Green Tea Epigallocatechin Gallate Research Articles

Binding of green tea epigallocatechin gallate to the arginine kinase active site from the brown recluse spider (Loxosceles laeta): A potential synergist to chemical pesticides

Loxosceles spp. spiders can cause serious public health issues. Chemical control is commonly used, leading to health and environmental problems. Identifying molecular targets and using them with natural compounds can help develop safer and eco-friendlier biopesticides. We studied the kinetics and predicted structural characteristics of arginine kinase (EC 2.7.3.3) from Loxosceles laeta (LlAK), a key enzyme in the energy metabolism of these organisms. Additionally, we explored (−)-epigallocatechin gallate (EGCG), a green tea flavonoid, as a potential lead compound for the LlAK active site through fluorescence and in silico analysis, such as molecular docking and molecular dynamics (MD) simulation and MM/PBSA analyses. The results indicate that LlAK is a highly efficient enzyme (KmArg 0.14 mM, KmATP 0.98 mM, kcat 93 s−1, kcat/KmArg 630 s−1 mM−1, kcat/KmATP 94 s−1 mM−1), which correlates with its structure similarity to others AKs (such as Litopenaeus vannamei, Polybetes pythagoricus, and Rhipicephalus sanguineus) and might be related to its important function in the spider's energetic metabolism. Furthermore, the MD and MM/PBSA analysis suggests that EGCG interacted with LlAK, specifically at ATP/ADP binding site (RMSD <1 nm) and its interaction is energetically favored for its binding stability (−40 to −15 kcal/mol). Moreover, these results are supported by fluorescence quenching analysis (Kd 58.3 μM and Ka 1.71 × 104 M-1). In this context, LlAK is a promising target for the chemical control of L. laeta, and EGCG could be used in combination with conventional pesticides to manage the population of Loxosceles species in urban areas.

Green Tea Catechins Decrease Solubility of Raloxifene In Vitro and Its Systemic Exposure in Mice.

Green tea is a widely consumed beverage. A recent clinical study reported green tea decreased systemic exposure of raloxifene and its glucuronide metabolites by 34-43%. However, the underlying mechanism(s) remains unknown. This study investigated a change in raloxifene's solubility as the responsible mechanism. The effects of green tea extract, (-)-epigallocatechin gallate (EGCG), and (-)-epigallocatechin (EGC) on raloxifene's solubility were assessed in fasted state simulated intestinal fluids (FaSSIF) and fed state simulated intestinal fluids (FeSSIF). EGCG and EGC represent green tea's main bioactive constituents, flavan-3-gallate and flavan-3-ol catechins respectively, and the tested concentrations (mM) match the µg/mg of each compound in the extract. Our mouse study (n = 5/time point) evaluated the effect of green tea extract and EGCG on the systemic exposure of raloxifene. EGCG (1mM) and EGC (1.27mM) decreased raloxifene's solubility in FaSSIF by 78% and 13%, respectively. Micelle size in FaSSIF increased with increasing EGCG concentrations (> 1000% at 1mM), whereas EGC (1.27mM) did not change micelle size. We observed 3.4-fold higher raloxifene solubility in FeSSIF compared to FaSSIF, and neither green tea extract nor EGCG significantly affected raloxifene solubility or micelle size in FeSSIF. The mice study showed that green tea extract significantly decreased raloxifene Cmax by 44%, whereas EGCG had no effect. Green tea extract and EGCG did not affect the AUC0-24h of raloxifene or the metabolite-to-parent AUC ratio. This study demonstrated flavan-3-gallate catechins may decrease solubility of poorly water-soluble drugs such as raloxifene, particularly in the fasted state.

Understanding the mechanisms of green tea EGCG against amyloid β oligomer neurotoxicity through computational studies.

Oligomeric species of amyloid β peptide (Aβ) are pivotal in Alzheimer's disease (AD) pathogenesis, making them valuable therapeutic targets. Currently, there is no cure or preventive therapy available for AD, with only a few therapeutics offering temporary alleviation of symptoms. Natural products (NPs) are now considered promising anti-amyloid agents. Green tea catechins have garnered considerable attention due to their ability to remodel the toxic amyloid β peptide oligomers (AβOs) into non-toxic assemblies. Nevertheless, the precise molecular mechanism underlying their effects on AβOs remains unclear. In this study, we employ a combination of binding site prediction, molecular docking, and dynamics simulations to gain mechanistic insights into the binding of the potent anti-amyloid epigallocatechin-3-gallate (EGCG) and the less effective catechin, epicatechin (EC), on the structure of pore-forming Aβ tetramers (PDB ID 6RHY). This recently elucidated structure represents AβO(1-42) with two faces of the hydrophobic β-sheet core and hydrophilic edges. Our simulations revealed three potential druggable binding sites within the AβO: two in hydrophilic edges and one in the β-sheet core. Although both catechins bind via hydrogen bond (H-bond) and aromatic interactions to the three potential binding sites, EGCG interacted with key residues more efficiently than EC. We propose that EGCG may remodel AβOs preventing pore formation by binding to the hydrophilic edge binding sites. Additionally, EGCG interacts with key residues in the oligomer's β-sheet core binding site, crucial for fibrillar aggregation. A better understanding of how anti-amyloid compounds remodelling AβOs could be valuable for the development of new therapeutic strategies targeting Aβ in AD. Further experimental validation using point mutations involving key residues could be useful to define whether the establishment of these interactions is crucial for the EGCG remodelling effect.

Autologous transplantation of green tea epigallocatechin-3-gallate pretreated adipose-derived stem cells increases cardiac regenerative capability through C-X-C motif chemokine receptor 4 expression in the treatment of rats with diabetic cardiomyopathy.

Cardiomyopathy is one of complications related to diabetes. Stem cell transplantation shows potential in diabetic cardiomyopathy treatment. Epigallocatechin-3-gallate (EGCG) is one of the major components found in green tea. Although stem cell transplantation and green tea EGCG supplementation show therapeutic effects on cardiomyopathy, the detailed cellular mechanisms in stem cell transplantation coupled with EGCG treatment remain unclear. This study investigates whether adipose-derived stem cells (ADSC) pretreated with EGCG show better protective effect on diabetic cardiomyopathy than ADSC without EGCG pretreatment. A cell model indicated that ADSC pretreated with EGCG increased cell functions including colony formation, migration and survival markers. All of these functions are blocked by small interfering C-X-C motif chemokine receptor 4 (siCXCR4) administration. These findings suggest that ADSC pretreatment with EGCG increases cell functions through CXCR4 expression. A diabetic animal model was designed to verify the above findings, including Sham, DM (diabetes mellitus), DM+ADSC (DM rats receiving autologous transplantation of ADSC) and DM+E-ADSC (DM rats receiving EGCG pretreated ADSC). Compared to the Sham, we found that all of pathophysiological signalings were activated in the DM group, including functional changes (decrease in ejection fraction and fractional shortening), structural changes (disarray and fibrosis) and molecular changes (increases in apoptotic, fibrotic, hypertrophic markers and decreases in survival and longevity markers). E-ADSC (DM+E-ADSC) transplantation shows significant improvement in the above pathophysiological signalings greater than ADSC (DM+ADSC). Therefore, ADSC pretreated with EGCG may contribute to clinical applications for diabetic patients with cardiomyopathy.

Analysing potent biomarkers along phytochemicals for breast cancer therapy: an in silico approach

PurposeThis research focused on the identification of herbal compounds as potential anti-cancer drugs, especially for breast cancer, that involved the recognition of Notch downstream targets NOTCH proteins (1–4) specifically expressed in breast tumours as biomarkers for prognosis, along with P53 tumour antigens, that were used as comparisons to check the sensitivity of the herbal bio-compounds.MethodsAfter investigating phytochemical candidates, we employed an approach for computer-aided drug design and analysis to find strong breast cancer inhibitors. The present study utilized in silico analyses and protein docking techniques to characterize and rank selected bio-compounds for their efficiency in oncogenic inhibition for use in precise carcinomic cell growth control.ResultsSeveral of the identified phytocompounds found in herbs followed Lipinski’s Rule of Five and could be further investigated as potential medicinal molecules. Based on the Vina score obtained after the docking process, the active compound Epigallocatechin gallate in green tea with NOTCH (1–4) and P53 proteins showed promising results for future drug repurposing. The stiffness and binding stability of green tea pharmacological complexes were further elucidated by the molecular dynamic simulations carried out for the highest scoring phytochemical ligand complex.ConclusionThe target-ligand complex of green tea active compound Epigallocatechin gallate with NOTCH (1–4) had the potential to become potent anti-breast cancer therapeutic candidates following further research involving wet-lab experiments.

Natural Rubber/Hexagonal Mesoporous Silica Nanocomposites as Efficient Adsorbents for the Selective Adsorption of (-)-Epigallocatechin Gallate and Caffeine from Green Tea.

(-)-Epigallocatechin gallate (EGCG) is a bioactive component of green tea that provides many health benefits. However, excessive intake of green tea may cause adverse effects of caffeine (CAF) since green tea (30-50 mg) has half the CAF content of coffee (80-100 mg). In this work, for enhancing the health benefits of green tea, natural rubber/hexagonal mesoporous silica (NR/HMS) nanocomposites with tunable textural properties were synthesized using different amine template sizes and applied as selective adsorbents to separate EGCG and CAF from green tea. The resulting adsorbents exhibited a wormhole-like silica framework, high specific surface area (528-578 m2 g-1), large pore volume (0.76-1.45 cm3 g-1), and hydrophobicity. The NR/HMS materials adsorbed EGCG more than CAF; the selectivity coefficient of EGCG adsorption was 3.6 times that of CAF adsorption. The EGCG adsorption capacity of the NR/HMS series was correlated with their pore size and surface hydrophobicity. Adsorption behavior was well described by a pseudo-second-order kinetic model, indicating that adsorption involved H-bonding interactions between the silanol groups of the mesoporous silica surfaces and the hydroxyl groups of EGCG and the carbonyl group of CAF. As for desorption, EGCG was more easily removed than CAF from the NR/HMS surface using an aqueous solution of ethanol. Moreover, the NR/HMS materials could be reused for EGCG adsorption at least three times. The results suggest the potential use of NR/HMS nanocomposites as selective adsorbents for the enrichment of EGCG in green tea. In addition, it could be applied as an adsorbent in the filter to reduce the CAF content in green tea by up to 81.92%.

Preparation and anticancer actions of CuET-nanoparticles dispersed by bovine serum albumin

Diethyldithiocarbamate-copper complex (CuET) shows promising anticancer effect; nonetheless, preclinical evaluations of CuET are hindered due to poor solubility. We prepared bovine serum albumin (BSA)-dispersed CuET nanoparticles (CuET-NPs) to overcome the shortcoming. Results from a cell-free redox system demonstrated that CuET-NPs reacted with glutathione, leading to form hydroxyl radical. Glutathione-mediated production of hydroxyl radicals may help explain why CuET selectively kills drug-resistant cancer cells with higher levels of glutathione. CuET-NPs dispersed by autoxidation products of green tea epigallocatechin gallate (EGCG) also reacted with glutathione; however, the autoxidation products eradicated hydroxyl radicals; consequently, such CuET-NPs exhibited largely compromised cytotoxicity, suggesting that hydroxyl radical is a crucial mediator of CuET anticancer activity. In cancer cells, BSA-dispersed CuET-NPs exhibited cytotoxic activities equivalent to CuET and induced protein poly-ubiquitination. Moreover, the reported powerful inhibition of CuET on colony formation and migration of cancer cells could be replicated by CuET-NPs. These similarities demonstrate BSA-dispersed CuET-NPs is identical to CuET. Thus, we advanced to pilot toxicological and pharmacological evaluations. CuET-NPs caused hematologic toxicities in mice and induced protein poly-ubiquitination and apoptosis of cancer cells inoculated in mice at a defined pharmacological dose. Given high interest in CuET and its poor solubility, BSA-dispersed CuET-NPs pave the way for preclinical evaluations.

Green Tea Epigallocatechin Gallate Inhibits Preadipocyte Growth via the microRNA-let-7a/HMGA2 Signaling Pathway.

This study investigates the effect of epigallocatechin gallate (EGCG) on white and beige preadipocyte growth and explores the involvement of the miR-let-7a/HMGA2 pathway. 3T3-L1 and D12 cells are treated with EGCG. The effect of EGCG on cell proliferation and viability is evaluated, as well as microRNA (miRNA)-related signaling pathways. EGCG inhibits 3T3-L1 and D12 preadipocyte growth, upregulates miR-let-7a expression, and downregulates high-mobility group AT-hook 2 (HMGA2) mRNA and protein levels in a time- and dose-dependent manner. In addition, overexpression of miR-let-7a significantly inhibits the growth of 3T3-L1 and D12 cells and decreases HMGA2 mRNA and protein levels. MiR-let-7a inhibitor antagonizes the inhibitory effects of EGCG on the number and viability of 3T3-L1 and D12 cells. Furthermore, miR-let-7a inhibitor reverses the EGCG-induced increase in miR-let-7a expression levels and decrease in HMGA2 mRNA and protein levels. HMGA2 overexpression induces an increase in cell number and viability and antagonizes EGCG-suppressed cell growth and HMGA2 expression in 3T3-L1 and D12 preadipocytes. EGCG inhibits the growth of 3T3-L1 and D12 preadipocytes by modulating the miR-let-7a and HMGA2 pathways.

Effect of epigallocatechin gallate in green tea on preventing lens opacity and αB-crystallin aggregation in rat model of diabetes.

To evaluate the effect of epigallocatechin gallate (EGCG) in preventing lens opacity and the aggregation of lens αB-crystallin in model rats of diabetes mellitus (DM). This experimental study included Wistar rats for DM as in vivo models and divided into 5 groups. The treatment groups were administered EGCG by orally for 20d and were then assessed for their degree of lens opacity with binocular microscope and lens αB-crystallin expression from Western blot analyze. Pearson correlation test and regression analysis on EGCG exposure and final random blood sugar (RBS) obtained a significance level of P<0.05. EGCG exposure can significantly lower RBS with an R 2 of 0.5634 (56.34%). The same analysis on EGCG exposure and the degree of lens opacity obtained a significance level of P<0.05 and increased exposure to EGCG can significantly lower the degree of lens opacity with an R 2 of 0.8577 (85.77%). Correlation analysis between EGCG and the expression of lens αB-crystallin can be concluded that the higher the EGCG exposure administered, the higher the native lens αB-crystallin expression and the lower the aggregate lens αB-crystallin expression. There was also significant effect in which every 1 mg/kg body weight dose of EGCG can increase the native lens αB-crystallin expression by 0.0063 and decrease the aggregate lens αB-crystallin expression by 0.0076. The administration of EGCG at a dose of 300, 600, and 1200 mg shows a significant effect on preventing lens opacity and aggregation of αB-crystallin in diabetic rat models and this research could be a biomolecular prevention of cataract.

Green tea EGCG inhibits naïve CD4+ T cell division and progression in mice: An integration of network pharmacology, molecular docking and experimental validation

Dietary green tea epigallocatechin-3-gallate (EGCG) could attenuate experimental autoimmune encephalomyelitis via the modification of the balance of CD4+ T helper (Th) cells. Moreover, EGCG administration in vitro has a direct impact on the regulatory cytokines and differentiation of CD4+ T cells. Here, we aim to determine whether EGCG directly affects the cell division and progression in naive CD4+ T cells. We first investigate the effect of EGCG on naïve CD4+ T cell division and progression in vitro. An integrated analysis of network pharmacology and molecular docking was utilized to further identify the targets of EGCG for T cell-mediated autoimmune diseases and multiple sclerosis (MS). EGCG treatment prevented naïve CD4+ T cells from progressing through the cell cycle when stimulated with anti-CD3/CD28 antibodies. This was achieved by increasing the proportion of cells arrested in the G0/G1 phase by 8.6% and reducing DNA synthesis activity by 51% in the S phase. Furthermore, EGCG treatment inhibited the expression of cyclins (cyclin D1, cyclin D3, cyclin A, and cyclin B1) and CDKs (CDK2 and CDK6) during naïve CD4+ T cell activation in response to anti-CD3/CD28 stimulation. However, EGCG inhibited the decrease of P27Kip1 (CDKN1B) during naïve CD4+ T cell activation, whereas it inhibited the increase of P21Cip1 (CDKN1A) expression 48 h after mitogenic stimulation. The molecular docking analysis confirmed that these proteins (CD4, CCND1, and CDKN1A) are the primary targets for EGCG, T cell-mediated autoimmune diseases, and MS. Finally, target enrichment analysis indicated that EGCG may affect the cell cycle, T cell receptor signaling pathway, Th cell differentiation, and NF-κB signaling pathway. These findings reveal a crucial role of EGCG in the division and progression of CD4+ T cells, and underscore other potential targets of EGCG in T cell-mediated autoimmune diseases such as MS.

Multi-Metabolomics Coupled with Quantitative Descriptive Analysis Revealed Key Alterations in Phytochemical Composition and Sensory Qualities of Decaffeinated Green and Black Tea from the Same Fresh Leaves

The supercritical CO2-based decaffeination (SCD) method can be used to prepare decaffeinated tea, but its overall effect on the phytochemicals, volatiles, and sensory qualities of green and black teas is still unclear, and its suitability to prepare decaffeinated green and black teas still needs to be compared. This study revealed the effect of SCD on phytochemicals, volatiles, and sensory qualities in black and green tea prepared from the same tea leaves, and compared the suitability of preparing decaffeinated green and black teas using SCD. The results showed that the SCD could remove 98.2 and 97.1% of the caffeine in green and black tea, respectively. However, it can cause further losses of phytochemicals in green and black teas, specifically the loss of epigallocatechin gallate, epigallocatechin, epicatechin gallate, and gallocatechin gallate in green tea and the loss of theanine and arginine in green and black teas. After the decaffeination, both green and black teas lost some volatiles but also generated new volatiles. Especially, the fruit/flower-like aroma, ocimene, linalyl acetate, geranyl acetate, and D-limonene, were generated in the decaffeinated black tea, while herbal/green-like aroma, β-cyclocitral, 2-ethylhexanol, and safranal, were generated in the decaffeinated green tea. The overall acceptance of decaffeinated green tea decreased due to the substantial reduction in bitterness and astringency, while the overall acceptance of decaffeinated black tea significantly increased. Therefore, SCD is more suitable for the preparation of decaffeinated black tea.

Effects of Green Tea (-)-Epigallocatechin-3-Gallate (EGCG) on Cardiac Function - A Review of the Therapeutic Mechanism and Potentials.

Heart disease, the leading cause of death worldwide, refers to various illnesses that affect heart structure and function. Specific abnormalities affecting cardiac muscle contractility and remodeling and common factors including oxidative stress, inflammation, and apoptosis underlie the pathogenesis of heart diseases. Epidemiology studies have associated green tea consumption with lower morbidity and mortality from cardiovascular diseases, including heart and blood vessel dysfunction. Among the various compounds found in green tea, catechins are believed to play a significant role in producing benefits to cardiovascular health. Comprehensive literature reviews have been published to summarize the tea catechins' antioxidative, anti-inflammatory, and anti-apoptosis effects in various diseases, such as cardiovascular diseases, cancers, and metabolic diseases. However, recent studies on tea catechins, especially the most abundant (-)-Epigallocatechin-3-Gallate (EGCG), revealed their capabilities in regulating cardiac muscle contraction by directly altering myofilament Ca2+ sensitivity on force development and Ca2+ ion handling in cardiomyocytes under both physiological and pathological conditions. In vitro and in vivo data also demonstrated that green tea extract or EGCG protected or rescued cardiac function, independent of their well-known effects against oxidative stress and inflammation. This mini-review will focus on the specific effects of tea catechins on heart muscle contractility at the molecular and cellular level, revisit their effects on oxidative stress and inflammation in various heart diseases, and discuss EGCG's potential as one of the lead compounds for new drug discovery for heart diseases.

Assessment of Proximate Composition and Antioxidant Potential of Different Commercially Packaged Tea Samples in West Bengal

Background: Worldwide tea consumption as beverage ranks next to water. The high consumption of tea is attributed to richness in flavor, aroma, antioxidant properties and health benefits. Tea has complex chemical composition having catechins, flavonoids, alkaloids, carotenoids, chlorophyll, amino acids, polysaccharides, lipids, vitamins, minerals and more than 600 different volatile compounds. Methods: The present study focuses on determining the physicochemical parameters, phyto-chemical assay and microbiological qualities of commercially packaged green and black tea samples within West Bengal following standard methods. Result: The values of proximate parameters like moisture, ash, acid insoluble ash and water extractive have complied with standard specifications. High pressure liquid chromatography (HPLC) analysis quantified significantly higher polyphenol content of green tea in compare to black tea samples respectively with 65.12 ppm and 18.58 ppm with gallic acid equivalence and green tea epigallocatechin gallate (EGCG) content was found 449.28 ppm with respect to pure EGCG standard. In vitro antioxidant activity of green tea and black tea extracts as reported by IC50 value were found to be 192.97-301.08 μg/ ml and 342.54-481.91μg/ ml respectively.

Green tea epigallocatechin gallate suppresses 3T3-L1 cell growth via microRNA-143/MAPK7 pathways.

Green tea epigallocatechin gallate (EGCG) and microRNA (miRNA) molecules modulate obesity. Nevertheless, it is still unknown whether EGCG modulates fat cell growth via miRNA-related signaling. In this study, white preadipocytes were used to examine whether the antimitogenic effect of EGCG on fat cells is regulated by the miR-143/MAPK7 pathway. We showed that EGCG upregulated the levels of miR-143, but not miR-155, in 3T3-L1 preadipocytes. Moreover, EGCG downregulated MAPK7 mRNA and protein levels time- and dose-dependently. MAPK7 expression increased during 3T3-L1 cell proliferation. miR-143 overexpression in the absence of EGCG mimicked the effects of EGCG to suppress preadipocyte growth and MAPK7 expression, whereas knockdown of miR-143 antagonized the EGCG-altered levels of miR-143, MAPK7, and pERK1/2 and reversed the EGCG-inhibited cell growth. These findings suggest that EGCG inhibits 3T3-L1 cell growth via miR-143/MAPK7 pathway.

Green tea EGCG effectively alleviates experimental colitis in middle-aged male mice by attenuating multiple aspects of oxi-inflammatory stress and cell cycle deregulation.

Age-dependent increased risk of inflammatory bowel diseases such as ulcerative colitis is being increasingly realized, and yet therapies targeting this disorder within the purview of aging are limited. The present study attempted to assess the efficacy of green tea epigallocatechin gallate (EGCG) consumption in preventing the severity and progression of dextran sulphate sodium (DSS)-induced ulcerative colitis in 18months old middle-aged male mice. Acute colitis was induced in animals using DSS and protective effects of EGCG consumption were examined. Different parameters related to disease progression and molecular markers related to oxi-inflammatory stress, localized and systemic cytokine response, epithelial barrier integrity, and cell cycle progression profile were evaluated. DSS treatment induced rapid and severe symptoms of colitis such as consistently increased DAI score, shortened and inflamed colon accompanied by increased levels of inflammatory proteins (TNFα/IL-6/IL-1β) in both the colon tissue and cultured splenocytes indicating exaggerated Th1 immune response. Markers of oxidative stress increased while antioxidant defences and the expression of tight junction genes in the colonic cells were attenuated. Dysregulation in the expression of cell cycle inhibitory genes (p53/p21WAF1/p16Ink4a) indicated possible induction of colitis-induced dysplasia. On the other hand, EGCG consumption strongly attenuated all the measured ostensible as well as molecular markers of the disease progression as evidenced by improved DAI score, cellular antioxidant capacity, attenuated Th1 cytokine response both in the colon and cultured splenocytes, enhanced expression of tight junction genes, and cell cycle inhibitors thereby suggesting systemic effects of EGCG. Together, these observations suggest that drinking EGCG-rich green tea can be a significant way of managing the severity of colitis during aging.

P-306 How ProEGCG achieves superior anti-angiogenic efficacy to prevent and treat endometriosis?

Abstract Study question What are the therapeutic targets and molecular mechanisms that bring superior pharmacological effects of ProEGCG against angiogenesis in endometriosis? Summary answer ProEGCG binds to PXK and downregulates PXK-mediated EGF expression in inhibiting angiogenesis via HIF-1α pathway during the growth and development of endometriosis. What is known already Current endometriosis treatment shows great effects in managing the symptoms, but associated with significant recurrence risk and hormonal side effects. Previously, we demonstrated the greater efficacies and potency of prodrug of green tea epigallocatechin gallate (ProEGCG) over EGCG to inhibit angiogenesis and oxidative stress in experimental endometriosis mouse models ( Xu, et al., 2011; Wang, et. al., 2013; Hung, et. al. 2021). However, the therapeutic targets and molecular mechanism to bring the superior anti-angiogenic effects of ProEGCG are still not known. Study design, size, duration Efficiency of ProEGCG as preventive or therapeutic medication were compared with that of EGCG in endometriosis mice model Therapeutic targets were studied by Proteome Integral Stability Alteration and proteomic analysis (Gaetani et al.,2019) using endometriotic cells, and further validated by computational simulation, target kinetic analysis and immunostaining. Anti-angiogenic mechanism were confirmed in endometriotic cell lines and mouse models. Participants/materials, setting, methods Endometriotic (Hs832(C)T) cell line was treated with EGCG or ProEGCG to identify the binding target with chemical proteomics analysis. The stability of ProEGCG-protein complexes was assessed by molecular docking analysis and bio-layer interferometry. Gene and protein expressions of the binding targets and downstream angiogenesis pathway were assessed by qRT-PCR, ELISA and immunostaining to characterise the molecular pathways in vitro and in vivo. Main results and the role of chance ProEGCG significantly reduced the endometriotic lesions in both preventive and treatment regimens with no recurrence risk after discontinuation in mice. MTDH and PXK were identified as differential protein targets of EGCG and ProEGCG respectively in Hs832(C)T cells via proteomics analysis. Molecular docking and kinetic studies validated stabilities of the drug-target complexes. Protein expressions of MTDH and PXK were significantly higher in various kinds of human endometriotic tissues compared with normal endometrium, which were found significantly downregulated in mouse endometriotic tissues after treatment of EGCG and ProEGCG, respectively. Angiogenesis was significantly inhibited by ProEGCG and EGCG in endometriosis in mice and downstream angiogenic factors HIF-1α and VEGF were downregulated in both mRNA and protein levels. However EGCG bound to MTDH and inhibited AKT-mediated angiogenesis via AKT/PI3K signalling pathway, while ProEGCG bound to PXK and inhibited EGF-mediated angiogenesis via more profound EGF/AKT1/HIF-1α/VEGF signalling pathways. It indicated distinct and specific potency of ProEGCG as an anti-proliferation and anti-angiogenesis agent in inhibiting the endometriosis progression. Limitations, reasons for caution The crosstalk of binding targets-induced therapeutic effects in endometriosis and their corresponding effects on angiogenesis are still unclear. Clinical studies are also needed to confirm the efficacy and mechanisms in humans. Wider implications of the findings Novel drug discovery identifies an ideal pharmaceutical for clinical use in endometriosis, which alleviates the symptoms, cures the disease and prevents the recurrence. Molecular targets and mechanisms as preclinical research priorities will optimize pharmacological and physiochemical properties of new drugs, as well as maximize specificity and efficacy for endometriosis treatment. Trial registration number NA

Long-term consumption of green tea EGCG enhances murine health span by mitigating multiple aspects of cellular senescence in mitotic and post-mitotic tissues, gut dysbiosis, and immunosenescence

Cellular senescence is emerging as a major hallmark of aging, and its modulation presents an effective anti-aging strategy. This study attempted to understand the progression of cellular senescence in vivo, and whether it can be mitigated by chronic consumption of green tea catechin epigallocatechin gallate (EGCG). We profiled cellular senescence in various organs of mice at four different time-points of lifespan, and then explored the influence of EGCG consumption in impacting markers of cellular senescence, inflamm-aging, immunosenescence, and gut dysbiosis. We report that visceral adipose and intestinal tissues are highly vulnerable to cellular senescence due to an increase in DNA damage response, activation of cell cycle inhibitors, and senescence-associated secretory phenotype regulators. With advancing age, dysregulation in nutrient signaling mediators (AMPK/AKT/SIRT3/5), and a decrease in autophagy was also observed. Inflamm-aging markers (TNF-α/IL-1β) and splenic CD4/CD8 T cell ratio increased with age, while NK cell population decreased. Metagenomic analyses revealed an age-related decrease in the diversity of microbial species and an increase in the abundance of various pathogenic bacterial species. On the other hand, long-term EGCG consumption significantly attenuated markers of DNA damage, cell cycle inhibitors, senescence-associated secretory phenotype regulators, AMPK/AKT signaling, and enhanced SIRT3/5 expression and autophagy. Systemic inflamm-aging indicators decreased, while early T cell activation increased in EGCG fed animals. EGCG also suppressed the abundance of pathogenic bacteria and preserved microbial diversity. Our results suggest that adipose and intestine tissues are prone to cellular senescence and that chronic consumption of EGCG can attenuate several deleterious aspects of aging which could be implicated in developing anti-aging strategies.

Adipose-Derived Stem Cells Preincubated with Green Tea EGCG Enhance Pancreatic Tissue Regeneration in Rats with Type 1 Diabetes through ROS/Sirt1 Signaling Regulation.

Type 1 diabetes stem-cell-based therapy is one of the best therapeutic approaches for pancreatic damage treatment due to stem cell tissue regeneration. Epigallocatechin gallate (EGCG) is one of the active components found in green tea. Experimental results suggest that EGCG shows beneficial effects on cell protection. This study explores whether a better pancreatic regeneration therapeutic effect could be found in mesenchymal stem cells pretreated with EGCG compared to stem cells without EGCG pretreatment. A cell model confirmed that adipose-derived stem cells (ADSC) incubated with EGCG increase cell viability under high-glucose (HG) stress. This is due to survival marker p-Akt expression. In an animal model, type 1 diabetes induced the activation of several pathological signals, including islet size reduction, extracellular fibrotic collagen deposition, oxidative stress elevation, survival pathway suppression, apoptosis signaling induction, and Sirt1 antioxidant pathway downregulation. Ordinary ADSC transplantation slightly improved the above pathological signals. Further, EGCG-pretreated ADSC transplantation significantly improved the above pathological conditions. Taken together, EGCG-pretreated ADSCs show clinical potential in the treatment of patients with type 1 diabetes through the regeneration of damaged pancreatic tissues.

Simple Approach to Enhance Green Tea Epigallocatechin Gallate Stability in Aqueous Solutions and Bioavailability: Experimental and Theoretical Characterizations

Because of its antioxidant, antimutagenic, and anti-infectious properties, epigallocatechin gallate (EGCG) is the most interesting compound among the green tea catechins polyphenols. However, its health effects are inconclusive due to its very low bioavailability, largely due to a particular instability that does not allow EGCG to reach the potency required for clinical developments. Over the last decade, many efforts have been made to improve the stability and bioavailability of EGCG using complex delivery systems such as nanotechnology, but these efforts have not been successful and easy to translate to industrial use. To meet the needs of a large-scale clinical trial requiring EGCG in a concentrated solution to anticipate swallowing impairments, we developed an EGCG-based aqueous solution in the simplest way while trying to circumvent EGCG instability. The solution was thoroughly characterized to sort out the unexpected stability outcome by combining experimental (HPLC-UV-mass spectrometry and infrared spectroscopy) and computational (density functional theory) studies. Against all odds, the EGCG–sucrose complex under certain conditions may have prevented EGCG from degradation in aqueous media. Indeed, in agreement with the ICH guidelines, the formulated solution was shown to be stable up to at least 24 months under 2–8 °C and at ambient temperature. Furthermore, considerable improvement in bioavailability in rats, against EGCG powder formulated in hard-gel capsules, was shown after gavage. Thus, the proposed formulation may provide an easily implementable platform to administer EGCG in the context of clinical development.

Beneficial Effects of Green Tea EGCG on Skin Wound Healing: A Comprehensive Review.

Epigallocatechin gallate (EGCG) is associated with various health benefits. In this review, we searched current work about the effects of EGCG and its wound dressings on skin for wound healing. Hydrogels, nanoparticles, micro/nanofiber networks and microneedles are the major types of EGCG-containing wound dressings. The beneficial effects of EGCG and its wound dressings at different stages of skin wound healing (hemostasis, inflammation, proliferation and tissue remodeling) were summarized based on the underlying mechanisms of antioxidant, anti-inflammatory, antimicrobial, angiogenesis and antifibrotic properties. This review expatiates on the rationale of using EGCG to promote skin wound healing and prevent scar formation, which provides a future clinical application direction of EGCG.