-
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 -
Molecular Cancer Jun 2023Clinical hyperthermic intraperitoneal chemotherapy (HIPEC) is regarded as a potential treatment that can prolong survival of patients with peritoneal metastases after...
Clinical hyperthermic intraperitoneal chemotherapy (HIPEC) is regarded as a potential treatment that can prolong survival of patients with peritoneal metastases after cytoreductive surgery. However, treated tumor cells are prone to becoming heat resistant to HIPEC therapy through high expression of heat shock proteins (HSPs). Here, a carrier-free bifunctional nanoinhibitor was developed for HIPEC therapy in the management of peritoneal metastases. Self-assembly of the nanoinhibitor was formed by mixing Mn ion and epigallocatechin gallate (EGCG) in a controllable manner. Such nanoinhibitor directly inhibited HSP90 and impaired the HSP90 chaperone cycle by reduced intracellular ATP level. Additionally, heat and Mn ion synergistically induced oxidative stress and expression of caspase 1, which activated GSDMD by proteolysis and caused pyroptosis in tumor cells, triggering immunogenic inflammatory cell death and induced maturation of dendritic cells through the release of tumor antigens. This strategy to inhibit heat resistance in HIPEC presented an unprecedented paradigm for converting "cold" tumors into "hot" ones, thus significantly eradicating disseminated tumors located deep in the abdominal cavity and stimulating immune response in peritoneal metastases of a mouse model. Collectively, the nanoinhibitor effectively induced pyroptosis of colon tumor cells under heat conditions by inhibiting heat stress resistance and increasing oxidative stress, which may provide a new strategy for treatment of colorectal peritoneal metastases.
Topics: Animals; Mice; Hyperthermic Intraperitoneal Chemotherapy; Peritoneal Neoplasms; HSP90 Heat-Shock Proteins; Proteolysis; Colon
PubMed: 37316830
DOI: 10.1186/s12943-023-01790-2 -
Molecules (Basel, Switzerland) Jul 2023Cellular signaling pathways involved in the maintenance of the equilibrium between cell proliferation and apoptosis have emerged as rational targets that can be... (Review)
Review
Cellular signaling pathways involved in the maintenance of the equilibrium between cell proliferation and apoptosis have emerged as rational targets that can be exploited in the prevention and treatment of cancer. Epigallocatechin-3-gallate (EGCG) is the most abundant phenolic compound found in green tea. It has been shown to regulate multiple crucial cellular signaling pathways, including those mediated by EGFR, JAK-STAT, MAPKs, NF-κB, PI3K-AKT-mTOR, and others. Deregulation of the abovementioned pathways is involved in the pathophysiology of cancer. It has been demonstrated that EGCG may exert anti-proliferative, anti-inflammatory, and apoptosis-inducing effects or induce epigenetic changes. Furthermore, preclinical and clinical studies suggest that EGCG may be used in the treatment of numerous disorders, including cancer. This review aims to summarize the existing knowledge regarding the biological properties of EGCG, especially in the context of cancer treatment and prophylaxis.
Topics: Humans; Signal Transduction; Phosphatidylinositol 3-Kinases; Neoplasms; NF-kappa B; Tea; Catechin; Apoptosis
PubMed: 37446908
DOI: 10.3390/molecules28135246 -
Heliyon Feb 2024Small molecule natural compounds are gaining popularity in biomedicine due to their easy access to wide structural diversity and their proven health benefits in several... (Review)
Review
Small molecule natural compounds are gaining popularity in biomedicine due to their easy access to wide structural diversity and their proven health benefits in several case studies. Affinity measurements of small molecules below 100 Da molecular weight in a label-free and automatized manner using small amounts of samples have now become a possibility and reviewed in the present work. We also highlight novel label-free setups with excellent time resolution, which is important for kinetic measurements of biomolecules and living cells. We summarize how molecular-scale affinity data can be obtained from the in-depth analysis of cellular kinetic signals. Unlike traditional measurements, label-free biosensors have made such measurements possible, even without the isolation of specific cellular receptors of interest. Throughout this review, we consider epigallocatechin gallate (EGCG) as an exemplary compound. EGCG, a catechin found in green tea, is a well-established anti-inflammatory and anti-cancer agent. It has undergone extensive examination in numerous studies, which typically rely on fluorescent-based methods to explore its effects on both healthy and tumor cells. The summarized research topics range from molecular interactions with proteins and biological films to the kinetics of cellular adhesion and movement on novel biomimetic interfaces in the presence of EGCG. While the direct impact of small molecules on living cells and biomolecules is relatively well investigated in the literature using traditional biological measurements, this review also highlights the indirect influence of these molecules on the cells by modifying their nano-environment. Moreover, we underscore the significance of novel high-throughput label-free techniques in small molecular measurements, facilitating the investigation of both molecular-scale interactions and cellular processes in one single experiment. This advancement opens the door to exploring more complex multicomponent models that were previously beyond the reach of traditional assays.
PubMed: 38371993
DOI: 10.1016/j.heliyon.2024.e25603 -
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 -
Antioxidants (Basel, Switzerland) Aug 2023The global increase in the incidence of kidney failure constitutes a major public health problem. Kidney disease is classified into acute and chronic: acute kidney... (Review)
Review
The global increase in the incidence of kidney failure constitutes a major public health problem. Kidney disease is classified into acute and chronic: acute kidney injury (AKI) is associated with an abrupt decline in kidney function and chronic kidney disease (CKD) with chronic renal failure for more than three months. Although both kidney syndromes are multifactorial, inflammation and oxidative stress play major roles in the diversity of processes leading to these kidney malfunctions. Here, we reviewed various publications on medicinal plants with antioxidant and anti-inflammatory properties with the potential to treat and manage kidney-associated diseases in rodent models. Additionally, we conducted a meta-analysis to identify gene signatures and associated biological processes perturbed in human and mouse cells treated with antioxidants such as epigallocatechin gallate (EGCG), the active ingredient in green tea, and the mushroom Ganoderma lucidum (GL) and in kidney disease rodent models. We identified EGCG- and GL-regulated gene signatures linked to metabolism; inflammation (NRG1, E2F1, NFKB1 and JUN); ion signalling; transport; renal processes (SLC12A1 and LOX) and VEGF, ERBB and BDNF signalling. Medicinal plant extracts are proving to be effective for the prevention, management and treatment of kidney-associated diseases; however, more detailed characterisations of their targets are needed to enable more trust in their application in the management of kidney-associated diseases.
PubMed: 37627594
DOI: 10.3390/antiox12081599 -
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 -
International Journal of Molecular... Sep 2023The natural flavonoid epigallocatechin gallate has a wide range of biological activities, including being capable of binding to nucleic acids; however, the mechanisms of...
The natural flavonoid epigallocatechin gallate has a wide range of biological activities, including being capable of binding to nucleic acids; however, the mechanisms of the interactions of epigallocatechin gallate with DNA organized in chromatin have not been systematically studied. In this work, the interactions of epigallocatechin gallate with chromatin in cells and with nucleosomes and chromatosomes in vitro were studied using fluorescent microscopy and single-particle Förster resonance energy transfer approaches, respectively. Epigallocatechin gallate effectively penetrates into the nuclei of living cells and binds to DNA there. The interaction of epigallocatechin gallate with nucleosomes in vitro induces a large-scale, reversible uncoiling of nucleosomal DNA that occurs without the dissociation of DNA or core histones at sub- and low-micromolar concentrations of epigallocatechin gallate. Epigallocatechin gallate does not reduce the catalytic activity of poly(ADP-ribose) polymerase 1, but causes the modulation of the structure of the enzyme-nucleosome complex. Epigallocatechin gallate significantly changes the structure of chromatosomes, but does not cause the dissociation of the linker histone. The reorganization of nucleosomes and chromatosomes through the use of epigallocatechin gallate could facilitate access to protein factors involved in DNA repair, replication and transcription to DNA and, thus, might contribute to the modulation of gene expression through the use of epigallocatechin gallate, which was reported earlier.
Topics: Nucleosomes; Chromatin; Histones; DNA
PubMed: 37762491
DOI: 10.3390/ijms241814187 -
Nutrients Dec 2023Uterine fibroids are benign tumors that arise from the smooth muscle tissue of the uterus and are the most common tumors in women. Due to their high prevalence, costs... (Review)
Review
Uterine fibroids are benign tumors that arise from the smooth muscle tissue of the uterus and are the most common tumors in women. Due to their high prevalence, costs for the health care system and the substantial impact on women's quality of life, they are a significant public health concern. Previous literature on the impact of diet on the occurrence, growth and symptoms of fibroids is limited. Recently, many papers have been written on this topic. A scoping review of PubMed and Cochrane databases was performed using the following keywords: uterine fibroids, antioxidants, diet, diet, vegetarian, vegetables, fruits, meat and soy foods, dairy products, tea, vitamin D, vitamin C, ascorbic acid. Preliminary research has shown a beneficial effect of vegetable and fruit consumption on the occurrence of fibroids. A relationship between hypovitaminosis D and an increased risk of fibroids has also been demonstrated. Studies on epigallocatechin gallate showed its apoptosis-promoting and antifibrinolytic effect in fibroid cells. Initial results are promising, but further randomized trials are needed to draw firm conclusions about the effects of diet and nutrients on uterine fibroids.
Topics: Female; Humans; Uterine Neoplasms; Quality of Life; Leiomyoma; Vitamins; Diet; Vegetables; Ascorbic Acid
PubMed: 38068842
DOI: 10.3390/nu15234984