BMC Pulmonary Medicine volume 23Article number: Thermogenesis and muscle growth this article. Metrics details. Numerous studies have reported the association Green tea extract for respiratory health tea Non-toxic personal care products and lung diseases.
However, the probable relationship between gespiratory consumption on respiratoory diseases heqlth Green tea extract for respiratory health controversial and it is unclear whether these findings are due to reverse causality or confounding factor.
In order to systematically investigate the causal connection respiratoory tea intake on respiratory system disorders, we employed a two-sample Time-restricted eating window randomized MR study.
Genetic instruments reespiratory tea intake were identified from a genome-wide association study GWAS involvingindividuals. Data on lung Grsen were collected from a variety of publicly available genome-wide association studies.
The main method used for MR Green tea extract for respiratory health is extgact inverse variance weighting Eztract method. To ensure the accuracy fog the findings, further sensitivity analysis te conducted. The reliability of the results was further demonstrated by four additional MR analysis techniques and respirratory sensitivity testing.
We rrespiratory no evidence of a link between tea intake on lung diseases ta our MR results based on genetic information. Peer Hormone-Free Milk reports. Fxtract diseases pose a serious threat to our society in terms of both the economy and public health.
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Therefore, ongoing and effective prevention measures and strategies rwspiratory key factors in managing rea disease. Numerous studies have reapiratory drinking tea have many health benefits, such as a decreased risk of diabetes [ 910 ], Menstrual health support groups disease [ 1112 respirator, and several tumor diseases [ 13 wxtract, 14 Appetite control coach. However, the association between drinking tea and respiratory diseases remain controversial.
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It remains unclear whether the observed heapth between tea consumption teaa the risk of lung diseases is causal. Mendelian randomization MR is a novel method for explaining respiiratory bias [ 21 ]. Energizing workouts method integrates pooled data from genome-wide association studies GWAS and uses extradt nucleotide polymorphisms Green tea extract for respiratory health as Liver detoxification diet variables heaoth infer causal relationships between exposure and outcome [ 22 ].
Because of the Fat-burning exercises for seniors assignment of genetic variants during meiosis, respiratroy is fog to simulate natural randomized controlled trials, thus minimizing the interference of confounding factors and reverse causality in traditional epidemiology, and avoiding the difficulties and ethical issues associated with heealth implementation hwalth randomized Green tea extract for respiratory health trials [ 2324 ].
In order to investigate the causal link between tea consumption and lung diseases, respiratogy performed an MR analysis. We conducted a two-sample Mendelian Gteen analysis to investigate the causal association between tea intake and Cholesterol level guidelines diseases, using summary statistics from GWAS datasets.
The exposure and outcome variables in our analysis were derived from separate GWAS datasets. We performed sensitivity analyses using different MR methods with varying model assumptions. Our study was based on three fundamental assumptions: first, a strong correlation must exist between the instrumental variable and the exposure factor; second, the instrumental variable must not be associated with any potential confounders; and third, the instrumental variable can only affect the outcome through the exposure variable [ 25 ].
The present concept of MR research is schematically displayed in Fig. The instrumental variable in this Mendelian randomization study was based on the hypothesis that it was related to tea intake but not to confounding variables, and that it only impacted the risk of six lung diseases through tea intake.
A large GWAS involvingsamples of European ancestry was conducted by the MRC-IEU consortium, and the results discovered SNPs linked to tea consumption.
This genome-wide association study GWAS was adjusted for various factors, including sex, genotyping arrays, and other variables. According to the survey results, the mean value of tea intake was 3. Data on six lung diseases were collected from multiple sources, including the MRC-IEU, the Neale Lab, and the FinnGen consortium.
For these exposures, detailed information on the data sources for instrumental variables can be found in Supplementary Table 1. Of particular significance, all of the individuals are of European ancestry. We applied several measures to assure the quality of valid instrumental SNPs for our analysis Fig.
Third, we utilized the F-statistic to quantify the intensity of genetic variation and excluded SNPs with an F-statistic less than 10, which indicated that the genetic variation in these SNPs was relatively weak and did not meet the criteria for our study [ 26 ].
Fourth, we excluded SNPs with minor allele frequencies MAF below 0. Fifth, To ensure that the effect of SNPs on exposure is attributed to the same allele as the effect on the outcome, palindromic SNPs with intermediate allele frequencies were excluded from the analysis [ 27 ].
If a significant association was found, those instrumental factors were removed from further analysis. Seventh, using Phenoscanner, a website that offers comprehensive data on the relationship between genotype and phenotype, to perform checks and then remove SNPs associated with confounding factors.
Overall, the aforementioned initial three steps satisfy the assumption of relevance, while steps 3—6 fulfill the exclusion restriction assumption and indicate the characteristics of the selected instrumental variables in the outcome. The independence assumption is upheld by using Phenoscanner to detect SNPs connected to confounding variables.
The step of examining SNPs related to confounding factors using Phenoscanner satisfies the independence assumption. After applying the aforementioned criteria, a final set of SNPs suitable for further analysis was obtained.
The key analysis in this MR study was conducted using the inverse variance weighted IVW method [ 28 ]. The approach employs a weighted regression involving multiple genetic variants to assess causal effects.
Moreover, MR-Egger, weighted median, simple mode, and weighted mode were employed as supplementary methods to IVW [ 30 ].
Similar to IVW, the MR Egger method is a weighted regression of SNP results from SNP exposure associations, but unlike the IVW method, the intercept is not constrained to zero. The slope of the MR-Egger method gives an unbiased estimate even if all instruments are invalidated [ 3132 ].
The weighted mode method estimates the causal effect by clustering SNPs into subsets and focusing on the subset with the highest number of SNPs [ 3536 ]. The simple mode offers robustness against pleiotropy, although it lacks as much power as IVW [ 37 ].
While IVW can provide the most accurate results when all instrumental variables used are valid SNPs, the other four methods have their own advantages and applicability in different situations.
Therefore, if the results of the five methods are consistent, it can enhance the robustness of the findings. To verify the validity of our conclusions, we conducted several tests to evaluate heterogeneity and horizontal pleiotropy.
We then examined horizontal pleiotropy using both MR pleiotropy residual sum and outlier MR-PRESSO analysis and MR-Egger intercept [ 3940 ].
MR-PRESSO was not only used to examine horizontal pleiotropy but was also utilized to detect and correct potential outliers in the instrumental variable analysis. We assessed the outcome to be untrustworthy if the p -value of the MR-Egger intercept was less than 0.
To determine if a single SNP influences the causal link between tea consumption and lung illness, leave-one-out analysis was used [ 41 ]. All data analyses were conducted in R version 4. We screened SNPs associated with tea intake and obtained a total of 41 SNPs all SNPs had p values less than 5E and r 2 values under 0.
The F -statistics of these SNPs were all greater than the conventional threshold of 10, indicating that the instrument bias was weak in our MR study and could not significantly affect the estimation of causal effects Supplementary Table 2.
During the screening process, we removed SNPs associated with lung diseases and its related confounders rs, rs, rs, rsand Palindromic structure SNPs rs, rs, rs, rs, rs, rs, rs, rsand SNPs that were not available in the outcome dataset. We give comprehensive information about all relevant SNPs, as shown in Supplementary Tables 3 — 8.
The results of the IVW analysis revealed that a genetically predicted change in tea intake per unit SD SD: 2. Similar outcomes were basically achieved by the complementary four methods: MR-Egger, weighted median, weighted mode, and simple mode.
An outlier SNP rs was found in the MR-PRESSO test when the outcome variable was COPD. In order to avoid the bias caused by it, we removed it and performed MR analysis again. Forest plot showed the causal association between tea intake and lung disease. A IPF; B lung cancer; C COPD; D acute bronchitis; E tuberculosis; F pneumonia.
We conducted separate leave-one-out analyses for each outcome. The results consistently showed that none of the SNPs were significantly correlated with the non-causal relationship between tea intake and lung diseases Fig.
MR leave-one-out sensitivity analysis of tea intake on lung disease. Circles indicate the results of MR analysis of remaining SNPs on tea intake on lung disease after omitting each SNP in turn. Bars indicate CI.
Estimating heterogeneity using funnel plots of individual causal relationships between tea intake and lung disease. In this study, the Mendelian randomization analyses were performed using a large sample GWAS database to determine the association between tea consumption and six common lung diseases.
Our MR research found no evidence of a link between drinking tea and any of the six prevalent lung disease: IPF, lung cancer, COPD, tuberculosis, pneumonia, and acute bronchitis.
In the last decade, many epidemiologic studies have examined the relationship between tea consumption and respiratory diseases. However, to this day it has not been possible to draw definitive conclusions. For example, a study by Vu Thanh-Huyen T et al. showed a favorable correlation between tea and the incidence of pneumonia [ 42 ].
A large cohort study involving 19, men and 21, women showed that tea consumption was linked to a decreased risk of death from pneumonia in Japanese women [ 43 ].
However, a hospital-based case-control study found no association between pneumonia and tea drinking [ 44 ], which is in accord with our findings.
Similarly, human studies have shown that green tea catechins does not affect the activity of the CYPIA2, CYP2D6, CYP2C9 and CYP3A4 enzymes, but in vitro studies have shown that green tea extract binds bortezomib and lessens its activity [ 45 ].
In this Mendelian randomization study, we did not observe a protective effect of tea consumption against several common lung diseases, which contradicted the results of some previous observational studies.
In comparing our findings with those of previous studies, it is important to note that there are several potential reasons for this discrepancy. First, observational studies cannot be completely devoid of residual confounding and reverse causality.
For instance, experiments in rats have shown that EGCG, a major component of green tea, may alleviate lung injury by inhibiting oxidative stress [ 46 ].
In addition to its antioxidant effects, the presence of several substances in tea, such as polyphenols, flavonoids, theanine, and EGCG, which have immunomodulatory, anti-inflammatory, is all related to the risk of respiratory diseases [ 4748 ].
: Green tea extract for respiratory health| Green tea daily wards off influenza and other respiratory viruses, say researchers | People with anemia, diabetes, glaucoma, or osteoporosis should ask their health care provider before drinking green tea or taking an extract. People who drink large amounts of caffeine, including caffeine from green tea, for long periods of time may experience irritability, insomnia, heart palpitations, and dizziness. Caffeine overdose can cause nausea, vomiting, diarrhea, headaches, and loss of appetite. If you are drinking a lot of tea and start to vomit or have abdominal spasms, you may have caffeine poisoning. If your symptoms are severe, lower your caffeine intake and see your health care provider. If you are being treated with any of the following medications, you should not drink green tea or take green tea extract without first talking to your health care provider:. Green tea may inhibit the actions of adenosine, a medication given in the hospital for an irregular and usually unstable heart rhythm. Green tea may increase the effectiveness of beta-lactam antibiotics by making bacteria less resistant to treatment. Caffeine, including caffeine from green tea, may reduce the sedative effects of these medications commonly used to treat anxiety, such as diazepam Valium and lorazepam Ativan. Beta-blockers, Propranolol, and Metoprolol. Caffeine, including caffeine from green tea, may increase blood pressure in people taking propranolol Inderal and metoprolol Lopressor, Toprol XL. These medications are used to treat high blood pressure and heart disease. Blood-Thinning Medications. People who take warfarin Coudamin should not drink green tea. Since green tea contains vitamin K, it can make this medication ineffective. Other compounds in green tea may slow blood clotting and therefore increase the blood-thinning effect of these medications. You should not mix green tea and aspirin because they both prevent blood from clotting. Using the two together may increase your risk of bleeding. If you are taking medications that promote blood thinning, discuss green tea consumption with your physician. The combination of green tea and chemotherapy medications, specifically doxorubicin and tamoxifen, increased the effectiveness of these medications in laboratory tests. However, the same results have not been found in studies on people. On the other hand, there have been reports of both green and black tea extracts affecting a gene in prostate cancer cells that may make them less sensitive to chemotherapy drugs. For that reason, people should talk to their doctors before drinking black and green tea or taking tea extracts while undergoing chemotherapy. Clozapine Clozaril. The effects of the clozapine may be reduced if taken within 40 minutes after drinking green tea. When taken with ephedrine, green tea may cause agitation, tremors, insomnia, and weight loss. Green tea has been shown to reduce blood levels of lithium, a medication used to treat bipolar disorder. That can make lithium less effective. Monoamine Oxidase Inhibitors MAOIs. Green tea may cause a severe increase in blood pressure, called a "hypertensive crisis," when taken together with these drugs used to treat depression. Examples of MAOIs include:. Birth control pills. Oral contraceptives can prolong the amount of time caffeine stays in the body, which may increase its stimulating effects. A combination of caffeine, including caffeine from green tea, and phenylpropanolamine, used in many over-the-counter and prescription cough and cold medications and weight loss products, may cause mania and a severe increase in blood pressure. The FDA issued a public health advisory in November to warn people of the risk of bleeding in the brain from use of this medication and urged all manufacturers of this drug to remove it from the market. Most drugs that contained phenylpropanolamine have been reformulated without it. Quinolone antibiotics. Green tea may make these medications more effective and also increase the risk of side effects. These medications include:. Other medications. Green tea, especially caffeinated green tea, may interact with a number for medications, including:. To be safe, check with your health care provider before drinking or taking green tea if you also take other medications. Baladia E, Basulto J, Manera M, Martinez R, Calbet D. Effect of green tea or green tea extract consumption on body weight and body composition: systematic review and meta-analysis. Nutr Hosp. Belza A, Toubro S, Astrup A. The effect of caffeine, green tea and tyrosine on thermogenesis and energy intake. Eur J Clin Nutr. 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Does supplementation with green tea extract improve insulin resistance in obese type 2 diabetics? A randomized, double-blind, and placebo-controlled clinical trial. Altern Med Rev. Inoue M, Tajima K, Mizutani M, et al. Regular consumption of green tea and the risk of breast cancer recurrence: follow-up study from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center HERPACC , Japan. Cancer Lett. Jian L, Xie LP, Lee AH, Binns CW. Protective effect of green tea against prostate cancer: a case-control study in southeast China. Int J Cancer Jan 1, ; 1 Jiao H, Hu G, Gu D, Ni X. Having a promising efficacy on type II diabetes, it's definitely a green tea time. Curr Med Chem. Jin X, Zheng RH, Li YM. Green tea consumption and liver disease: a systematic review. Liver Int. Kato A, Minoshima Y, Yamamoto J, Adachi I, Watson AA, Nash RJ. Protective effects of dietary chamomile tea on diabetic complications. J Agric Food Chem. Khalesi S, Sun J, Buys N, et al. Green tea catechins and blood pressure: a systematic review and meta-analysis of randomised controlled trials. Eur J Nutr. Kimura K, Ozeki M, Juneja LR, Ohira H. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. Koo SI, Noh SK. Green tea as inhibitor of the intestinal absorption of lipids: potential mechanism for its lipid-lowering effect. J Nutr Biochem. Kovacs EM, Lejeune MP, Nijs I, Westerterp-Plantenga MS. Effects of green tea on weight maintenance after body-weight loss. Mar 1, ;91 3 Kuriyama S, Shimazu T, Ohmori K, Kikuchi N, Nakaya N, Nishino Y, Tsubono Y, Tsuji I. Green tea consumption and mortality due to cardiovascular disease, cancer and all causes in Japan: the Ohsaki study. Lee W, Min WK, Chun S, Lee YW, Park H, Lee do H, Lee YK, Son JE. Long-term effects of green tea ingestion on atherosclerotic biological markers in smokers. Clin Biochem. Jan 1, ;38 1 Liu K, Zhou R, Wang B, et al. Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials. Am J Clin Nutr. Low Dog T, Riley D, Carter T. Traditional and alternative therapies for breast cancer. Alt Ther. Miura Y, Chiba T, Tomita I, et al. Tea catechins prevent the development of atherosclerosis in apoprotein E-deficient mice. J Nutr. Nagao T, Hase T, Tokimitsu I. A green tea extract high in catechins reduces body fat and cardiovascular risks in humans. Obesity Silver Spring. Narotzki B, Reznick AZ, Aizenbud D, Levy Y. Green tea: a promising natural product in oral health. Arch Oral Biol. Noguchi-Shinohara M, Yuki S, Dohmoto C, et al. Consumption of green tea, but not black tea or coffee, is associated with reduced risk of cognitive decline. PLoS One. Peters U, Poole C, Arab L. Does tea affect cardiovascular disease? A meta-analysis. Am J Epidemiol. Pianetti S, Guo S, Kavanagh KT, Sonenshein GE. Rowe CA, Nantz MP, Bukowski JF, Percival SS. Specific formulation of Camellia sinensis prevents cold and flu symptoms and enhances gammadelta T cell function: a randomized, double-blind, placebo-controlled study. Ryu OH, Lee J, Lee KW, et al. Effects of green tea consumption on inflammation, insulin resistance and pulse wave velocity in type 2 diabetes patients. Diabetes Res Clin Pract. Sasazuki S, Kodama H, Yoshimasu K et al. Relation between green tea consumption and the severity of coronary atherosclerosis among Japanese men and women. Ann Epidemiol. Setiawan VW, Zhang ZF, Yu GP, et al. Protective effect of green tea on the risks of chronic gastritis and stomach cancer. Int J Cancer. Shankar S, Ganapathy S, Hingorani SR, Srivastava RK. EGCG inhibits growth, invasion, angiogenesis and metastasis of pancreatic cancer. Front Biosci. Steptoe A, Gibson EL, Vuonovirta R, Hamer M, Wardle J, Rycroft JA, Martin JF, Erusalimsky JD. The effects of chronic tea intake on platelet activation and inflammation: a double-blind placebo controlled trial. Suzuki Y, Tsubono Y, Nakaya N, Suzuki Y, Koizumi Y, Tsuji I. Green tea and the risk of breast cancer: pooled analysis of two prospective studies in Japan. Br J Cancer. Apr 5, ;90 7 Thatte U, Bagadey S, Dahanukar S. Modulation of programmed cell death by medicinal plants. Cell Mol Biol. Thavanesan N. The putative effects of green tea on body fat: an evaluation of the evidence and a review of the potential mechanisms. Trudel D, Labbe DP, Bairati I, Fradet V, Bazinet L, Tetu B. Green tea for ovarian cancer prevention and treatment: a systemic review of the in vitro, in vivo and epidemiological studies. Gynecol Oncol. Tsubono Y, Nishino Y, Komatsu S, et al. Green tea and the risk of gastric cancer in Japan. N Engl J Med. Vinson JA, Teufel K, Wu N. Green and black teas inhibit atherosclerosis by lipid, antioxidant, and fibrinolytic mechanisms. Wargovich MJ, Woods C, Hollis DM, Zander ME. Herbals, cancer prevention and health. Westerterp-Plantenga MS, Lejeune MP, Kovacs EM. Body weight and weight maintenance in relation to habitual caffeine intake and green tea. Obes Res. Jul ;13 7 Wu AH, Butler LM. Equal amounts of protein were separated by SDS-PAGE, transferred to a PVDF membrane Millipore Corp. The membranes were then incubated with the following primary antibodies at room temperature for 3 h: Nrf-2 ; Sigma , HO-1 , NQO-1 both from Millipore or β-actin ,; Cell Signaling Technology, Inc. After washing with TBS-T, the membranes were incubated with HRP-conjugated secondary antibodies. The protein bands were visualized using enhanced chemiluminescence with a Super Signal detection kit Boster Biological Technology. Ten fields per section at × magnification were randomly selected per rat, and two blinded pathologists carefully and independently examined 60 fields per group using an Olympus microscope Olympus, Tokyo, Japan. The total score of each section was calculated, and the mean score of each group was determined as the total score of all sections divided by six. Lung sections stained with Sirius red were observed and images were captured using a polarizing microscope. For the immunohistochemical analyses of SPB and α-SMA, staining density was determined using Image Proplus software in one field with a prominent DAB reaction for each section under × magnification for a total of six fields per group. Large airways and lung vessels were excluded from all analyses. Data were expressed as the means ± standard deviations SDs. Irradiated rats treated with EGCG All control animals survived to 4 months without death. Congested edema and bleeding sites were significantly attenuated in DEX-treated pulmonary tissues compared with radiation-only animals at 15 and 30 days post-irradiation. Pulmonary collapse and gray fibrous nodules were similar in DEX-treated and radiation-only animals at 60 and days post-irradiation. Bleeding sites were seldom observed in EGCG-treated pulmonary tissues at 15 days post-irradiation. Signs of congested edema were also significantly attenuated in EGCG-treated pulmonary tissues compared with DEX-treated and radiation-only tissues at 15, 30 and 60 days post-irradiation. At days post-irradiation, the lungs of EGCG-treated rats showed signs of edema and uneven surfaces as well as scattered punctuate bleeding points. However, neither pulmonary collapse nor gray fibrous nodules were found in EGCG-treated animals at days post-irradiation Fig. These results suggested that EGCG significantly ameliorates irradiation-induced pulmonary fibrosis. Effect of epigallocatechingallate EGCG on the lung appearance at days post gamma-ray irradiation. Untreated irradiated and DEX-treated irradiated animals show marked lung collapse, rough surfaces and gray fibrous nodule development. EGCG treatment animals show lung tissue edema, rough surfaces, scattered punctate bleeding, but no lung collapse and gray fibrous nodules. Bar, 0. We examined whether EGCG treatment influenced the lung index, which refers to the ratio of lung wet weight to body weight. This result matches the morphometric observations of lung appearance in EGCG-treated animals at days post-irradiation Fig. At this time point, edema was still detectable in EGCG-treated animals but was not detected in DEX-treated and untreated irradiated animals. These results indicated that EGCG significantly attenuated congested edema in pulmonary tissues post-irradiation. A The effect of epigallocatechingallate EGCG on the lung index score, B combined alveolitis score, C combined fibrosis score, and D hydroxyproline Hyp content at 15, 30, 60 and days post-irradiation. The bars in the graph are the standard deviations SDs. We examined whether EGCG treatment improves the histological changes that occur in pulmonary tissues post-irradiation. Treatment with EGCG, but not DEX, significantly improved irradiation-induced pathological changes Fig. Effect of epigallocatechingallate EGCG on the histological changes in lung tissue at days post-irradiation. Note that inflammatory cell infiltration, fibrotic lesions and collagen fiber deposition were significantly improved in EGCG-treated animals. Bar, μm. We also examined the degree to which EGCG treatment eliminated Hyp, the major constituent of collagen, from pulmonary tissues. Together, these results showed marked anti-fibrotic effects of EGCG in vivo Fig. We investigated whether EGCG treatment regulates the redox balance post-irradiation. Serum MDA content and SOD activity were measured to assess the oxidative and antioxidant statuses, respectively. The MDA concentration in DEX-treated animals was similar to that of the radiation-only animals at 15, 30, 60 and days post-irradiation Fig. A The effect of epigallocatechingallate EGCG on serum malondialdehyde MDA concentrations, B superoxide dismutase SOD activity, C α smooth muscle actin α-SMA levels and D surfactant protein-B SPB levels at 15, 30, 60 and days post-irradiation. Conversely, the MDA concentrations of the DEX-treated and untreated animals were comparable at 15, 30, 60 and days post-irradiation. These results demonstrated that EGCG treatment modulates redox balance in vivo. The activation and proliferation of myo fibroblasts are important contributors to pulmonary fibrosis. Injury to the AE2 cells directly and indirectly contributes to the effects of irradiation-induced pulmonary injury. Therefore, we investigated the effects of EGCG on myo fibroblasts and AE2 cells. The expression of α-SMA, a myo fibroblast marker, and SPB, an AE2 marker, was investigated using immunohistochemistry on the lung sections. Strong α-SMA expression was observed in the irradiated pulmonary tissues at days post-irradiation. Treatment with EGCG, but not DEX, significantly reduced α-SMA expression Fig. Conversely, weak SPB expression was observed in the irradiated pulmonary tissues at days post-irradiation. Treatment with EGCG, but not DEX, significantly enhanced SPB expression Fig. Effect of epigallocatechingallate EGCG on the α smooth muscle actin α-SMA and surfactant protein-B SPB immunohistochemistry at days post-irradiation. Photomicrographs show the immunohistochemical IHC staining with antibodies detecting α-SMA left column or SPB right column in lung tissue from rats in the non-irradiated normal , irradiated but untreated Radiation , dexamethasone DEX -treated, and EGCG-treated EGCG groups. Myofibroblast accumulation hyperplasia as stained by α-SMA IHC was significantly reduced, and alveolar type II cells stained by SPB IHC were significantly increased in EGCG-treated animals. A morphometric analysis of α-SMA and SPB immunohistochemistry as described in Materials and methods was performed. These results confirmed that EGCG inhibits myo fibroblast proliferation and protects AE2 cells from injury post-irradiation. We examined whether treatment with EGCG reverses the abnormal expression of cytokines in serum following irradiation. A The effect of epigallocatechingallate EGCG on the serum levels of transforming growth factor β1 TGF-β1 , B interleukin IL -6, C IL, and D tumor necrosis factor α TNF-α at 15, 30, 60 and days post-irradiation. The serum TGF-β1 levels in the DEX-treated animals were similar to those of the untreated animals at 30, 60 and days post-irradiation. The serum levels of IL-6, IL, and TNF-α in the DEX-treated animals were similar to those in the radiation-only animals at 60 and days post-irradiation. The bars in each graph are the standard deviations SDs. The levels of IL-6, IL and TNF-α in the DEX-treated animals were similar to those of the radiation-only animals at 60 and days post-irradiation Fig. We also examined whether EGCG treatment activates Nrf-2 signaling and its associated antioxidant enzymes. The protein levels of Nrf-2, HO-1 and NQO-1 were assessed by western blot analysis. This analysis revealed that EGCG administration strongly activated Nrf-2, HO-1, and NQO-1 protein levels, whereas DEX administration weakly activated Nrf-2 levels at 15 days post irradiation Fig. A Epigallocatechingallate EGCG activates nuclear transcription factor NF-E2-related factor 2 Nrf-2 , B heme oxygenase-1 HO-1 and C NAD P H:quinone oxidoreductase-1 NQO-1 protein expression as detected by western blot analysis of lung tissue extracts at 15 days post-irradiation. Immunoblot analysis revealed that the protein expression of Nrf-2, HO-1, and NQO-1 was strongly activated by EGCG administration, while Nrf-2 was weakly activated by dexamethasone DEX. A The protein levels of nuclear transcription factor NF-E2-related factor 2 Nrf-2 , B heme oxygenase-1 HO-1 and C NAD P H:quinone oxidoreductase-1 enzyme NQO-1 were compared using western blot analysis of lung tissue extracts at 15, 30, 60 and 20 days post-irradiation. Data are presented as the means ± standard deviations SDs. Results of the present study have shown that irradiation-induced pulmonary fibrosis in rats is principally ameliorated by EGCG administration. EGCG treatment reduced the mortality rate and lung index score, alleviated lung histological damage, reduced collagen deposition, modulated the redox state of serum, inhibited myo fibroblast proliferation, protected AE2 cells, and regulated the serum levels of TGF-β1, IL-6, IL, and TNF-α. We also showed that EGCG treatment activated Nrf-2 and its downstream antioxidant enzymes HO-1 and NQO The DEX treatment of irradiation-induced pulmonary fibrosis did not produce similarly ameliorative effects. Given these results, we demonstrated that EGCG treatment significantly ameliorates irradiation-induced pulmonary fibrosis. Our data reveal that EGCG has potential for treatments of irradiation-induced pulmonary fibrosis. Increasing evidence indicates that oxidative stress and ROS contribute directly and indirectly to the formation of irradiation-induced pulmonary fibrosis The ROS-induced activation of inflammatory cells including macrophages, monocytes, and neutrophils can cause a positive feedback loop in which an increased expression of a variety of intracellular oxidative enzymes and large amounts of ROS and reactive nitrogen species RNS are synthesized and released to remove necrotic tissue 20 , Therefore, any therapeutic intervention that defends against or alleviates oxidant insults may be used to treat irradiation-induced pulmonary fibrosis. Due to its potent antioxidant activity, a variety of animal models have shown that the tea polyphenol EGCG is an effective scavenger of ROS and free radicals with regard to tumors, cardiovascular diseases, and neurological diseases both in vitro and in vivo The antioxidant activity of EGCG which likely involves the quenching of ROS, the interception of free radicals, or both is most likely mediated by an H-atom transfer HAT reaction in which intramolecular hydrogen bonding stabilizes the resultant phenoxy radical Previous studies have suggested that EGCG administration inhibits lipopolysaccharide 8 and bleomycin-induced pulmonary fibrosis 11 — Thus, we hypothesized that scavenging free radicals with EGCG, a natural antioxidant extracted from green tea, inhibits irradiation-induced pulmonary fibrosis. MDA levels most likely reflect the degree of organic lipid peroxidation, which denotes the severity of damage to cell membranes This enzyme can neutralize free radical forms of oxygen, thereby protecting cells from oxidative damage. Moreover, injections of SOD 24 and the SOD mimetic AEOL 25 have shown protective effects in animal models of radiation-induced fibrosis. Our investigation showed that the serum levels of MDA and inflammatory cytokines decreased, and serum SOD activity increased in DEX-treated animals compared with radiation-only animals at 15 and 30 days post-irradiation. However, these therapeutic benefits ceased with treatment. EGCG-treated rats had greater SOD activity than any other group of rats, including the non-irradiated normal controls, at all time points 15— days post-irradiation. This result suggests that EGCG reduced oxidative stress, at least in part, by increasing the systemic production of antioxidant proteins. TGF-β1 is a powerful cytokine that can promote fibroblast proliferation and maturation, thereby accelerating the development of pulmonary fibrosis Wang et al demonstrated that TGF-β1 levels were positively correlated with the incidence of radiation-treatment-induced lung injury among patients with lung cancer TNF-α is a driving factor within pro-inflammatory and immunoregulatory networks and is likely involved in the development and progression of radiation-induced pneumonitis In addition, TNF-α stimulates the proliferation of fibroblasts and the secretion of proinflammatory cytokines, including IL-1 and IL-6, from neutrophils and macrophages IL-6 plays an important role in the formation and proliferation of fibrous connective tissue, potentially by increasing collagen aggregation, inhibiting extracellular matrix ECM degradation, and stimulating fibroblast proliferation. Previous studies have suggested that IL-6 leads to inflammation and fibrosis associated with hypersensitivity pneumonitis in mice. These results suggest a close relationship in IL-6 and pneumonitis and fibrotic development IL may inhibit monocytes, macrophages, and Th1 cells as well as enhance B-cell immune regulation function In addition, IL is a T-cell-derived cytokine of the Th-2 family that suppresses inflammation by inhibiting numerous pro-inflammatory cytokines Findings of Barbarin et al have shown that silica-induced pneumonia and pulmonary fibrosis in mice caused the overexpression of IL, thereby contributing to the increased lung damage caused by fibrosis To investigate the effects of EGCG treatment on systemic inflammation, we measured the serum levels of key inflammatory cytokines including TGF-β1, IL-6, IL, and TNF-α. These cytokines were significantly reduced in the EGCG-treated animals compared with the untreated and steroid-treated rats, and this effect lasted for months after treatment ceased. The lower alveolitis score of the EGCG-treated rats also suggested that EGCG reduces the infiltration of inflammatory immune cells. Results of this study are in agreement with those of previous studies that have shown significant anti-inflammatory effects from the administration of EGCG 10 , 35 , This study also investigated the protective effect of EGCG on AE2 cells. AE2 and vascular endothelial cells are the two major targets of radiation-induced lung injury from inflammation and oxidative stress. Results of the SPB staining analysis in the lung revealed that EGCG-treated rats showed a more normalized distribution of AE2 cells in the parenchyma compared with radiation-only and DEX-treated rats. AE2 cells were abundant in alveolar walls of the lung tissues of the EGCG-treated rats, although no evidence of dysplasia was found. These results suggest that EGCG protected parenchymal and AE2 cells from free radical damage. In addition, the myofibroblast proliferation in the lung as demonstrated by α-SMA staining observed in the radiation-only and DEX-treated groups was significantly reduced in rats treated with EGCG at 60 and days after irradiation, suggesting that EGCG-inhibited pulmonary fibrosis partially inhibits myofibroblast transformation and proliferation. We also examined whether EGCG improves the ability of the endogenous oxidative stress response system by activating Nrf2 and its downstream antioxidant enzymes. Sriram et al investigated the protective effects of EGCG in a bleomycin-induced acute lung injury animal model and presented the first evidence that EGCG protection against lung injury is associated with the Nrf2-based activation of the oxidative stress response Nrf2 plays a critical role in the regulation of the major antioxidant enzymes HO-1 and NQO Sahin et al 37 reported that EGCG significantly reduced the production of peroxides and the subsequent peroxidation of lipids by enhancing the expression of antioxidant enzymes e. Those authors also showed that EGCG may increase the downstream expression of other antioxidant enzymes by activating Nrf2 and HO-1, thereby regulating oxidative stress. Our western blot analysis results revealed that EGCG significantly enhanced the expression levels of Nrf-2, HO-1, and NQO-1 in rat lung tissues compared with radiation-only and DEX-treated rats, thereby confirming the results of Sriram et al and Sahin et al 12 , 37 as well as supporting our hypothesis that EGCG relieves oxidative stress by activating Nrf2 and its associated antioxidant enzymes. Since glucocorticosteroids are commonly used to treat irradiation-induced pulmonary fibrosis and other forms of lung fibrosis in humans, DEX was selected as a baseline to compare the efficacy of EGCG using various measures of lung inflammation, the oxidative stress response, and fibrosis. A marginal effectiveness was achieved with DEX therapy at 15 and 30 days post-irradiation; however, these improvements ceased following discontinuing steroid therapy i. The measures of lung inflammation, oxidative stress, and fibrosis among the DEX-treated rats were similar to those of the radiation-only group at 60 and days post-irradiation, suggesting a lack of persistent therapeutic effects. Conversely, our results demonstrate that EGCG was superior to glucocorticoids with regard to reducing inflammation, fibrosis, and oxidative stress during the treatment period which ended at 30 days post-irradiation. In addition, the therapeutic effects of EGCG were sustained even after treatment ceased, unlike the steroid treatment. Collectively, results of the present study have shown that EGCG treatment provides strong, persistent antioxidant, anti-inflammatory, and anti-proliferative effects that protect against irradiation-induced pulmonary fibrosis in rats. EGCG also inhibited myofibroblast proliferation and AE2 cell dysplasia, presumably by suppressing the secretion of TGF-β1. Of note, the findings demonstrate that these effects reduced the rates of morbidity and mortality compared with those among the rats in the DEX group. This study was mainly supported by grants from the National Natural Science Foundation of China NSFC contract nos. CWS11J to H. and was partially supported by other grants from the NSFC NSFC no. and NSFC contract no. and by grants from the Chongqing Science and Technology Commission contract no. RPCD to H. and the Beijing Fengtai Local Government to H. Almeida C, Nagarajan D, Tian J, et al: The role of alveolar epithelium in radiation-induced lung injury. PLoS One. Epperly MW, Guo H, Gretton JE and Greenberger JS: Bone marrow origin of myofibroblasts in irradiation pulmonary fibrosis. Am J Respir Cell Mol Biol. Matsuo Y, Shibuya K, Nakamura M, et al: Dose-volume metrics associated with radiation pneumonitis after stereotactic body radiation therapy for lung cancer. Int J Radiat Oncol Biol Phys. Minor GI, Yashar CM, Spanos WJ Jr, et al: The relationship of radiation pneumonitis to treated lung volume in breast conservation therapy. Breast J. Rosenzweig KE, Zauderer MG, Laser B, et al: Pleural intensity-modulated radiotherapy for malignant pleural mesothelioma. Zhang Y, Zhang X, Rabbani ZN, Jackson IL and Vujaskovic Z: Oxidative stress mediates radiation lung injury by inducing apoptosis. Mak JC: Potential role of green tea catechins in various disease therapies: progress and promise. Clin Exp Pharmacol Physiol. Li CP, Yao J, Tao ZF, Li XM, Jiang Q and Yan B: Epigallocatechin-gallate EGCG regulates autophagy in human retinal pigment epithelial cells: a potential role for reducing UVB light-induced retinal damage. Biochem Biophys Res Commun. J Immunol. |
| Related products | In rezpiratory vitro studies, EGCG decreases the expression Liver detoxification diet Digestive health supplements induced Liver detoxification diet nicotine 60human papillomavirus HPV oncoprotein 66or insulin-like growth factor 1 IGF-1 EGCG treatment reduced Extradt mortality rate and lung index heapth, alleviated lung histological damage, reduced collagen deposition, modulated the redox state of serum, inhibited myo fibroblast proliferation, protected AE2 cells, and regulated the serum levels of TGF-β1, IL-6, IL, and TNF-α. Research suggests that green tea may help arthritis by reducing inflammation and slowing the breakdown of cartilage. Hu J, Huang Y, Xiong M, Luo S, Chen Y, Li Y. Liu Y, Wu Z, Cheng L, Zhang X, Yang H. Ryu OH, Lee J, Lee KW, et al. |
| Products mentioned in this post | Compared with healthy individuals, the fecal microbiome of COVID patients has significantly changed. Los M, Schenk H, Hexel K, Baeuerle PA, Droge W, Schulze-Osthoff K: IL-2 gene expression and NF-kappa B activation through CD28 requires reactive oxygen production by 5-lipoxygenase. What, then, is the mechanism by which green tea extract reduces acute inflammation? Article CAS PubMed PubMed Central Google Scholar Chan MMY, Ho CT, Huang HI: Effects of three dietary phytochemicals from tea, rosemary and turmeric on inflammation-induced nitrite production. Fujita H, Yamagami T. In addition, several other pathways also mediate the antiproliferation and proapoptosis of lung cancer. |
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