These facilitatory effect was reduced after pretreatment with atropine, hemicholinium-3, morphine, indomethacin, McN-A-343 and L-arginine. In guinea pig ileum, the extract facilitated the peristaltic reflex in response to pressures in normal preparation. The black tea extract and L-NMMA (nitric oxide synthase inhibitor) significantly reduced the electrical field stimulated nonadrenergic, noncholinergic (NANC) relaxation of isolated rat fundal strips. The extract markedly enhanced the tonic ('hump') responses to transmural stimulation in longitudinal muscle of guinea pig ileum which was unaltered in the presence of atropine. These findings suggest a cholinergic involvement and a partial role of prostaglandin and nitric oxide in the mechanism of action of black tea extract on gastrointestinal motility. To determine the effective constituents in black tea responsible for this activity, the effect of black tea polyphenols on GIT were also studied. Thearubigin fraction (but not theaflavin) accelerated GIT significantly which suggests its involvement in the prokinetic effect of black tea.     

Effects of dietary powdered green tea and theanine on tumor growth and endogenous hyperlipidemia in hepatoma-bearing rats

The effects of dietary powdered green tea (PGT) and theanine on in vivo hepatoma growth and cancerous hyperlipidemia were investigated in rats that had been implanted with a rat ascites hepatoma cell line of AH109A cells. The hepatoma-bearing rats were fed with a 20% casein diet (20C), 20C containing 2% PGT, or 20C containing 0.1% theanine for 14 days. Dietary PGT significantly and time-dependently reduced the solid tumor volume and weight as did dietary theanine. The hepatoma-induced endogenous hyperlipidemia, which was characterized by rises in the serum cholesterol (hypercholesterolemia) and triglyceride (hypertriglyceridemia) levels, was significantly suppressed by PGT and theanine supplementation. Bile acid excretion into the feces was significantly higher in the PGT- and theanine-fed rats than in the control rats. This inhibition of hypercholesterolemia may have resulted from tumor growth suppression as well as increased excretion of steroids from the body. These results suggest that PGT had both anti-proliferative activity toward hepatoma cells and hypolipidemic activity in the hepatoma bearing rats. They also suggest that theanine was, at least in part, responsible for the PGT actions.     

Inhibitory effect of 5-FU loaded ultrasound microbubbles on tumor growth and angiogenesis

The anti-neovascularization treatment is one of the effective strategies for tumor molecular target therapy. At present, the target and effect of the anti-neovascularization treatment is limited, and it is urgent to establish a new vascular targeting strategy to effectively treat tumors. In this work, we used high intensity focused ultrasound (HIFU) combined with targeted microbubbles to establish a molecular targeted ultrasound response microbubble for neovascular cells. Furthermore, the effects of drug loaded microbubbles on neovascularization and tumor cells were studied. The tumor vascular targeted and ultrasound-responsive microbubbles of 5-FU@DLL4-MBs were prepared by the thin-film dispersion method. The size and zeta potential of 5-FU@DLL4-MBs was about 1248 nm and −9.1 mV. 5-FU@DLL4-MBs released 5-FU showed an ultrasound-responsive manner, and had better vascular-targeting ability. Furthermore, the 5-FU@DLL4-MBs showed the strongest cytotoxic effect on HUVECs or HepG-2 cells and can be effectively internalized into the HUVECs cells. Thus, 5-FU@DLL4-MBs combined with HIFU can be considered as a potential method for antitumor angiogenesis in the future.     

Extraction behavior of caffeine and EGCG from green and black tea

A dipping method was developed to extract the catechins (EGCG) and alkaloids (caffeine) from green tea (Korea) and black tea (Sri Lanka). The effects of the solvent composition (water vs. ethanol), extraction time, temperatures, and solvent pH on the amount of catechins (EGCG) and alkaloids (caffeine) extracted from green and black tea were investigated. Reversedphase high-performance liquid chromatography (RP-HPLC) was used to analyze the catechins (EGCG) and alkaloids (caffeine) extracted. The content of EGCG and caffeine in green tea extracts was in the range of 2.04∼0.30 and 10.22∼0.85 mg/g, respectively. The amount of EGCG and caffeine in black tea extracts was in the range of 0.32∼0.24 and 5.26∼1.01 mg/g, respectively. The amount of caffeine extracted from green and black tea was greater than the amount of EGCG. Pure water is the best solvent for extracting EGCG and caffeine from green tea. The amount of caffeine extracted from green and black tea increased as the temperature, extraction time, and hydrogen ion concentration of the solvent increased. Although the amount of EGCG extracted from green tea increased as the temperature increased, the amount of EGCG extracted from black tea was not affected by temperature. The extraction of EGCG from both green and black tea was not affected by the hydrogen ion concentration of the solvent.     

Inhibitory effect of locally produced and exogenous interleukin-6 on tumor growth in vivo

In order to define the potential antitumor activity of the multifunctional cytokine interleukin-6 (IL-6), retrovirus-mediated gene transfer was used to introduce and express a cDNA encoding human IL-6 in the murine fibrosarcoma cell line Fsa-R. Although these genetically modified tumor cells appeared morphologically and phenotypically identical to control Fsa-R cells and had a similar plating efficiency in vitro, they were found to exhibit greatly reduced tumorigenicity in vivo following intravenous injection into syngeneic recipients. Exogenous IL-6 was shown to produce a similar inhibition of tumor growth in the lung if administered intraperitoneally. In contrast, tumor growth in subcutaneous sites was inhibited only if the tumor cells were engineered to express IL-6 locally, or if IL-6 was administered intratumorally. Intraperitoneal injection of IL-6 had no inhibitory effect. Tumors that did grow from IL-6-producing tumor cell inocula in subcutaneous sites were found to contain large numbers of macrophages. These results demonstrate that the antitumor activity of systemically administered IL-6 varies depending on the site of tumor growth and suggest an important role for IL-6 in the recruitment, proliferation and/or survival of tumor-associated macrophages.Supported by grants from the B. C. Health Care Research Foundation (BCHRF), the National Cancer Institute (NCI) and the National Cancer Institute of Canada (NCIC). G.J.D. is a Research Scientist of the National Cancer Institute of Canada (NCIC). R.S.L. is a RSNA Research and Education Fund Scholar     

Inhibitory effect of Chinese green tea on cigarette smoke-induced up-regulation of airway neutrophil elastase and matrix metalloproteinase-12 via antioxidant activity

Our recent study has indicated that Chinese green tea (Lung Chen), in which epigallocatechin-3-gallate (EGCG) accounts for 60% of catechins, protected cigarette smoke-induced lung injury. We now hypothesized that Lung Chen tea may also have potential effect on lung oxidative stress and proteases/anti-proteases in a smoking rat model. Sprague-Dawley rats were exposed to either sham air (SA) or 4% cigarette smoke (CS) plus 2% Lung Chen tea or water by oral gavage. Serine proteases, matrix metalloproteinases (MMPs) and their respective endogenous inhibitors were determined in bronchoalveolar lavage (BAL) and lung tissues by gelatin/casein zymography and biochemical assays. Green tea consumption significantly decreased CS-induced elevation of lung lipid peroxidation marker, malondialdehyde (MDA), and CS-induced up-regulation of neutrophil elastase (NE) concentration and activity along with that of α(1)-antitrypsin (α(1)-AT) and secretory leukoproteinase inhibitor (SLPI) in BAL and lung. In parallel, significant elevation of MMP-12 activity was found in BAL and lung of the CS-exposed group, which returned to the levels of SA-exposed group after green tea consumption but not CS-induced reduction of tissue inhibitor of metalloproteinase (TIMP)-1 activity, which was not reversed by green tea consumption. Taken together, our data supported the presence of local oxidative stress and protease/anti-protease imbalance in the airways after CS exposure, which might be alleviated by green tea consumption through its biological antioxidant activity.     

Inhibitory effect of Chinese green tea on cigarette smoke-induced up-regulation of airway neutrophil elastase and matrix metalloproteinase-12 via antioxidant activity

Abstract

Our recent study has indicated that Chinese green tea (Lung Chen), in which epigallocatechin-3-gallate (EGCG) accounts for 60% of catechins, protected cigarette smoke-induced lung injury. We now hypothesized that Lung Chen tea may also have potential effect on lung oxidative stress and proteases/anti-proteases in a smoking rat model. Sprague–Dawley rats were exposed to either sham air (SA) or 4% cigarette smoke (CS) plus 2% Lung Chen tea or water by oral gavage. Serine proteases, matrix metalloproteinases (MMPs) and their respective endogenous inhibitors were determined in bronchoalveolar lavage (BAL) and lung tissues by gelatin/casein zymography and biochemical assays. Green tea consumption significantly decreased CS-induced elevation of lung lipid peroxidation marker, malondialdehyde (MDA), and CS-induced up-regulation of neutrophil elastase (NE) concentration and activity along with that of α₁-antitrypsin (α₁-AT) and secretory leukoproteinase inhibitor (SLPI) in BAL and lung. In parallel, significant elevation of MMP-12 activity was found in BAL and lung of the CS-exposed group, which returned to the levels of SA-exposed group after green tea consumption but not CS-induced reduction of tissue inhibitor of metalloproteinase (TIMP)-1 activity, which was not reversed by green tea consumption. Taken together, our data supported the presence of local oxidative stress and protease/anti-protease imbalance in the airways after CS exposure, which might be alleviated by green tea consumption through its biological antioxidant activity.     

Antimutagenic activity of green tea and black tea extracts studied in a dynamic in vitro gastrointestinal model

An in vitro gastrointestinal model, which simulates the conditions in the human digestive tract, was used to determine potential antimutagenic activity of extracts of black tea and green tea. In this paper, results are presented on the availability for absorption of potential antimutagenic compounds present in tea and on the influence of the food matrix on this activity. Between 60 and 180min after the tea was introduced into the model, antimutagenic activity was recovered from the jejunal compartment by means of dialysis: the dialysate appeared to inhibit the mutagenicity of the food mutagen MeIQx in the direct plate assay with Salmonella typhimurium (Ames test). The maximum inhibition was measured at 2h after the start of the experiment and was comparable for black tea and green tea extract. To determine the influence of food matrices on the antimutagenic activity of tea, the model was loaded with black tea together with milk or a homogenized standard breakfast. The maximum inhibition observed with black tea was reduced by 22, 42 and 78% in the presence of whole milk, semi-skimmed milk, and skimmed milk, respectively. Whole milk and skimmed milk abolished the antimutagenic activity of green tea by more than 90%; for semi-skimmed milk the inhibition was more than 60%. When a homogenized breakfast was added into the model together with the black tea extract, the antimutagenic activity was completely eliminated. When tea and MeIQx were added together into the digestion model, MeIQx mutagenicity was efficiently inhibited, with green tea showing a slightly stronger antimutagenic activity than black tea. In this case, the addition of milk had only a small inhibiting effect on the antimutagenicity.Antioxidant capacity and the concentration of catechins were also measured in the jejunal dialysates. The reduction in antimutagenic activity corresponded with reduction in antioxidant capacity and with a decrease of concentration of three catechins, viz. catechin, epigallocatechin gallate and epigallocatechin. The in vitro gastrointestinal model appears to be a useful tool to study the antimutagenicity of food components.     

Potent suppressive effect of green tea polyphenols on tobacco-induced mutagenicity

Antimutagenic activity of green tea (Camellia sinensis) was studied using Salmonella typhimurium strains (TA 102) (Ames test). Aqueous tobacco extract was found to be mutagenic to S. typhimurium TA 102 at concentration of 50 mg/plate. Green tea polyphenols was found to inhibit the mutagenicity of tobacco in a concentration-dependent manner. Concentrations needed for 50% inhibition of mutagen-induced revertant formation was found to be 5 mg/plate. Green tea polyphenols was also found to inhibit the urinary mutagenicity in rats induced by tobacco extract. Moreover green tea polyphenols were found to inhibit in vitro nitrosation reaction produced by reaction sodium nitrite and methyl urea and further inhibition of mutagenicity indicating that green tea has dual action to bring out a reduction in the mutagenic and carcinogenic potential of tobacco.     

Polyphenols in brewed green tea inhibit prostate tumor xenograft growth by localizing to the tumor and decreasing oxidative stress and angiogenesis

It has been demonstrated in various animal models that the oral administration of green tea (GT) extracts in drinking water can inhibit tumor growth, but the effects of brewed GT on factors promoting tumor growth, including oxidant damage of DNA and protein, angiogenesis and DNA methylation, have not been tested in an animal model. To explore these potential mechanisms, brewed GT was administered instead of drinking water to male severe combined immunodeficiency (SCID) mice with androgen-dependent human LAPC4 prostate cancer cell subcutaneous xenografts. Tumor volume was decreased significantly in mice consuming GT, and tumor size was significantly correlated with GT polyphenol (GTP) content in tumor tissue. There was a significant reduction in hypoxia-inducible factor 1-alpha and vascular endothelial growth factor protein expression. GT consumption significantly reduced oxidative DNA and protein damage in tumor tissue as determined by 8-hydroxydeoxyguanosine/deoxyguanosine ratio and protein carbonyl assay, respectively. Methylation is known to inhibit antioxidative enzymes such as glutathione S-transferase pi to permit reactive oxygen species promotion of tumor growth. GT inhibited tumor 5-cytosine DNA methyltransferase 1 mRNA and protein expression significantly, which may contribute to the inhibition of tumor growth by reactivation of antioxidative enzymes. This study advances our understanding of tumor growth inhibition by brewed GT in an animal model by demonstrating tissue localization of GTPs in correlation with inhibition of tumor growth. Our results suggest that the inhibition of tumor growth is due to GTP-mediated inhibition of oxidative stress and angiogenesis in the LAPC4 xenograft prostate tumor in SCID mice.     

Antiviral activity of green tea and black tea polyphenols in prophylaxis and treatment of COVID-19: A review

BackgroundThe rapid spread of novel coronavirus called SARS-CoV-2 or nCoV has caused countries all over the world to impose lockdowns and undertake stringent preventive measures. This new positive-sense single-stranded RNA strain of coronavirus spreads through droplets of saliva and nasal discharge.PurposeUS FDA has authorized the emergency use of Remdesivir looking at the increasing number of cases of COVID-19, however there is still no drug approved to treat COVID-19. An alternative way of treatment could be the use of naturally derived molecules with known antiviral properties.MethodWe reviewed the antiviral activities of two polyphenols derived from tea, epigallocatechin-3-gallate (EGCG) from green tea and theaflavins from black tea. Both green tea and black tea polyphenols have been reported to exhibit antiviral activities against various viruses, especially positive-sense single-stranded RNA viruses.ResultsRecent studies have revealed the possible binding sites present on SARS-CoV-2 and studied their interactions with tea polyphenols. EGCG and theaflavins, especially theaflavin-3,3′-digallate (TF3) have shown a significant interaction with the receptors under consideration in this review. Some docking studies further emphasize on the activity of these polyphenols against COVID-19.ConclusionThis review summarizes the available reports and evidences which support the use of tea polyphenols as potential candidates in prophylaxis and treatment of COVID-19.