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International Journal of Molecular... Apr 2022Hypoxia-induced neuroinflammation in stroke, neonatal hypoxic encephalopathy, and other diseases subsequently contributes to neurological damage and neuronal diseases....
Hypoxia-induced neuroinflammation in stroke, neonatal hypoxic encephalopathy, and other diseases subsequently contributes to neurological damage and neuronal diseases. Microglia are the primary neuroimmune cells that play a crucial role in cerebral inflammation. Epigallocatechin gallate (EGCG) has a protective antioxidant and anti-inflammatory effects against neuroinflammation. However, the effects of EGCG on hypoxia-induced inflammation in microglia and the underlying mechanism remain unclear. In this study, we investigated whether EGCG might have a protective effect against hypoxia injury in microglia by treatment with CoCl to establish a hypoxic model of BV2 microglia cells following EGCG pre-treatment. An exposure of cells to CoCl caused an increase in inflammatory mediator interleukin (IL)-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 expression, which were significantly ameliorated by EGCG via inhibition of NF-κB pathway. In addition, EGCG attenuated the expression of hypoxia-inducible factor (HIF)-1α and the generation of ROS in hypoxic BV2 cells. Furthermore, the suppression of hypoxia-induced IL-6 production by EGCG was mediated via the inhibition of HIF-1α expression and the suppression of ROS generation in BV2 cells. Notably, EGCG increased the Nrf-2 levels and HO-1 levels in the presence of CoCl. Additionally, EGCG suppressed hypoxia-induced apoptosis of BV2 microglia with cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-3. In summary, EGCG protects microglia from hypoxia-induced inflammation and oxidative stress via abrogating the NF-κB pathway as well as activating the Nrf-2/HO-1 pathway.
Topics: Humans; Catechin; Cyclooxygenase 2; Hypoxia, Brain; Inflammation; Interleukin-6; Lipopolysaccharides; Microglia; NF-kappa B; Reactive Oxygen Species
PubMed: 35409364
DOI: 10.3390/ijms23074004 -
Aging Cell Sep 2020We have recently reported that epigallocatechin gallate (EGCG) could extend lifespan in healthy rats. This study aimed to investigate the effects and mechanisms of a... (Randomized Controlled Trial)
Randomized Controlled Trial
The phytochemical epigallocatechin gallate prolongs the lifespan by improving lipid metabolism, reducing inflammation and oxidative stress in high-fat diet-fed obese rats.
We have recently reported that epigallocatechin gallate (EGCG) could extend lifespan in healthy rats. This study aimed to investigate the effects and mechanisms of a high dose of EGCG in extending the lifespan of obese rats. Ninety adult male Wistar rats were randomly divided into the control (NC), high-fat (HF) and EGCG groups. Serum glucose and lipids, inflammation and oxidative stress were dynamically determined from adulthood to death, and the transcriptome and proteome of the liver were also examined. The median lifespans of the NC, HF and EGCG groups were 693, 599 and 683 days, respectively, and EGCG delayed death by 84 days in obese rats. EGCG improved serum glucose and lipids and reduced inflammation and oxidative stress associated with aging in obese rats induced by a high-fat diet. EGCG also significantly decreased the levels of total free fatty acids (FFAs), SFAs and the n-6/n-3 ratio but significantly increased the n-3 FFAs related to longevity. The joint study of the transcriptome and proteome in liver found that EGCG exerted its effects mainly by regulating the suppression of hydrogen peroxide and oxygen species metabolism, suppression of oxidative stress, activation of fatty acid transport and oxidation and cholesterol metabolism. EGCG significantly increased the protein expression of FOXO1, Sirt1, CAT, FABP1, GSTA2, ACSL1 and CPT2 but significantly decreased NF-κB, ACC1 and FAS protein levels in the livers of rats. All the results indicate that EGCG extends lifespan by improving FFA metabolism and reducing the levels of inflammatory and oxidative stress in obese rats.
Topics: Animals; Catechin; Diet, High-Fat; Humans; Inflammation; Lipid Metabolism; Longevity; Male; Obesity; Oxidative Stress; Phytochemicals; Rats; Rats, Wistar
PubMed: 32729662
DOI: 10.1111/acel.13199 -
Food Chemistry Nov 2021Inhibition of maltase, sucrase, isomaltase and glucoamylase activity by acarbose, epigallocatechin gallate, epicatechin gallate and four polyphenol-rich tea extract from...
Inhibition of maltase, sucrase, isomaltase and glucoamylase activity by acarbose, epigallocatechin gallate, epicatechin gallate and four polyphenol-rich tea extract from white, green, oolong, black tea, were investigated by using rat intestinal enzymes and human Caco-2 cells. Regarding rat intestinal enzyme mixture, all four tea extracts were very effective in inhibiting maltase and glucoamylase activity, but only white tea extract inhibited sucrase and isomaltase activity and the inhibition was limited. Mixed-type inhibition on rat maltase activity was observed. Tea extracts in combination with acarbose, produced a synergistic inhibitory effect on rat maltase activity. Caco-2 cells experiments were conducted in Transwells. Green tea extract and epigallocatechin gallate show dose-dependent inhibition on human sucrase activity, but no inhibition on rat sucrase activity. The opposite was observed on maltase activity. The results highlighted the different response in the two investigated model systems and show that tea polyphenols are good inhibitors for α-glucosidase activity.
Topics: Acarbose; Animals; Caco-2 Cells; Catechin; Glucan 1,4-alpha-Glucosidase; Glycoside Hydrolase Inhibitors; Glycoside Hydrolases; Humans; Intestines; Kinetics; Oligo-1,6-Glucosidase; Plant Extracts; Polyphenols; Rats; Sucrase; Tea; alpha-Glucosidases
PubMed: 34029903
DOI: 10.1016/j.foodchem.2021.130047 -
Phytomedicine : International Journal... Oct 2023Epigallocatechin gallate (EGCG) has multiple biological effects such as anti-tumor multiple drug resistance, antioxidation and anti-inflammatory properties. Ferroptosis...
BACKGROUND
Epigallocatechin gallate (EGCG) has multiple biological effects such as anti-tumor multiple drug resistance, antioxidation and anti-inflammatory properties. Ferroptosis is the main driving factor of ischemic heart injury, thus inhibiting ferroptosis may prove to be an effective treatment strategy for cardiovascular diseases. However, the role of EGCG on ferroptosis in ischemic myocardium and underlying mechanisms remain uncertain.
PURPOSE
This study was aimed to investigate the effects and potential mechanisms of EGCG on myocardial ischemic-induced ferroptosis both in vitro and in vivo.
METHODS
Cardiomyocyte hypoxia model and mouse acute myocardial infarction (AMI) model were established in vitro and in vivo. MiR-450b-5p and ACSL4 silencing or overexpression plasmids were transfected, with or without EGCG pretreatment. Cell viability was determined by the CCK-8 assay. Hematoxylin and eosin (HE) staining and transmission electron microscopy (TEM) were used to evaluate the morphologic alterations. TTC staining was used to observe the infarction area, and echocardiography was adopted to appraise the heart function. Using flow cytometry, the presence of reactive oxygen species (ROS) was assessed. The content of cardiac troponin I (cTn I), glutathione (GSH), malondialdehyde (MDA), divalent iron ions (Fe) and superoxide dismutase (SOD) were detected using reagent kits. A luciferase activity assay was performed to assess the binding ability of miR-450b-5p to ACSL4. Expressions of related genes and proteins were measured by RT-qPCR and western blotting respectively.
RESULTS
EGCG attenuated AMI-induced ferroptosis and improved myocardial ischemia injury, which was associated with reducing iron deposition and cTn I, inhibition of lipid peroxidation, decreasing TFR1 and ACSL4, and upregulating SLC7A11, FTH1 and GPX4. Meanwhile, EGCG pretreatment increased miR-450b-5p expression in ischemic myocardium. Further researches discovered that knockdown of miR-450b-5p partially compromised EGCG-generated protective effect in hypoxia HL-1 cells, while combination with miR-450b-5p mimic could strengthen the potency of EGCG on ischemic myocardium. The dual-luciferase test demonstrated that miR-450b-5p has binding to ACSL4. Furthermore, silencing of ACSL4 synergistically increased the cardioprotective effect of EGCG. More significantly, EGCG treatment regulated the ferroptosis-related proteins expression via miR-450b-5p/ACSL4 axis.
CONCLUSION
In summary, the present study evidently demonstrated that EGCG attenuates myocardial ischemia injury by targeting ferroptosis. Our work revealed the role of miR-450b-5p/ACSL4 axis in AMI for the first time. Further, it also elucidated the molecular mechanisms of EGCG on inhibiting ferroptosis greatly depend on the miR-450b-5p/ACSL4 axis, suggesting that EGCG may act as a novel anti-ferroptosis agent and exert a therapeutic role in AMI.
Topics: Animals; Mice; Myocardial Infarction; Myocardial Ischemia; Catechin; Disease Models, Animal; MicroRNAs
PubMed: 37597361
DOI: 10.1016/j.phymed.2023.154999 -
The Journal of Pharmacy and Pharmacology Mar 2021We and others have previously shown that epigallocatechin gallate (EGCg) inhibits the activity of an important virulence factor, leukotoxin (LtxA), produced by the oral...
OBJECTIVES
We and others have previously shown that epigallocatechin gallate (EGCg) inhibits the activity of an important virulence factor, leukotoxin (LtxA), produced by the oral bacterium Aggregatibacter actinomycetemcomitans, suggesting the potential use of this molecule as an anti-virulence strategy to treat periodontal infections. Here, we sought to better understand the effects of EGCg on toxin secretion and A. actinomycetemcomitans pathogenicity in a co-culture model.
METHODS
We used a quantitative immunoblot assay to determine the concentrations of LtxA in the bacterial supernatant and on the bacterial cell surface. Using a co-culture model, consisting of A. actinomycetemcomitans and THP-1 cells, we studied the impact of EGCg-mediated changes in LtxA secretion on the toxicity of A. actinomycetemcomitans.
KEY FINDINGS
EGCg increased production of LtxA and changed the localization of secreted LtxA from the supernatant to the surface of the bacterial cells. In the co-culture model, a single low dose of EGCg did not protect host THP-1 cells from A. actinomycetemcomitans-mediated cytotoxicity, but a multiple dosing strategy had improved effects.
CONCLUSIONS
Together, these results demonstrate that EGCg has important, but complicated, effects on toxin secretion and activity; new dosing strategies and comprehensive model systems may be required to properly develop these anti-virulence activities.
Topics: Aggregatibacter actinomycetemcomitans; Anti-Bacterial Agents; Bacterial Toxins; Catechin; Coculture Techniques; Dose-Response Relationship, Drug; Exotoxins; Humans; Periodontitis; Virulence
PubMed: 33793838
DOI: 10.1093/jpp/rgaa051 -
Journal of Immunology Research 2018Immune dysfunction is caused by various factors, including changes in relevant immune regulators and environmental stress. Immune system imbalance leads to a variety of... (Review)
Review
Immune dysfunction is caused by various factors, including changes in relevant immune regulators and environmental stress. Immune system imbalance leads to a variety of diseases in humans. Nutrition may play an essential role in immunity by interfering with proinflammatory cytokine synthesis, immune cell regulation, and gene expression. Polyphenols, one of many categories of natural substances, exhibit a range of biological activities. Polyphenols promote immunity to foreign pathogens via various pathways. Different immune cells express multiple types of polyphenol receptors that recognise and allow cellular uptake of polyphenols, which subsequently activate signalling pathways to initiate immune responses. Furthermore, the polyphenols curcumin and epigallocatechin gallate can induce epigenetic changes in cells. In summary, polyphenols can be used to regulate intestinal mucosal immune responses, allergic diseases, and antitumour immunity.
Topics: Animals; Catechin; Curcumin; Epigenesis, Genetic; Humans; Hypersensitivity; Immunity; Immunomodulation; Inflammation; Neoplasms; Nutritional Physiological Phenomena; Oxidative Stress; Polyphenols; Signal Transduction
PubMed: 29850614
DOI: 10.1155/2018/1264074 -
Nutrients Dec 2018Green tea is a beverage that is widely consumed worldwide and is believed to exert effects on different diseases, including cancer. The major components of green tea are... (Review)
Review
Green tea is a beverage that is widely consumed worldwide and is believed to exert effects on different diseases, including cancer. The major components of green tea are catechins, a family of polyphenols. Among them, epigallocatechin-gallate (EGCG) is the most abundant and biologically active. EGCG is widely studied for its anti-cancer properties. However, the cellular and molecular mechanisms explaining its action have not been completely understood, yet. EGCG is effective in vivo at micromolar concentrations, suggesting that its action is mediated by interaction with specific targets that are involved in the regulation of crucial steps of cell proliferation, survival, and metastatic spread. Recently, several proteins have been identified as EGCG direct interactors. Among them, the trans-membrane receptor 67LR has been identified as a high affinity EGCG receptor. 67LR is a master regulator of many pathways affecting cell proliferation or apoptosis, also regulating cancer stem cells (CSCs) activity. EGCG was also found to be interacting directly with Pin1, TGFR-II, and metalloproteinases (MMPs) (mainly MMP2 and MMP9), which respectively regulate EGCG-dependent inhibition of NF-kB, epithelial-mesenchimal transaction (EMT) and cellular invasion. EGCG interacts with DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), which modulates epigenetic changes. The bulk of this novel knowledge provides information about the mechanisms of action of EGCG and may explain its onco-suppressive function. The identification of crucial signalling pathways that are related to cancer onset and progression whose master regulators interacts with EGCG may disclose intriguing pharmacological targets, and eventually lead to novel combined treatments in which EGCG acts synergistically with known drugs.
Topics: Camellia sinensis; Catechin; DNA Methylation; Humans; Metalloproteases; Methyltransferases; NIMA-Interacting Peptidylprolyl Isomerase; Neoplasms; Phytotherapy; Plant Extracts; Polyphenols; Receptors, Cell Surface; Signal Transduction; Tea
PubMed: 30563268
DOI: 10.3390/nu10121936 -
Biomolecules Oct 2020Green tea and its major bioactive component, (-)-epigallocatechin gallate (EGCG), possess diverse biological properties, particularly antiproliferation, antimetastasis,... (Review)
Review
Green tea and its major bioactive component, (-)-epigallocatechin gallate (EGCG), possess diverse biological properties, particularly antiproliferation, antimetastasis, and apoptosis induction. Many studies have widely investigated the anticancer and synergistic effects of EGCG due to the side effects of conventional cytotoxic agents. This review summarizes recent knowledge of underlying mechanisms of EGCG on protective roles for endometrial, breast, and ovarian cancers based on both in vitro and in vivo animal studies. EGCG has the ability to regulate many pathways, including the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), inhibition of nuclear factor-κB (NF-κB), and protection against epithelial-mesenchymal transition (EMT). EGCG has also been found to interact with DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), which affect epigenetic modifications. Finally, the action of EGCG may exert a suppressive effect on gynecological cancers and have beneficial effects on auxiliary therapies for known drugs. Thus, future clinical intervention studies with EGCG will be necessary to more and clear evidence for the benefit to these cancers.
Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Catechin; Endometrial Neoplasms; Epithelial-Mesenchymal Transition; Female; Humans; NF-E2-Related Factor 2; Ovarian Neoplasms; Protective Agents; Tea
PubMed: 33113766
DOI: 10.3390/biom10111481 -
European Journal of Medicinal Chemistry Dec 2023Epigallocatechin gallate (EGCG) is a polyphenol present in green tea (Camellia sinensis), which has revealed anti-cancer effects toward a variety of cancer cells in... (Review)
Review
Epigallocatechin gallate (EGCG) is a polyphenol present in green tea (Camellia sinensis), which has revealed anti-cancer effects toward a variety of cancer cells in vitro and protective potential against neurodegenerative diseases such as Alzheimer's and Parkinson's. Unfortunately, EGCG presents disappointing bioavailability after oral administration, primarily due to its chemical instability and poor absorption. Due to these limitations, EGCG is currently not used in medication, but only as a dietary supplement in the form of green tea extract. Therefore, it needs further modifications before being considered suitable for extensive medical applications. In this article, we review the scientific literature about EGCG derivatives focusing on their biological properties and potential medical applications. The most common chemical modifications of epigallocatechin gallate rely on introducing fatty acid chains or sugar molecules to its chemical structure to modify solubility. Another frequently employed procedure is based on blocking EGCG's hydroxyl groups with various substituents. Novel derivatives reveal interesting properties, of which, antioxidant, anti-inflammatory, antitumor and antimicrobial, are especially important. It is worth noting that the most promising EGCG derivatives present higher stability and activity than base EGCG.
Topics: Polyphenols; Catechin; Tea; Camellia sinensis; Antioxidants
PubMed: 37776575
DOI: 10.1016/j.ejmech.2023.115820 -
Nutrients Feb 2024The most common malignant gynecologic diseases are cervical, uterine, ovarian, vaginal, and vulvar cancer. Among them, ovarian cancer causes more deaths than any other... (Review)
Review
The most common malignant gynecologic diseases are cervical, uterine, ovarian, vaginal, and vulvar cancer. Among them, ovarian cancer causes more deaths than any other cancer of the female reproductive system. A great number of women suffer from endometriosis, uterine fibroids (UFs), adenomyosis, dysmenorrhea, and polycystic ovary syndrome (PCOS), which are widespread benign health problems causing troublesome and painful symptoms and significantly impairing the quality of life of affected women, and they are some of the main causes of infertility. In addition to the available surgical and pharmacological options, the effects of supporting standard treatment with naturally occurring compounds, mainly polyphenols, are being studied. Catechins are responsible for the majority of potential health benefits attributed to green tea consumption. Epigallocatechin gallate (EGCG) is considered a non-toxic, natural compound with potential anticancer properties. Antioxidant action is its most common function, but attention is also drawn to its participation in cell division inhibition, apoptosis stimulation and epigenetic regulation. In this narrative review, we describe the role of EGCG consumption in preventing the development of benign reproductive disorders such as UF, endometriosis, and PCOS, as well as malignant gynecologic conditions. We discuss possible epigenetic mechanisms that may be related to the action of EGCG.
Topics: Female; Humans; Endometriosis; Epigenesis, Genetic; Polycystic Ovary Syndrome; Quality of Life; Catechin; Tea; Leiomyoma
PubMed: 38398883
DOI: 10.3390/nu16040559