Effects Of Epigallocatechin-3-gallate Research Articles

Gut Microbiota Participates in Polystyrene Microplastics-Induced Hepatic Injuries by Modulating the Gut-Liver Axis.

Dietary pollution by polystyrene microplastics (MPs) can cause hepatic injuries and microbial dysbiosis. Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, exerts beneficial effects on the liver by modulating the gut microbiota. However, the role of microbiota in MPs-induced hepatic injuries and the protective effect of EGCG have not been clarified. Here, 5 μm MPs were orally administered to mice to induce hepatic injuries. Subsequently, antibiotic cocktail (ABX) and fecal microbial transplant (FMT) experiments were performed to investigate the underlying microbial mechanisms. Additionally, EGCG was orally administered to mice to explore its protection against MPs-induced hepatic injuries. Our results showed that MPs activated systemic and hepatic inflammation, promoted fibrosis, and altered the liver metabolome; meanwhile, MPs damaged the gut homeostasis by disturbing the gut microbiome, promoting colonic inflammation, and impairing the intestinal barrier. Notably, MPs reduced the abundance of the probiotics Akkermansia, Mucispirillum, and Faecalibaculum while increasing the pathogenic Tuzzerella. Interestingly, the elimination of gut microbiota mitigated MPs-induced colonic inflammation and intestinal barrier impairment. Moreover, ABX ameliorated MPs-induced systemic and hepatic inflammation but not fibrosis. Correspondingly, microbiota from MPs-administered mice induced colonic, systemic, and hepatic inflammation, while their profibrosis effect on the liver was not observed. Finally, EGCG elevated the abundance of probiotics and effectively repressed MPs-induced colonic inflammation. MPs-induced systemic and hepatic inflammation, fibrosis, and remodeling of the liver metabolome were also attenuated by EGCG. These findings illustrated that gut microbiota contributed to MPs-induced colonic and hepatic injuries, while EGCG could serve as a potential prevention strategy for these adverse consequences.

Biosynthesized Selenium Nanoparticles Using Epigallocatechin Gallate Protect against Pentylenetetrazole-Induced Acute Epileptic Seizures in Mice via Antioxidative, Anti-Inflammatory, and Anti-Apoptotic Activities.

Several negative outcomes are associated with current anti-epileptic medications. Epigallocatechin gallate (EGCG) is a plant-derived compound called catechin and has many medicinal activities, such as anti-inflammatory and antioxidant activities. Biosynthesized selenium nanoparticles are also showing their neuroprotective effect. The anti-epileptic effect of EGCG, alone or with SeNPs, is still debated. Here, we aimed to investigate the potential anti-seizure effect of biosynthesized SeNPs using EGCG (EGCG-SeNPs) against epileptic seizures and hippocampal damage, which is enhanced by pentylenetetrazole (PTZ) injection in mice. Mice were grouped as follows: control; PTZ-exposed group (epileptic model); EGCG + PTZ-treated group; sodium selenite (Na2SeO3) + PTZ-treated group; EGCG-SeNPs + PTZ-treated group; and valproic acid (VPA) + PTZ-treated group. EGCG-SeNPs administration showed anti-epileptic activity by increasing the latency time and reducing the seizure duration following the PTZ injection. Additionally, EGCG-SeNPs counteracted the PTZ-induced changes in oxidants and antioxidants. Moreover, EGCG-SeNPs inhibited the inflammatory response by suppressing the release of pro-inflammatory cytokines and decreasing the immunoreactivity of the glial fibrillary acidic protein and mRNA expression of glutamate receptor subunit zeta-1 (NMDAR; Grin1), showing their inhibitory effect on epilepsy-associated inflammation. Moreover, EGCG-SeNPs reduced PTZ-induced neuronal apoptosis, as indicated by a reduction in the levels of pro-apoptotic proteins and an elevation of the anti-apoptotic protein. Moreover, EGCG-SeNPs administration significantly modulated the PTZ-induced changes in monoamine levels and acetylcholinesterase activity in the hippocampal tissue. The obtained findings suggest the anti-seizure activity of EGCG-SeNPs via their antioxidant, anti-inflammatory, and anti-apoptotic effects, along with their neuromodulatory effect.

Characterization of the Synergistic Antioxidant Activity of Epigallocatechin Gallate (EGCG) and Kaempferol.

Epigallocatechin gallate (EGCG) and kaempferol exhibit cellular antioxidant activity; however, their interactive effects in terms of antioxidant actions and underlying mechanisms remain unclear. In this study, their cytoprotective effects were examined against 2,2-azobis (2-amidinopropane) dihydrochloride solution (ABAP)-induced oxidative stress in HepG2 cells. The results showed that the median effective dose (EC50) of the EGCG and kaempferol (6:1.5, c/c) combination was 3.4 ± 0.1 μg/mL, with a combination index (CIavg) value of 0.54, which represented a significant synergistic effect. Further experiments proved that the combined pretreatment with EGCG and kaempferol exerted protective effects by suppressing reactive oxygen species (ROS) generation, upregulating cellular antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)) in a dose-dependent manner. The mechanism of synergistic antioxidant effects of EGCG combined with kaempferol may be due to the up-regulation of higher antioxidant enzyme activities that improve the antioxidant capacities and balance the cell oxidative stress. The synergistic antioxidant effect of EGCG and kaempferol can provide a theoretical basis for the development of formulas of functional food ingredients.

EGCG, GCG, TFDG, or TSA Inhibiting Melanin Synthesis by Downregulating MC1R Expression

Without affecting cell viability, epigallocatechin gallate (EGCG), gallocatechin gallate (GCG), theaflavine-3,3′-digallate (TFDG), or theasinensin A (TSA) have been found to effectively reduce intracellular melanin content and tyrosinase (TYR) activity. However, studies on the anti-melanogenic mechanism of the above samples remain weak, and the activities of these samples in regulating melanogenesis at the molecular level lack comparison. Using B16F10 cells with the α-melanocyte-stimulating hormone (α-MSH) stimulation and without the α-MSH stimulation as models, the effects of EGCG, GCG, TFDG, or TSA on cell phenotypes and expression of key targets related to melanogenesis were studied. The results showed that α-MSH always promoted melanogenesis with or without adding the four samples. Meanwhile, the anti-melanogenic activities of the four samples were not affected by whether the α-MSH was added in the medium or not and the added time of the α-MSH. On this basis, the 100 µg/mL EGCG, GCG, TFDG, or TSA did not affect the TYR catalytic activity but inhibited melanin formation partly through downregulating the melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), and the TYR family. The downregulation abilities of catechins on the TYR family and MITF expression were stronger than those of dimers at both the transcription and translation levels, while the ability of dimers to downregulate the MC1R expression was stronger than that of catechins at both the transcription and translation levels to some extent. The results of molecular docking showed that these four samples could stably bind to MC1R protein. Taken together, this study offered molecular mechanisms for the anti-melanogenic activity of the EGCG, GCG, TFDG, and TSA, as potential effective components against the UV-induced tanning reactions, and a key target (MC1R) was identified.

Therapeutic Activity of Green Tea Epigallocatechin-3-Gallate on Metabolic Diseases and Non-Alcoholic Fatty Liver Diseases: The Current Updates.

Green tea polyphenols have numerous functions including antioxidation and modulation of various cellular proteins and are thus beneficial against metabolic diseases including obesity, type 2 diabetes, cardiovascular and non-alcoholic fatty liver diseases, and their comorbidities. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea and is attributed to antioxidant and free radical scavenging activities, and the likelihood of targeting multiple metabolic pathways. It has been shown to exhibit anti-obesity, anti-inflammatory, anti-diabetic, anti-arteriosclerotic, and weight-reducing effects in humans. Worldwide, the incidences of metabolic diseases have been escalating across all age groups in modern society. Therefore, EGCG is being increasingly investigated to address the problems. This review presents the current updates on the effects of EGCG on metabolic diseases, and highlights evidence related to its safety. Collectively, this review brings more evidence for therapeutic application and further studies on EGCG and its derivatives to alleviate metabolic diseases and non-alcoholic fatty liver diseases.

Underlying mechanisms and effects of EGCG on the interfacial composition and protein-lipid co-oxidation of whey protein isolate-stabilised O/W emulsions

Addition of different (−)-epigallocatechin-3-gallate (EGCG) (0, 100, 200, 500 or 1000 mg/L emulsion) on the interfacial composition and protein-lipid co-oxidation of whey protein isolate (WPI)-stabilised oil-in-water (O/W) emulsions were studied, and underlying mechanisms were also explored. The results indicated that the physical stability of emulsions gradually decreased with the increasing level of EGCG during storage, which clearly verified by decreasing ζ-potential absolute values and increasing droplet size. Moreover, the combination between WPI and EGCG by covalent/non-covalent binding for either adsorbed proteins (AP) or unadsorbed proteins (UAP) led to aggregation and conformational changes in WPI, which confirmed and characterised by electrophoresis, fluorescence quenching, and molecular docking simulation. Meanwhile, the concentration of AP slightly decreased as a function of EGCG level and storage time, however, the UAP showed the opposite change tendency, indicating that EGCG could effectively modulate the interfacial adsorption property of WPI in O/W emulsions. In addition, the incorporation of EGCG efficiently suppressed protein-lipid co-oxidation of O/W emulsions during storage, which was illustrated by hierarchical cluster and correlation analysis between protein and lipid oxidation products. Our results clearly revealed the viability of the EGCG to modulate the interfacial composition and retard the co-oxidation of O/W emulsions with enhanced storability.

Epigallocatechin-3-gallate Induced HepG2 Cells Apoptosis through ROSmediated AKT /JNK and p53 Signaling Pathway.

Hepatocarcinoma is the third leading cause of cancer-related deaths around the world. Recently, some studies have reported that Epigallocatechin-3-gallate (EGCG) may have the anti-cancer potential. However, the affection and putative mechanisms of cytotoxicity induced by EGCG in HepG2 cells remain unknown. Based on the above, the present study evaluated the effect of EGCG on the cytotoxic and anti-cancer mechanisms of HepG2 cells. The effect of EGCG on the apoptosis of Hep-G2 cells and its mechanism were studied by cell counting kit-8, mitochondrial membrane potential assay with JC-1, Annexin V-FITC apoptosis detection, cell cycle, and apoptosis analysis, one step TUNEL apoptosis assay, caspase 3 activity assay, caspase 9 activity Assay, Reactive Oxygen Species assay, and Western blot. EGCG-induced HepG2 cell apoptosis was confirmed by accumulation of the sub-G1 cells population, translocation of phosphatidylserine, depletion of mitochondrial membrane potential, DNA fragmentation, caspase-3 activation, caspase-9 activation, and poly (ADP-ribose) polymerase cleavage. Furthermore, EGCG enhanced cytotoxic effects on HepG2 cells and triggered intracellular reactive oxygen species; the signaling pathways of AKT, JNK, and p53 were activated to advance cell apoptosis. The results reveal that EGCG may provide useful information on EGCG-induced HepG2 cell apoptosis and be an appropriate candidate for cancer chemotherapy.

The Potential Role of Epigallocatechin-3-Gallate (EGCG) in Breast Cancer Treatment

Breast cancer is one of the most diagnosed cancers worldwide, with an incidence of 47.8%. Its treatment includes surgery, radiotherapy, chemotherapy, and antibodies giving a mortality of 13.6%. Breast tumor development is driven by a variety of signaling pathways with high heterogeneity of surface receptors, which makes treatment difficult. Epigallocatechin-3-gallate (EGCG) is a natural polyphenol isolated as the main component in green tea; it has shown multiple beneficial effects in breast cancer, controlling proliferation, invasion, apoptosis, inflammation, and demethylation of DNA. These properties were proved in vitro and in vivo together with synergistic effects in combination with traditional chemotherapy, increasing the effectiveness of the treatment. This review focuses on the effects of EGCG on the functional capabilities acquired by breast tumor cells during its multistep development, the molecular and signal pathways involved, the synergistic effects in combination with current drugs, and how nanomaterials can improve its bioavailability on breast cancer treatment.

Effects of epigallocatechin gallate, caffeine, and their combination on fat accumulation in high-glucose diet-fed Caenorhabditis elegans.

Epigallocatechin gallate (EGCG) and caffeine are inevitable to be ingested together in the process of drinking green tea. This study used Caenorhabditis elegans as an organism model to examine whether the binding of EGCG and caffeine could influence the fat-reduction effect. The results revealed that EGCG significantly reduced the Nile Red fluorescence intensity and the triglyceride/protein ratio of the C. elegans obesity model by 14.7% and 16.5%, respectively, while the effect of caffeine was not significant. Moreover, the degree of reduction in fluorescence intensity and triglyceride/protein ratio by EGCG+caffeine was comparable to that of EGCG. In the exploration of underlying mechanism, we found that EGCG and EGCG+caffeine treatments had no influence on food intake and energy expenditure of C. elegans. Their fat-reduction effects were dependent on the regulation of lipogenesis, as shown by the decreased expression of the sbp-1, fat-7, and daf-16 genes.

Influence of Epigallocatechin Gallate on Quality of Cooked Harpiosquillid Mantis Shrimp (Harpiosquilla raphidea) Subjected to Multiple Freeze-Thaw Cycles

Effects of epigallocatechin gallate (EGCG) at 200 or 400 ppm on quality changes of cooked Harpiosquillid mantis shrimp (Harpiosquilla raphidea) (CHMS) meat subjected to varying freeze-thaw cycles (F-T-C; 0, 1, 3, and 5) were studied. With augmenting F-T-C, the CHMS meat underwent deterioration to higher extent as indicated by upsurges in exudate loss, tougher texture along with increased microbial counts. The addition of EGCG could retard those changes in a dose-dependent manner. Furthermore, EGCG prevented microbial growth as ascertained by lower counts and total volatile basic nitrogen (TVB) content. Lipid oxidation was also impeded in the presence of EGCG, especially at a high concentration as evidenced by lowered malondialdehyde (MDA), while maintaining polyunsaturated fatty acids, particularly EPA and DHA when F-T-C raised. Total disulfide bond content and surface hydrophobicity of CHMS added with EGCG were lower than those of the control. Those alterations were more retarded as EGCG concentration increased. Therefore EGCG at 400 ppm effectively prevented quality loss of CHMS meat during repeated F-T process.

P-631 Alleviating effects of EGCG on ovarian hyperstimulation syndrome and the potential modulating mechanism through the VEGF pathway

Abstract Study question What are the underlying mechanisms of EGCG to alleviate Ovary hyperstimulation syndrome (OHSS)? Summary answer EGCG inhibited VEGF via TGF-β1 classical-SMAD pathway and 67LR-mediated CREB pathway and could reduce the ovarian inflammatory effect and attenuated OHSS progress in rat model. What is known already Ovarian hyperstimulation syndrome (OHSS) is one of the most severe complications of COH during IVF treatment. The pathophysiology of OHSS is characterized by increased capillary permeability, VEGF is an important mediator in OHSS, and serum VEGF levels have been shown to correlate with OHSS severity. (-)-epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active polyphenolic catechin in green tea and has been reported to have multiple effects in humans. Many research indicated that in many pathological processes, EGCG could inhibit VEGF and its receptor expression and have an angiogenesis effect. Herein, EGCG might have a therapeutic effect on OHSS. Study design, size, duration We investigated the role of EGCG in OHSS in vitro and in vivo. The primary human granulosa-lutein(hGL) cells and human granulosa-like tumor (KGN) cell line were cultured and treated with different concentrations of EGCG for 24 hours. Animal OHSS model was established in SD rats by injection of pregnant mare serum gonadotropin (PMSG), and randomly assigned to receive vehicle only or EGCG for 3 days. All experiments were performed 3-8 times for comparisons. Participants/materials, setting, methods The effect of EGCG on KGN and hGL cells was determined by MTT assay. The body weight of rats was measured every day, and the ovary size was measured after removal, the permeability was determined by Evans-blue. The serum estrogen and VEGF level in rats were detected by ELISA. RNA and protein expressions of VEGF, VEGFR-2, TGF-β, and TβR II were detected by qPCR and Western-blotting and immunostaining in vitro and in vivo experiments. Main results and the role of chance Our study demonstrated that administration of EGCG attenuated the development of OHSS in rats, as shown by histological examination and ovarian weight and morphology. The ovary weight was significantly decreased in the EGCG treatment group compared with the OHSS group (147.9 vs 206.5 mg). Additionally, compared to OHSS rats, EGCG treated rats exhibit downregulated ovarian VEGF expression determined by IHC and RT-qPCR. VEGF and E2 protein levels significantly decrease in the serum of the EGCG treatment group. EGCG exerted inhibitory effects on cell growth only in high dose (50uM) and longtime (48h) treatment in KGN and hGL cells. In KGN cells and hGL cells, EGCG significantly reduces the expression of VEGF and TGF-β at the RNA and protein levels. Furthermore, EGCG inhibits TGF-β1-induced VEGF production and secretion in KGN cells by suppressing TGF-β expression and its traditional Smad signaling pathway. EGCG also downregulates VEGF expression through the 67-kDa laminin receptor-mediated PKA-CREB pathway. Limitations, reasons for caution EGCG has been reported to employ a wide range of biological effects. Therefore, its suppressive effects on VEGF and TGF-β signaling pathway might be part of the pharmacological mechanisms to alleviate Ovary hyperstimulation syndrome. Further studies are also needed to explore the therapeutic mechanisms of melatonin from other perspectives. Wider implications of the findings Our findings add mechanistic insight in support of using EGCG as an adjuvant therapy in the management of OHSS. EGCG shows the potential to act as a novel alternative therapeutic drug to treat OHSS. Daily intake of green tea might be beneficial for women under COH to prevent OHSS. Trial registration number Not applicable

Hormetic effects of EGC and EGCG on CES1 activity and its rescue from oxidative stress in rat liver S9

Carboxylesterase 1 (CES1) is a hydrolytic enzyme that plays an important role in the activation or deactivation of many therapeutic agents, thus affecting their pharmacokinetic and pharmacodynamic outcomes. Using rat liver S9 as an enzyme source and enalapril as a CES1 substrate, the present study examined effects of a number of flavonoids on the formation of enalaprilat (the active form of enalapril) produced by CES1-mediated hydrolysis. While a majority of flavonoids tested showed inhibition on CES1, an unexpected hormetic effect was observed for epigallocatechin (EGC) and epigallocatechin gallate (EGCG), i.e., stimulatory effect at low concentrations and enzyme inhibition at high concentrations. Further experiments revealed that oxidative stress caused by hydrogen peroxide, arachidonic acid plus iron, and oxidized low density lipoproteins (oxLOL) reduced CES1 activity in rat liver S9 and the loss of CES1 enzyme activity could be rescued largely by EGC or EGCG. In contrast, such effects were minimal in human liver S9, probably due to the presence of a higher ratio of reduced vs oxidized forms of glutathione. The above findings suggest that the polyphenolic nature of EGC or EGCG might be responsible for rescuing CES1 activity under oxidative stress. Because of the importance of CES1 in drug activation or deactivation and rat liver S9 as a versatile in vitro system used for drug metabolism studies and drug safety assessment, caution should be exercised to avoid potential biases for data interpretation and decision making when CES1 activity in rat liver S9 is evaluated with dependency on experimental conditions.

Autophagy or Apoptosis: Anticancer Molecular Mechanism of Epigallocatechin Gallate with Natural Polyphenol Effect on HepG2 Cells Viability

Background: The anticancer impact of Epigallocatechin gallate (EGCG) the highly active polyphenol of green tea was abundantly studied. Though, the exact mechanism of its cytotoxicity is still under investigation. Objectives: Hence, the current study designed to investigate the molecular target of EGCG in HepG2 cells on thirteen autophagy- and/or apoptosis- related genes. Methods: The apoptosis detection analyses such as flow cytometry and dual apoptosis assay were used. The genes expression profile was explored by the real-time quantitative-PCR. Results: EGCG increases G0/G1 cell cycle arrest and the real-time apoptosis markers proteins leading to stimulate apoptosis in 70% of the treated HepG2 cells. The up-regulation was recorded in two of autophagy inhibitory genes (FOS-1, FOS-2) and apoptosis inducer gene (DDIT3). While the other ten genes expressed down-regulation after treatment. The down regulation was manifested in the genes of mitochondrial autophagy marker proteins (BNIP3, BNIP3L, and NBR1), the autophagy regulator genes (BIRC5, MAPK9), and the gene that implicated in protein biosynthesis and protein modification (ITGB1). The genes that have pro-apoptotic function in cells (CAPNS1, CFLAR, EIF4G, and RB1) were also showed down-regulation after treatment. Conclusion: Thus, the results demonstrated a potential effect of EGCG to induce apoptosis rather than autophagy in the treated HepG2 cells that could play a good target for therapy.

Mechanisms Underlying the Effects of the Green Tea Polyphenol EGCG in Sarcopenia Prevention and Management.

Sarcopenia is prevalent among the older population and severely affects human health. Tea catechins may benefit for skeletal muscle performance and protect against secondary sarcopenia. However, the mechanisms underlying their antisarcopenic effect are still not fully understood. Despite initial successes in animal and early clinical trials regarding the safety and efficacy of (-)-epigallocatechin-3-gallate (EGCG), a major catechin of green tea, many challenges, problems, and unanswered questions remain. In this comprehensive review, we discuss the potential role and underlying mechanisms of EGCG in sarcopenia prevention and management. We thoroughly review the general biological activities and general effects of EGCG on skeletal muscle performance, EGCG's antisarcopenic mechanisms, and recent clinical evidence of the aforesaid effects and mechanisms. We also address safety issues and provide directions for future studies. The possible concerted actions of EGCG indicate the need for further studies on sarcopenia prevention and management in humans.

Molecular mechanisms underlying the epigallocatechin-3-gallate-mediated inhibition of oral squamous cell carcinogenesis

ObjectivesTo reveal the mechanisms underlying the epigallocatechin-3-gallate (EGCG)-mediated inhibition of carcinogenesis and the related regulatory signaling pathways. DesignThe effect of EGCG on the proliferation of OSCC cells was examined. SuperPred, ChEMBL, Swiss TargetPrediction, DisGeNET, GeneCards, and National Center for Biotechnology Information databases were used to predict the EGCG target genes and oral leukoplakia (OL)-related, oral submucosal fibrosis (OSF)-related, and OSCC-related genes. The binding of EGCG to the target proteins was simulated using AutoDock and PyMOL. The Cancer Genome Atlas (TCGA) dataset was subjected to consensus clustering analysis to predict the downstream molecules associated with these targets, as well as their potential functions and pathways. ResultsEGCG significantly inhibited OSCC cell proliferation (p < 0.001). By comparing EGCG target genes with genes linked to oral potentially malignant disorder (OPMD) and OSCC, a total of eleven potential EGCG target genes were identified. Furthermore, EGCG has the capacity to bind to eleven proteins. Based on consensus clustering and enrichment analysis, it is suggested that EGCG may hinder the progression of cancer by altering the cell cycle and invasive properties in precancerous lesions of the oral cavity. Some possible strategies for modifying the cell cycle and invasive properties may include EGCG-mediated suppression of specific genes and proteins, which are associated with cancer development. ConclusionsThis study investigated the molecular mechanisms and signaling pathways associated with the EGCG-induced suppression of OSCC. The identification of specific pharmacological targets of EGCG during carcinogenesis is crucial for the development of innovative combination therapies involving EGCG.

A green tea extract catechin EGCg: Therapeutic potential for pediatric cardiomyopathies

AbstractCardiomyopathies comprise a group of disorders wherein the primary defect is in cardiac myocytes. The common forms of pediatric cardiomyopathies, classified according to their morphological and functional manifestations, include dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), hypertrophic cardiomyopathy (HCM), and others. Cardiac gene mutations caused abnormal myofibril Ca2+ sensitivity may be involved in the underlying molecular mechanisms of cardiomyopathies. Thus far, no effective treatment for cardiomyopathies has been developed, especially for HCM and RCM in which diastolic dysfunction occurs early and followed by diastolic heart failure. Our laboratory is among the first in the field to investigate the mechanisms underlying various cardiomyopathies and search for the treatment for these disorders. In the past, we and other researchers have found that (−)‐epigallocatechin‐3‐gallate (EGCg), the major biomedical polyphenol extracted from green tea, possess multiple therapeutic effects on protecting cardiac function and correcting impaired relaxation. Given its therapeutic effects, EGCg might be a potential drug candidate for administration to patients with cardiomyopathy and heart failure. In this review, we will discuss the molecular mechanisms associated with the pathogenesis of diastolic dysfunction and summarize the pharmacological effects of EGCg on experimental animals and pediatric patients with cardiomyopathies and diastolic dysfunction.

Suppression of the excitability of rat nociceptive secondary sensory neurons following local administration of the Phytochemical, (-)-Epigallocatechin-3-gallate

The phytochemical, polyphenolic compound, (-)-epigallocatechin-3-gallate (EGCG), is the main catechin found in green tea. Although a modulatory effect of EGCG on voltage-gated sodium and potassium channels has been reported in excitable tissues, the in vivo effect of EGCG on the excitability of nociceptive sensory neurons remains to be determined. Our aim was to investigate whether local administration of EGCG to rats attenuates the excitability of nociceptive spinal trigeminal nucleus caudalis (SpVc) neurons in response to mechanical stimulation in vivo. Extracellular single unit recordings were made from SpVc neurons in response to orofacial mechanical stimulation of anesthetized rats. The mean firing frequency of SpVc wide-dynamic range neurons following both non-noxious and noxious mechanical stimuli was significantly inhibited by EGCG in a dose-dependent and reversible manner. The mean magnitude of inhibition by EGCG on SpVc neuronal discharge frequency was similar to that of the local anesthetic, 1% lidocaine. Local injection of half-dose of lidocaine replaced the half-dose of EGCG. These results suggest that local injection of EGCG suppresses the excitability of nociceptive SpVc neurons, possibly via the inhibition of voltage-gated sodium channels and opening of voltage-gated potassium channels in the trigeminal ganglion. Therefore, administration of EGCG as a local anesthetic may provide relief from trigeminal nociceptive pain without side effects.

Epigallocatechin gallate (EGCG) inhibits lipopolysaccharide-induced inflammation in RAW 264.7 macrophage cells via modulating nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) signaling pathway.

Epigallocatechin-3-gallate (EGCG) is a major bioactive compound in tea polyphenol extract. After ingestion, EGCG reaches the intestine and may commence anti-inflammation in the intestinal organ. Thus, in this paper, the anti-inflammatory effect of EGCG was studied using lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells. LPS induction instigated morphological deformation extensively which was normalized by EGCG. In LPS-induced macrophage cells, EGCG was found to lower cellular nitric oxide (32% of LPS group) and intercellular ROS level (45.4% of LPS group). It also suppressed the expression of IL-1β (LPS 132.6 ± 14.6, EGCG 10.67 ± 3.65), IL-6 (LPS 2994.44 ± 178.5, EGCG 408.33 ± 52.34), TNF-α (LPS 27.11 ± 2.84, EGCG 1.22 ± 0.03), and iNOS (LPS 40.45 ± 11.17, EGCG 10.24 ± 0.89). The GO function analysis identified that these differential genes involved 24 biological processes, 18 molecular functions, and 19 cellular component-related processes. KEGG pathway enrichment analysis revealed that LPS significantly affects NF-κB, TNF, and TLR signaling pathways. Western blotting revealed that EGCG diminished P-IκB/IκB ratio by 75% and p-p65/p65 by 50% compared to the LPS group. Finally, Arg-1 and CD-206 mRNA expression were determined by RT-PCR, which was consistent with the RNA-Seq result. These findings indicate that EGCG exerts an anti-inflammatory effect by reducing NO and ROS production, suppressing TLR4 protein expression, and inhibiting IκB and p65 phosphorylation.

Targeting fibrotic signaling pathways by EGCG as a therapeutic strategy for uterine fibroids

Fibrosis is characterized by excessive accumulation of extracellular matrix, which is a key feature of uterine fibroids. Our prior research supports the tenet that inhibition of fibrotic processes may restrict fibroid growth. Epigallocatechin gallate (EGCG), a green tea compound with powerful antioxidant properties, is an investigational drug for uterine fibroids. An early phase clinical trial showed that EGCG was effective in reducing fibroid size and its associated symptoms; however, its mechanism of action(s) has not been completely elucidated. Here, we probed effects of EGCG on key signaling pathways involved in fibroid cell fibrosis. Viability of myometrial and fibroid cells was not greatly affected by EGCG treatment (1–200 µM). Cyclin D1, a protein involved in cell cycle progression, was increased in fibroid cells and was significantly reduced by EGCG. EGCG treatment significantly reduced mRNA or protein levels of key fibrotic proteins, including fibronectin (FN1), collagen (COL1A1), plasminogen activator inhibitor-1 (PAI-1), connective tissue growth factor (CTGF), and actin alpha 2, smooth muscle (ACTA2) in fibroid cells, suggesting antifibrotic effects. EGCG treatment altered the activation of YAP, β-catenin, JNK and AKT, but not Smad 2/3 signaling pathways involved in mediating fibrotic process. Finally, we conducted a comparative study to evaluate the ability of EGCG to regulate fibrosis with synthetic inhibitors. We observed that EGCG displayed greater efficacy than ICG-001 (β-catenin), SP600125 (JNK) and MK-2206 (AKT) inhibitors, and its effects were equivalent to verteporfin (YAP) or SB525334 (Smad) for regulating expression of key fibrotic mediators. These data indicate that EGCG exhibits anti-fibrotic effects in fibroid cells. These results provide insight into mechanisms behind the observed clinical efficacy of EGCG against uterine fibroids.

The Potential of Epigallocatechin-3-gallate (EGCG) as Complementary Medicine for the Treatment of Inflammatory Bowel Disease.

Complementary and alternative medicine has the potential to enrich conventional therapy to improve the treatment of various diseases. Patients that suffer from inflammatory bowel disease, which requires a constant need for medication, have to deal with the adverse effects of repeated application. Natural products such as Epigallocatechin-3-gallate (EGCG) possess the potential to improve symptoms of inflammatory diseases. We investigated the efficacy of EGCG on an inflamed co-culture model simulating IBD and compared it to the efficacies of four commonly applied active pharmaceutical ingredients. EGCG (200 µg/mL) strongly stabilized the TEER value of the inflamed epithelial barrier to 165.7 ± 4.6% after 4 h. Moreover, the full barrier integrity was maintained even after 48 h. This corresponds to the immunosuppressant 6-Mercaptopurin and the biological drug Infliximab. The EGCG treatment significantly decreased the release of the pro-inflammatory cytokines IL-6 (to 0%) and IL-8 (to 14.2%), similar to the effect of the corticosteroid Prednisolone. Therefore, EGCG has a high potential to be deployed as complementary medicine in IBD. In future studies, the improvement of EGCG stability is a key factor in increasing the bioavailability in vivo and fully harnessing the health-improving effects of EGCG.