Tea Polyphenol Epigallocatechin Gallate Research Articles

Epigallocatechin gallate regulates the myeloid-specific transcription factor PU.1 in macrophages.

Our previous research demonstrated that PU.1 regulates expression of the genes involved in inflammation in macrophages. Selective knockdown of PU.1 in macrophages ameliorated LPS-induced acute lung injury (ALI) in bone marrow chimera mice. Inhibitors that block the transcriptional activity of PU.1 in macrophages have the potential to mitigate the pathophysiology of LPS-induced ALI. However, complete inactivation of PU.1 gene disrupts normal myelopoiesis. Although the green tea polyphenol Epigallocatechin gallate (EGCG) has been shown to regulate inflammatory genes in various cell types, it is not known if EGCG alters the transcriptional activity of PU.1 protein. Using Schrodinger Glide docking, we have identified that EGCG binds with PU.1 protein, altering its DNA-binding and self-dimerization activity. In silico analysis shows that EGCG forms Hydrogen bonds with Glutamic Acid 209, Leucine 250 in DNA binding and Lysine 196, Tryptophan 193, and Leucine 182 in the self-dimerization domain of the PU.1 protein. Experimental validation using mouse bone marrow-derived macrophages (BMDM) confirmed that EGCG inhibits both DNA binding by PU.1 and self-dimerization. Importantly, EGCG had no impact on expression of the total PU.1 protein levels but significantly reduced expression of various inflammatory genes and generation of ROS. In summary, we report that EGCG acts as an inhibitor of the PU.1 transcription factor in macrophages.

Organic Exfoliation of Hydrophilic Bentonite using Aliquat 336 and Isobutyl(Trimethoxy)Silane to Enhance its Activity Toward pH-Dependent Adsorption of Epigallocatechin Gallate

AbstractThe most potent and significant polyphenolic molecule from tea catechins is epigallocatechin gallate (EGCG); it has potential anti-cancer and anti-inflammatory properties. Methods are needed to mitigate its presence in the environment and protect humans from exposure. The objective of the present study was to investigate a functionalized, low-cost clay mineral as an adsorbent for the tea polyphenol EGCG. Hydrophilic bentonite (Bn) was functionalized using Aliquat 336 (A336) and isobutyl(trimethoxy)silane (IBTS). The degree of clay functionalization depended on the extent of introduction of alkyl linkages between the superimposed clay layers. Results revealed that Aliquat 336 functionalized clay (A336-Bn) exhibited maximum thermal stability at 500°C and it is a promising adsorbent for ECGC with a maximum adsorption capacity of 196.26 mg/g at equilibrium. Experimental data were analyzed using pseudo-first order and pseudo-second order models. Adsorption isotherms were interpreted from the Freundlich adsorption isotherm.

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.

Tea polyphenol EGCG ameliorates obesity-related complications by regulating lipidomic pathway in leptin receptor knockout rats

Tea polyphenol epigallocatechin-3-gallate (EGCG) has been widely recognized for antiobesity effects. However, the molecular mechanism of lipidomic pathway related to lipid-lowering effect of EGCG is still not well understood. The aim of this study was to investigate the effects and mechanism of EGCG activated hepatic lipidomic pathways on ameliorating obesity-related complications by using newly developed leptin receptor knockout (Lepr KO) rats. Results showed that EGCG supplementation (100 mg/kg body weight) significantly decreased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels both in the serum and liver, and significantly improved glucose intolerance. In addition, EGCG alleviated fatty liver development and restored the normal liver function in Lepr KO rats. Liver lipidomic analysis revealed that EGCG dramatically changes overall composition of lipid classes. Notably, EGCG significantly decreased an array of triglycerides (TGs) and diglycerides (DGs) levels. While EGCG increased 31 glycerophospholipid species and one sphingolipid species levels, such as phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), phosphatidylserines (PSs) and phosphatidylinositols (PIs) levels in the liver of Lepr KO rats. Moreover, 14 diversely regulated lipid species were identified as potential lipid biomarkers. Mechanistic analysis revealed that EGCG significantly activated the SIRT6/AMPK/SREBP1/FAS pathway to decrease DGs and TGs levels and upregulated glycerophospholipids synthesis pathways to increase glycerophospholipid level in the liver of Lepr KO rats. These findings suggested that the regulation of glycerolipids and glycerophospholipid homeostasis might be the key pathways for EGCG in ameliorating obesity-related complications in Lepr KO rats.

Green tea polyphenol EGCG acts differentially on the end stage aggregated polymorphs of α-synuclein generated in the presence of polyol osmolytes.

Synucleinopathies such as Parkinson's disease, multiple systems atrophy, and dementia with Lewy bodies, are characterized by the presence of α-synuclein (α-syn) aggregates. Recently, it was found that different variants of synucleinopathies are encoded by biochemically diverse aggregated polymorphs of α-syn referred to as ‘strains’. Precise structural information on the α-syn pathological aggregates is one of the few knowledge gaps that encumber the design of effective therapies against synucleinopathies. Natural polyphenolic compounds such as epigallocatechin gallate (EGCG) have shown their efficacies in inhibiting the aggregation, as well as in remodelling of preformed aggregates of α-syn. However, a comparative account of EGCG's effect on different polymorphs of α-syn aggregates is not well explored. In this work, diverse aggregated polymorphs of α-syn were generated in the presence of different polyol osmolytes used as small-molecule crowding agents. The polymorphic aggregates of α-syn thus generated were treated with EGCG and the end products were analyzed structurally. The structural distinction of these polymorphs was assessed using FTIR, CD, AFM and proteinase K digestion. We observed that EGCG differentially acts upon all the polymorphs wherein EGCG incubated species were either disintegrated or structurally altered. Interestingly, contrary to previous reports, the EGCG treated polymorphs were β-sheet rich. Our findings are relevant in assessing the efficacy of polyphenolic compounds on diverse aggregated strains of different proteins that are shown to encode different disease variants. The appearance of β-sheet rich species in this study also engenders a more detailed examination of EGCG's mode of action on diverse classes of amyloids.

Exploring the Absorption Mechanisms of Imidazolium-Based Ionic Liquids to Epigallocatechin Gallate.

Imidazolium-based ionic liquids are wildly used in natural product adsorption and purification. In this work, one typical polymeric ionic liquid (PIL) was synthesized by using L-proline as the anion, which exhibited excellent adsorption capacity toward tea polyphenol epigallocatechin gallate (EGCG). The adsorption conditions were optimized with the response surface method (RSM). Under the optimum conditions, the adsorption capacity of the PIL for EGCG can reach as high as 552 mg/g. Dynamics and isothermal research shows that the adsorption process of EGCG by the PIL particularly meets the quasi-second-order kinetic equation and monolayer adsorption mechanism. According to thermodynamic parameter analysis, the adsorption process is endothermic and spontaneous. The results of theoretical calculation by molecular docking also demonstrated the interaction mechanisms between EGCG and the ionic liquid. Considering the wide application of imidazolium-based ionic liquids in component adsorption and purification, the present study can not only be extended to other similar experimental mechanism validation, but also be representative for guiding the synthesis of PIL and optimization of adsorption conditions.

EGCG has Dual and Opposing Effects on the N-terminal Region of Self-associating α-synuclein Oligomers

Oligomers of the protein α-synuclein (α-syn) are thought to be a major toxic species in Parkinson’s disease, particularly through their ability to permeabilize cell membranes. The green tea polyphenol epigallocatechin gallate (EGCG) has been found to reduce this ability. We have analyzed α-syn oligomer dynamics and interconversion by H/D exchange monitored by mass spectrometry (HDX-MS). Our results show that the two oligomers OI and OII co-exist in equilibrium; OI is a multimer of OII and its dissociation can be followed by HDX-MS by virtue of the correlated exchange of the N-terminal region. Urea destabilizes the α-syn oligomers, dissociating OI to OII and monomers. Oligomers exposed to EGCG undergo Met oxidation. Intriguingly, EGCG induces an oxidation-dependent effect on the structure of the N-terminal region. For the non-oxidized N-terminal region, EGCG increases the stability of the folded structure as measured by a higher level of protection against H/D exchange. In contrast, protection is clearly abrogated in the Met oxidized N-terminal region. Having a non-oxidized and disordered N-terminal region is known to be essential for efficient membrane binding. Therefore, our results suggest that the combined effect of a structural stabilization of the non-oxidized N-terminal region and the presence of a disordered oxidized N-terminal region renders the oligomers less cytotoxic by decreasing the ability of the N-terminal region to bind to cell membranes and facilitate their permeabilization.

Metabolomics and proteomics analyses revealed mechanistic insights on the antimicrobial activity of epigallocatechin gallate against Streptococcus suis.

Streptococcus suis (S. suis) is a highly virulent zoonotic pathogen and causes severe economic losses to the swine industry worldwide. Public health security is also threatened by the rapidly growing antimicrobial resistance in S. suis. Therefore, there is an urgent need to develop new and safe antibacterial alternatives against S. suis. The green tea polyphenol epigallocatechin gallate (EGCG) with a number of potential health benefits is known for its antibacterial effect; however, the mechanism of its bactericidal action remains unclear. In the present, EGCG at minimal inhibitory concentration (MIC) showed significant inhibitory effects on S. suis growth, hemolytic activity, and biofilm formation, and caused damage to S. suis cells in vitro. EGCG also reduced S. suis pathogenicity in Galleria mellonella larvae in vivo. Metabolomics and proteomics analyses were performed to investigate the underlying mechanism of antibacterial activity of EGCG at MIC. Many differentially expressed proteins involved in DNA replication, synthesis of cell wall, and cell membrane, and virulence were down-regulated after the treatment of S. suis with EGCG. EGCG not only significantly reduced the hemolytic activity of S. suis but also down-regulated the expression of suilysin (Sly). The top three shared KEGG pathways between metabolomics and proteomics analysis were ABC transporters, glycolysis/gluconeogenesis, and aminoacyl-tRNA biosynthesis. Taken together, these data suggest that EGCG could be a potential phytochemical compound for treating S. suis infection.

Higher affinity of polyphenol to zein than to amyloid fibrils leading to nanoparticle-embed network wall scaffold to construct amyloid fibril-zein-EGCG hydrogels for coating of beef

Globally, 800 million are undernourished and 2 billion are deficient in micronutrients. A regular dietary intake of meat is one of effective strategies to fight against undernourishment and deficiency of micronutrients. However, meat is a typical perishable food; proper handling to extend the shelf life of meat is required. In the present study, homogenous hydrogels composed with high contents of lysozyme amyloid fibrils, zein and green tea polyphenol epigallocatechin gallate (EGCG) were developed via the orchestration of protein–protein interaction and polyphenol-protein interaction for coating of beef. The protein–protein interaction between amyloid fibrils and zein showed higher affinity than that of the polyphenol-protein interactions. In addition, polyphenol EGCG was found to be more inclined to bind with zein than to the amyloid fibrils. Thus, the amyloid fibrils performed as the scaffold, in which EGCG on one hand induced the zein aggregate nanoparticles and on the other hand deposited on the surface of amyloid fibrils, leading to the dense multi-pore network with the nanoparticle-embed wall. It served as the microstructure mechanism for the enhanced gel strength. Coating of fresh chilling beef with the amyloid fibril-zein-EGCG hybrid hydrogels effectively protected the freshness and tenderness through inhibiting the over-growth of microorganisms and oxidation of lipid. This study paves the way to develop functional edible biomaterials via polyphenol induced coordination of the protein–protein interaction and polyphenol-protein interaction, where polyphenol acts as the molecular glue. This strategy shows high application potentials in health promotion related fields, including edible coating to extend the shelf-life of fresh meat.

Painful Diabetic Neuropathy Is Associated with Compromised Microglial IGF-1 Signaling Which Can Be Rescued by Green Tea Polyphenol EGCG in Mice.

Background Painful diabetic neuropathy (PDN) is a frequent and troublesome complication of diabetes, with little effective treatment. PDN is characterized by specific spinal microglia-mediated neuroinflammation. Insulin-like growth factor 1 (IGF-1) primarily derives from microglia in the brain and serves a vital role in averting the microglial transition into the proinflammatory M1 phenotype. Given that epigallocatechin-3-gallate (EGCG) is a potent anti-inflammatory agent that can regulate IGF-1 signaling, we speculated that EGCG administration might reduce spinal microglia-related neuroinflammation and combat the development of PDN through IGF-1/IGF1R signaling. Methods Type 1 diabetes mellitus (T1DM) was established by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) in mice. The protein expression level of IGF-1, its receptor IGF1R, interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) was determined by Western blot or immunofluorescence. Results The spinal IGF-1 expression markedly decreased along with the presence of pain-like behaviors, the spinal genesis of neuroinflammation (increased IL-1β, TNF-α, and Iba-1+ microglia), and the intensified M1 microglia polarization (increased iNOS+Iba-1+ microglia) in diabetic mice. IGF-1 could colocalize with neurons, astrocytes, and microglia, but only microglial IGF-1 was repressed in T1DM mice. Furthermore, we found that i.t. administration of mouse recombinant IGF-1 (rIGF-1) as well as i.t. or i.p. treatment with EGCG alleviated the diabetes-induced pain-like behaviors, reduced neuroinflammation (suppressed IL-1β, TNF-α, and Iba-1+ microglia), prevented the M1 microglia polarization (less iNOS+Iba-1+ microglia), and restored the microglial IGF-1 expression. Conclusions Our data highlighted the importance of maintaining spinal IGF-1 signaling in treating microglia-related neuroinflammation in PDN. This study also provides novel insights into the neuroprotective mechanisms of EGCG against neuropathic pain and neuroinflammation through IGF-1 signaling, indicating that this agent may be a promising treatment for PDN in the clinical setting.

High Internal Phase Emulsions Stabilized with Polyphenol-Amyloid Fibril Supramolecules for Encapsulation and Protection of Lutein.

High internal phase emulsions (HIPEs), also called highly concentrated emulsions with a minimal internal phase volume fraction of 74%, have been paid increasing attention in the development of functional foods due to their high potential in loading with large amounts of hydrophobic nutriceuticals. In the present study, HIPEs stabilized by polyphenol-amyloid supramolecular filaments were prepared for encapsulation of olive oil and loading with lutein. Binding and stacking of the green tea polyphenol epigallocatechin gallate (EGCG) on the surface of amyloid fibrils fabricated from hen egg lysozyme resulted in the hybrid supramolecules, which assembled to form hydrogels. The amyloid fibril clusters shrouded by EGCG were observed in the microstructure of the hydrogels characterized by atomic force microscopy (AFM). HIPEs stabilized by the EGCG-amyloid fibril supramolecules showed the typical microstructure of highly packed polyhedral geometric oil droplets. The gel strength of the HIPEs stabilized by the hybrid supramolecules was greater than that of HIPEs stabilized by pure amyloid fibrils. The droplet size of the HIPEs first decreased and then increased with the increase of EGCG contents in the hybrid supramolecules, which was consistent with the corresponding emulsion morphologies obtained from the images of confocal laser scanning microscopy (CLSM). Aggregation of the protein-based nanofibrils appeared in the continuous phase at higher EGCG contents. The droplet size of the HIPEs decreased with the increase of the amyloid fibril concentration, accompanied by more packed and homogenously dispersed lipid droplets, as shown in the CLSM images. A high loading content of lutein of up to 10 mg/mL in the prepared HIPEs was realized, and the stability of lutein against ultraviolet irradiation, heat, iron, and hydrogen peroxide was promoted significantly. In addition, encapsulation with the HIPEs prevented the oxidization of olive oil, and this effect was enhanced with the increase of the EGCG content in the hybrid supramolecules ranging from 0 to 0.25 wt %. The protection function of the HIPEs might be ascribed to the membrane of interfacial amyloid fibrils and the crowded oil droplet environment, both of which could shield the pro-oxidation factors.

An unconventional nano-AIEgen originating from a natural plant polyphenol for multicolor bioimaging

Biocompatible aggregation-induced emission (AIE) materials from natural resources are of great interest for a variety of potential applications. Here, we report the unconventional AIE nature of the green tea polyphenol epigallocatechin gallate (EGCG), which is investigated by observing the disappearance and reoccurrence of fluorescence when EGCG is dissolved and recrystallized in aqueous solutions. The intermolecular through-space conjugation and structural rigidification induced by multiple intermolecular H-bonds play critical roles in the AIE phenomenon. This inspires the development of a multicolored, monodisperse, photostable, and non-toxic nano-AIE luminogen (nano-AIEgen), which is simply prepared by polyphenol-amine-based crosslinking in aqueous solutions, demonstrating great potential for living cell bioimaging. Our strategy to develop nano-AIEgens using AIE-active hydrophilic natural products—e.g., plant polyphenols, such as tannic acid, that exhibit similar AIE characteristics—can help push the boundary of the exploration of various novel, large-scale, biocompatible, water-soluble, and degradable AIE materials from natural resources. • AIE phenomenon for EGCG in the solid state • The AIE activity results from through-space conjugation by intermolecular H-bonds • The EGCG nano-AIEgens may be successfully used to image living cells As a plant polyphenol, epigallocatechin gallate is highly soluble in water and non-toxic. Here, Lu et al. demonstrate an interesting AIE phenomenon in common natural products and propose strategies for screening and developing hydrophilic AIEgens from natural products.

Research progress of EGCG in the treatment of Alzheimer's disease

Alzheimer's disease (AD) is a degenerative disease of the nervous system. Mainly presenting with neuropsychiatric symptoms such as progressive memory impairment, cognitive dysfunction, personality changes, and language disorders [1]. Also known as senile dementia, it is the leading cause of dementia in the elderly [2]. Involved in 60-80% of all reports of dementia [3]. As the global population ages, AD prevalence and mortality rates increase. It seriously affects the quality of life of the elderly and brings a heavy economic burden and severe social problems. The tea polyphenol epigallocatechin gallate (EGCG) has preventive and therapeutic effects on Alzheimer's disease by inhibiting the amyloid formation and aggregation, antioxidant, anti-inflammatory, metal chelating, binding cholinesterase, thereby reducing the degradation of acetylcholine, and repairing mitochondrial dysfunction. This article reviews the research on the mechanism of EGCG action on Alzheimer's disease.

Targeting at cancer energy metabolism and lipid droplet formation as new treatment strategies for epigallocatechin-3-gallate (EGCG) in colorectal cancer cells

• EGCG inhibits viability of colorectal cancer (CRC) cells via AMPK activation. • EGCG inhibits fatty acid de novo synthesis in CRC cells via AMPK activation. • EGCG inhibits lipid droplet formation in CRC cells via AMPK activation. • EGCG inhibits energy metabolism (mitochondrial oxidation/glycolysis) in CRC cells. Fatty acid metabolic reprogramming is an important hallmark of cancer cells. In this study, we examined the effects of the green tea polyphenol EGCG on fatty acid and energy metabolisms in colorectal cancer (CRC) cells. EGCG significantly inhibited the viability of HCT116 and HT-29 cancer cells, accompanied by decreased lipid droplet formation and triglyceride contents. EGCG deregulated the expression of the key genes involved in fatty acid de novo synthesis, lipid uptake, lipolysis, fatty acid β oxidation, and thermogenesis at both the mRNA and protein levels. Besides, EGCG decreased the mitochondrial oxygen consumption rate (OCR), cytosolic glycolysis, and ATP production in CRC cells. Moreover, EGCG activated AMPK in CRC cells, whereas AMPK inhibitor Compound C increased the cell viability, expression of FASN, and lipid droplet formation in HCT116 cells when cotreated with EGCG. Collectively, EGCG may serve as a potent fatty acid and energy metabolism regulator to inhibit CRC.

The green tea polyphenol EGCG is differentially associated with telomeric regulation in normal human fibroblasts versus cancer cells

Introduction: Topical investigations have demonstrated that oxidative stress and inflammation play key roles in biological aging and determine incidence and course of age-related diseases. Lifestyle and environmental factors hugely impact epigenetic regulation and DNA stability with telomere attrition and epigenetic instability providing a potential record of the cumulative burden of endogenous and exogenous oxidative noxae. Certain physiologically active plant components exhibit antioxidative activities affecting epigenetic regulation of inflammation response and DNA repair.Methods: Against this background, the present study investigated green tea polyphenol epigallocatechin gallate (EGCG) in the context of telomere regulation in Caco-2 colorectal adenocarcinoma cells vs. ES-1 primary skin fibroblasts. Cell lines were treated with 20 and 200 µM EGCG for 36, 72 and 144 hours, respectively. Telomerase activity, relative telomere length as well as methylation status of hTERT and c-Myc from different culture conditions were assessed. Malondialdehyde (MDA) served as a surrogate marker of potential pro-oxidative effects of EGCG in a physiologically relevant tissue model.Results: EGCG incubation was associated with telomere shortening and decreased telomerase activity in Caco-2 cells, and relatively longer telomeres along with increased methylation of six 5'—C—phosphate—G—3' (CpG) sites in the promoter region of human Telomerase Reverse Transcriptase (hTERT) in fibroblasts. At low concentrations, EGCG significantly decreased oxidative damage to lipids in Caco-2 cells and attenuated H2O2 induced oxidation at higher concentrations.Conclusion: These results suggest differential EGCG-mediated telomeric modulation in cancer vs. primary cells and a specific antioxidant activity of EGCG against oxidative damage to lipids in abnormal cells.Keywords: Caco-2, epigallocatechin gallate, telomeres, hTERT, DNA methylation, telomerase, oxidative stress, malondialdehyde

An Unconventional Nano-Aiegen Originating from a Natural Plant Polyphenol for Multicolor Bioimaging

The unconventional aggregation-induced emission (AIE) nature of the green tea polyphenol epigallocatechin gallate (EGCG) was first discovered and investigated by observing the disappearance and reoccurrence of fluorescence (FL) when EGCG was dissolved and recrystallized in aqueous solution. The intermolecular through-space conjugation and structural rigidification induced by multiple intermolecular H-bonds play critical roles in the AIE phenomenon. This inspired the development of a multicolored, monodisperse, photostable and nontoxic nano-AIE luminogen (nano-AIEgen), which was simply prepared by polyphenol-amine-based crosslinking in aqueous solution, and has demonstrated great potential for living cell bioimaging. The strategy to develop nano-AIEgens by assembling overlooked AIE-active hydrophilic natural products (e.g., plant polyphenols, such as tannic acid (TA), which has similar AIE characteristics) rather than traditional hydrophobic AIEgens could help expand the exploration boundary of novel, large-scale, biocompatible, water-soluble, and degradable AIE materials from natural resources.

Green tea catechins showed antibacterial activity on streptococcus mutans -An in vitro study.

The main bacterial aetiological agents in caries formation are the α-haemolytic Streptococcal species Streptococcus mutans, which has been found to be the initiator of most dental caries. The leaves of Camellia sinensis known as green tea, has properties, such as antibacterial and anti-cariogenic. Epigallocatechin-3-gallate (EGCG) one of the most abundant catechins found in green tea is known to contribute to these effects. To evaluate the antibacterial effect of green tea catechins namely EGCG on S. mutans with two different methods at different concentrations. 1) To assess the antimicrobial efficacy of EGCG by disc diffusion test at concentrations of 100, 75, and 50 μg/mL. 2) To assess the antimicrobial efficacy of EGCG by Minimum inhibitory concentration (MIC) test at concentrations ranging from 0.2 to 100 μg/mL. Commercially available purest form of green tea polyphenol EGCG was used in the study. Disc diffusion test on agar medium and MIC test was used to determine the susceptibility of the S. mutans to green tea catechins EGCG. The results of the agar well diffusion method showed that the EGCG extract has shown zones of inhibition against S. mutans at concentrations of 100 μg/mL (28.67 mm), 75 μg/mL (15.33 mm), 50 μg/mL (10.33 mm) while that of MIC test of EGCG extract of concentrations ranging from 0.2 to 100 μg/mL against S. mutans shows that the mean MIC value was 1.07. Catechins in the tea are potentially anti-cariogenic agents which can reduce bacterial presence in the oral cavity and have the potential to be further used for the preparation of dentifrice and mouthwash.

Tea polyphenol EGCG inhibited colorectal-cancer-cell proliferation and migration via downregulation of STAT3.

BackgroundGreen tea is a popular beverage worldwide and epigallocatechin-3-gallate (EGCG) is the most bioactive polyphenol in green tea. Our study aims to investigate the anti-proliferation and anti-migration effects of EGCG against colorectal-cancer SW480, SW620, and LS411N cells, and elucidate the underlying mechanism.MethodsThe in vitro anti-proliferation and anti-migration effects of EGCG against colon-cancer cells were evaluated using MTT, scratch-wound-healing, and transwell-migration assays. The effects of EGCG on apoptosis were assessed by Annexin V-FITC/PI double staining and JC-1 staining. Besides, Western blotting was employed to detect the protein-expression level and elucidate the underlying pathways. Real-time qPCR and dual-luciferase reporter assay were adopted to determine the mRNA level and promoter activity.ResultsOur results demonstrated that treatment with EGCG resulted in significant inhibition of cell proliferation by the induction of apoptosis. EGCG also inhibited SW480 cell migration in a dose-dependent manner as assessed by wound-healing and transwell-migration assays. Western blot confirmed that EGCG induced apoptosis by the activation of Caspase-3 and PARP. In addition, both STAT3 and phosphorylated STAT3 (p-STAT3) were downregulated significantly by EGCG in three selected colorectal-cancer cell lines. EGCG treatment also resulted in a significant decrease in Bcl-2, MCL-1, and Vimentin, and an increase in E-cadherin. When STAT3 was inhibited, EGCG showed no obvious effect on cell proliferation and migration. Further investigation by luciferase-reporter-activity assay showed that EGCG suppressed the promoter activity of STAT3 and downregulated the transcription of STAT3.ConclusionOur study presents evidence on the anti-proliferation and anti-migration effects of EGCG against colorectal-cancer SW480, SW620, and LS411N cells by downregulating the expression of STAT3 and suggests that EGCG could be an effective and natural supplement for colon-cancer treatment.

Natural Compounds Modulate Drug Transporter Mediated Oral Cancer Treatment

Oral cancer (OC) is a serious health problem. Surgery is the best method to treat the disease but might reduce the quality of life of patients. Photodynamic therapy (PDT) may enhance quality of life but with some limitations. Therefore, the development of a new strategy to facilitate PDT effectiveness has become crucial. ATP-binding cassette G2 (ABCG2) is a membrane protein-associated drug resistance and stemness in cancers. Here, we examined whether ABCG2 plays an important role in regulating the treatment efficacy of PDT and whether ABCG2 inhibition by natural compounds can promote the effect of PDT in OC cells. Several head and neck cancer cells were utilized in this study. OECM1 and SAS cells were selected to investigate the relationship between ABCG2 expression and protoporphyrin IX (PpIX) accumulation. Western blot analysis, flow cytometry analysis, and survival probability were performed to determine PDT efficacy and cellular stemness upon treatment of different dietary compounds, including epigallocatechin gallate (EGCG) and curcumin. In this study, we found that ABCG2 expression varied in OC cells. Hypoglycemic culture for SAS cells enhanced ABCG2 expression as higher ABCG2 expression was associated with lower PpIX accumulation and cellular stemness in OC cells. In contrast, suppression of ABCG2 expression by curcumin and tea polyphenol EGCG led to greater PpIX accumulation and enhanced PDT treatment efficiency in OC cells. In conclusion, ABCG2 plays an important role in regulating the effect of PDT. Change in glucose concentration and treatment with natural compounds modulated ABCG2 expression, resulting in altered PDT efficacy for OC cells. These modulations raise a potential new treatment strategy for early-stage OCs.

Distinguishing the Effect on the Rate and Yield of Aβ42 Aggregation by Green Tea Polyphenol EGCG.

Deposition of Aβ42 aggregates in the form of amyloid plaques is a pathological hallmark of Alzheimer’s disease. A desired avenue of intervention is the inhibition of Aβ42 aggregation. Epigallocatechin gallate (EGCG), the main polyphenol in green tea, has been generally considered an inhibitor of Aβ aggregation. However, previous experiments focused on the reduction of the amount of Aβ42 aggregates, while the effect of EGCG on the rate of Aβ42 aggregation was not critically analyzed. Here we performed an experimental evaluation of Aβ42 aggregation kinetics in the absence and presence of EGCG at a wide range of concentrations. We found that EGCG reduced thioflavin T fluorescence in an EGCG concentration-dependent manner, suggesting that EGCG reduced the amount of Aβ42 fibrils. The effect of EGCG on the rate of Aβ42 aggregation appears to be bimodal. We found that higher EGCG-to-Aβ42 ratios promoted the rate of Aβ42 aggregation, while lower EGCG-to-Aβ42 ratios inhibited the aggregation rate. To confirm that the reduction of thioflavin T fluorescence is due to the lowered aggregate quantity, but not due to perturbation of thioflavin T binding to Aβ42 fibrils, we probed the effect of EGCG on Aβ42 aggregation using site-directed spin labeling. Electron paramagnetic resonance of spin-labeled Aβ42 aggregates suggests that high EGCG-to-Aβ42 ratios led to a greatly reduced amount of Aβ42 fibrils, and these aggregates adopt similar structures as the fibrils in the no-EGCG sample. Potential implications of this work in designing prevention or therapeutic strategies using EGCG are discussed.