Epigallocatechin-3-gallate protects sepsis‐induced myocardial dysfunction by inhibiting the nuclear factor-κB signaling pathway
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ABSTRACT:
SUBMITTER: Chen B
PROVIDER: S-EPMC10915574 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
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Project description:Cardiac tissue damage following ischemia leads to cardiomyocyte apoptosis and myocardial fibrosis. Epigallocatechin-3-gallate (EGCG), an active polyphenol flavonoid or catechin, exerts bioactivity in tissues with various diseases and protects ischemic myocardium; however, its association with the endothelial-to-mesenchymal transition (EndMT) is unknown. Human umbilical vein endothelial cells (HUVECs) pretreated with transforming growth factor β2 (TGF-β2) and interleukin 1β (IL-1β) were treated with EGCG to verify cellular function. In addition, EGCG is involved in RhoA GTPase transmission, resulting in reduced cell mobility, oxidative stress, and inflammation-related factors. A mouse myocardial infarction (MI) model was used to confirm the association between EGCG and EndMT in vivo. In the EGCG-treated group, ischemic tissue was regenerated by regulating proteins involved in the EndMT process, and cardioprotection was induced by positively regulating apoptosis and fibrosis of cardiomyocytes. Furthermore, EGCG can reactivate myocardial function due to EndMT inhibition. In summary, our findings confirm that EGCG is an impact activator controlling the cardiac EndMT process derived from ischemic conditions and suggest that supplementation with EGCG may be beneficial in the prevention of cardiovascular disease.
| S-EPMC10215739 | biostudies-literature
Project description:Cardiac dysfunction is a well-recognized complication of sepsis and seriously affects the prognosis of sepsis patients. IL-30 has been reported to exert anti-inflammatory effects in various diseases. However, the role of IL-30 in sepsis-induced myocardial dysfunction (SIMD) remains unclear. Here, we explored the protective role of IL-30 in cecum ligation and puncture (CLP)-induced SIMD mice. IL-30 expression increased in the cardiac tissues of septic mice and was mainly derived from macrophages. IL-30 deletion or neutralization aggravated sepsis-induced cardiac dysfunction and injury, whereas recombinant IL-30 treatment significantly ameliorated it. Mechanistically, IL-30 deficiency exerts pro-inflammatory effects by promoting Ly6Chigh macrophage polarization and pyroptosis. Inhibiting NLRP3 with MCC950 significantly reversed cardiac dysfunction, macrophage polarization and pyroptosis aggravated by IL-30 deficiency. Recombinant IL-30 inhibited pro-inflammatory macrophage polarization and pyroptosis in vivo and vitro. Taken together, these results suggest that IL-30 protects against SIMD by inhibiting pro-inflammatory macrophage polarization and pyroptosis.
| S-EPMC10450523 | biostudies-literature
Project description:BackgroundIntervertebral disc degeneration (IDD) is the most common diagnosis of patients with lower back pain. IDD is the underlying lesion of many spinal degenerative diseases; however, the role of cGAS/Sting/NLRP3 pathway and epigallocatechin gallate (EGCG) in the development of IDD remained unclear.MethodsThe expressions of cGAS, Sting and NLRP3 mRNA of intervertebral disc (IVD) samples from IDD patients and controls were detected by RT-PCR. The nucleus pulposus cells (NPCs) were induced by hydrogen peroxide (H2O2) and used as an in-vitro model. Both 5 ?M and 25 ?M EGCG treatment were used to detect the effect of EGCG on the in-vitro model. Cell viability was detected by the MTT method, and cell apoptosis and cell cycle would be detected by flow cytometry. Western blot was used in the detection of the expression of cGAS/Sting/NLRP3 as well as apoptosis-related protein level. ELISA was used in the detection of pro-inflammatory factors, including IL-1?, TNF-?, IL-6 and IL-10.ResultsThe expressions of cGAS, Sting and NLRP3 mRNA were significantly increased in the IVD samples from IDD patients and NLRP3 was associated with cGAS and Sting. Advanced in-vitro study showed that H2O2 significantly increased the expression of cGAS, Sting and NLRP3 protein levels. Advanced experiments showed that EGCG treatment demonstrated significant protective effects in cell viability, apoptosis, cell cycle arrest and inflammatory status through down-regulation of cGAS/Sting/NLRP3 pathway.ConclusionIt was shown that the cGAS, Sting and NLRP3 up-regulation was associated with the incidence of IDD. Our findings also suggest that EGCG treatment would provide anti-apoptosis, anti-inflammation and promote cell viability in H2O2 treatment-incubated NPCs through inhibiting cGAS/Sting/NLRP3 pathway.
| S-EPMC7266312 | biostudies-literature
Project description: Not available
| S-EPMC7469984 | biostudies-literature
Project description:Hexavalent chromium [Cr(VI)] is a human carcinogen that results in the generation of reactive oxygen species (ROS) and a variety of DNA lesions leading to cell death. Epigallocatechin-3-gallate (EGCG), the major polyphenol present in green tea, possesses potent antioxidative activity capable of protecting normal cells from various stimuli-induced oxidative stress and cell death. Here we demonstrated that co-treatment with EGCG protected human normal bronchial epithelial BEAS-2B cells from Cr(VI)-induced cell death in a dose-dependent manner. Cr(VI) induces apoptosis as the primary mode of cell death. Co-treatment of BEAS-2B cells with EGCG dose-dependently suppressed Cr(VI)-induced apoptosis. Fluorescence microscopic analyses and quantitative measurement revealed that EGCG significantly decreased intracellular levels of ROS induced by Cr(VI) exposure. Using a well-established K(+)/SDS precipitation assay, we further showed that EGCG was able to dose-dependently reduce DNA-protein cross-links (DPC), lesions that could be partially attributed to Cr(VI)-induced oxidative stress. Finally, analyses of Affymetrix microarray containing 28,869 well-annotated genes revealed that, among the 3412 genes changed more than 1.5-fold by Cr(VI) treatment, changes of 2404 genes (70%) were inhibited by pretreatment of EGCG. Real-time PCR confirmed the induction of 3 genes involved in cell death and apoptosis by Cr(VI), which was eliminated by EGCG. In contrast, Cr(VI) reduced the expression of 3 genes related to cellular defense, and this reduction was inhibited by EGCG. Our results indicate that EGCG protects BEAS-2B cells from Cr(VI)-induced cytotoxicity presumably by scavenging ROS and modulating a subset of genes. EGCG, therefore, might serve as a potential chemopreventive agent against Cr(VI) carcinogenesis.
| S-EPMC3259276 | biostudies-literature
Project description:Oxidative stress-related phenotypic changes and a decline in the number of viable cells are crucial contributors to intervertebral disc degeneration. The polyphenol epigallocatechin 3-gallate (EGCG) can interfere with painful disc degeneration by reducing inflammation, catabolism, and pain. In this study, we hypothesized that EGCG furthermore protects against senescence and/or cell death, induced by oxidative stress. Sublethal and lethal oxidative stress were induced in primary human intervertebral disc cells with H2O2 (total n = 36). Under sublethal conditions, the effects of EGCG on p53-p21 activation, proliferative capacity, and accumulation of senescence-associated β-galactosidase were tested. Further, the effects of EGCG on mitochondria depolarization and cell viability were analyzed in lethal oxidative stress. The inhibitor LY249002 was applied to investigate the PI3K/Akt pathway. EGCG inhibited accumulation of senescence-associated β-galactosidase but did not affect the loss of proliferative capacity, suggesting that EGCG did not fully neutralize exogenous radicals. Furthermore, EGCG increased the survival of IVD cells in lethal oxidative stress via activation of prosurvival PI3K/Akt and protection of mitochondria. We demonstrated that EGCG not only inhibits inflammation but also can enhance the survival of disc cells in oxidative stress, which makes it a suitable candidate for the development of novel therapies targeting disc degeneration.
| S-EPMC4826942 | biostudies-literature
Project description:Antioxidant agents are promising pharmaceuticals to prevent salivary gland (SG) epithelial injury from radiotherapy and their associated irreversible dry mouth symptoms. Epigallocatechin-3-gallate (EGCG) is a well-known antioxidant that can exert growth or inhibitory biological effects in normal or pathological tissues leading to disease prevention. The effects of EGCG in the various SG epithelial compartments are poorly understood during homeostasis and upon radiation (IR) injury. This study aims to: (1) determine whether EGCG can support epithelial proliferation during homeostasis; and (2) investigate what epithelial cells are protected by EGCG from IR injury. Ex vivo mouse SG were treated with EGCG from 7.5-30 µg/mL for up to 72 h. Next, SG epithelial branching morphogenesis was evaluated by bright-field microscopy, immunofluorescence, and gene expression arrays. To establish IR injury models, linear accelerator (LINAC) technologies were utilized, and radiation doses optimized. EGCG epithelial effects in these injury models were assessed using light, confocal and electron microscopy, the Griess assay, immunohistochemistry, and gene arrays. SG pretreated with EGCG 7.5 µg/mL promoted epithelial proliferation and the development of pro-acinar buds and ducts in regular homeostasis. Furthermore, EGCG increased the populations of epithelial progenitors in buds and ducts and pro-acinar cells, most probably due to its observed antioxidant activity after IR injury, which prevented epithelial apoptosis. Future studies will assess the potential for nanocarriers to increase the oral bioavailability of EGCG.
| S-EPMC8003734 | biostudies-literature
Project description:Adult hippocampal dentate granule neurons are generated from neural stem cells (NSCs) in the mammalian brain, and the fate specification of adult NSCs is precisely controlled by the local niches and environment, such as the subventricular zone (SVZ), dentate gyrus (DG), and Toll-like receptors (TLRs). Epigallocatechin-3-gallate (EGCG) is the main polyphenolic flavonoid in green tea that has neuroprotective activities, but there is no clear understanding of the role of EGCG in adult neurogenesis in the DG after neuroinflammation. Here, we investigate the effect and the mechanism of EGCG on adult neurogenesis impaired by lipopolysaccharides (LPS). LPS-induced neuroinflammation inhibited adult neurogenesis by suppressing the proliferation and differentiation of neural stem cells in the DG, which was indicated by the decreased number of Bromodeoxyuridine (BrdU)-, Doublecortin (DCX)- and Neuronal Nuclei (NeuN)-positive cells. In addition, microglia were recruited with activatingTLR4-NF-κB signaling in the adult hippocampus by LPS injection. Treating LPS-injured mice with EGCG restored the proliferation and differentiation of NSCs in the DG, which were decreased by LPS, and EGCG treatment also ameliorated the apoptosis of NSCs. Moreover, pro-inflammatory cytokine production induced by LPS was attenuated by EGCG treatment through modulating the TLR4-NF-κB pathway. These results illustrate that EGCG has a beneficial effect on impaired adult neurogenesis caused by LPSinduced neuroinflammation, and it may be applicable as a therapeutic agent against neurodegenerative disorders caused by inflammation.
| S-EPMC4722190 | biostudies-literature
Project description:We have identified Epigallocatechin Gallate (EGCG) as a potent modulator of microglia function. Our aim was to determine whether EGCG affects the transcriptome of microglia and identify genes and gene sets that may underly the effects of EGCG on microglia function.
2024-07-17 | GSE208144 | GEO
Project description:Arterial thrombosis triggers myocardial infarction and is a leading cause of death worldwide. Procoagulant platelets, a subpopulation of activated platelets that expose phosphatidylserine (PS), promote coagulation and occlusive thrombosis. Procoagulant platelets may therefore be a therapeutic target. PS exposure in procoagulant platelets requires TMEM16F, a phospholipid scramblase. Epigallocatechin gallate (EGCG) has been reported to inhibit TMEM16F but this has been challenged. We investigated whether EGCG inhibits PS exposure in procoagulant platelets. PS exposure is often measured using fluorophore-conjugated annexin V. EGCG quenched annexin V-FITC fluorescence, which gives the appearance of inhibition of PS exposure. However, EGCG did not quench annexin V-APC fluorescence. Using this fluorophore, we show that EGCG does not inhibit annexin V binding to procoagulant platelets. We confirmed this by using NBD-labelled PS to monitor PS scrambling. EGCG did not quench NBD fluorescence and did not inhibit PS scrambling. Procoagulant platelets also release PS-exposing extracellular vesicles (EVs) that further propagate coagulation. Surprisingly, EGCG inhibited EV release. This inhibition required the gallate group of EGCG. In conclusion, EGCG does not inhibit PS exposure in procoagulant platelets but does inhibit the EV release. Future investigation of this inhibition may help us further understand how EVs are released by procoagulant platelets.
| S-EPMC8417220 | biostudies-literature