Protective Effects Of Epigallocatechin-3-gallate Research Articles

Epigallocatechin-3-gallate confers protection against myocardial ischemia/reperfusion injury by inhibiting ferroptosis, apoptosis, and autophagy via modulation of 14–3-3η

Previous studies have demonstrated that the underlying mechanisms of myocardial ischemia/reperfusion injury (MIRI) are complex and involve multiple types of regulatory cell death, including ferroptosis, apoptosis, and autophagy. Thus, we aimed to identify the mechanisms underlying MIRI and validate the protective role of epigallocatechin-3-gallate (EGCG) and its related mechanisms in MIRI. An in vivo and in vitro models of MIRI were constructed. The results showed that pretreatment with EGCG could attenuate MIRI, as indicated by increased cell viability, reduced lactate dehydrogenase (LDH) activity and apoptosis, inhibited iron overload, abnormal lipid metabolism, preserved mitochondrial function, decreased infarct size, maintained cardiac function, decreased reactive oxygen species (ROS) level, and reduced TUNEL-positive cells. Additionally, EGCG pretreatment could attenuate ferroptosis, apoptosis, and autophagy induced by MIRI via upregulating 14–3–3η protein levels. Furthermore, the protective effects of EGCG could be abolished with pAd/14–3–3η-shRNA or Compound C11 (a 14–3–3η inhibitor) but not pAd/NC-shRNA. In conclusion, EGCG pretreatment attenuated ferroptosis, apoptosis, and autophagy by mediating 14–3–3η and protected cardiomyocytes against MIRI.

Protective effects of EGCG on acrolein-induced Caenorhabditis elegans and its mechanism of life extension.

In this study, it was found that epigallocatechin-3-gallate (EGCG) could extend the lifespan of Caenorhabditis elegans (C. elegans) induced by 100 μM acrolein (ACR) at all test concentrations (300, 400, 500, 600, and 700 μM). Notably, 500 μM EGCG exhibited the most significant mean lifespan extension, increasing it by approximately 32.5%. Furthermore, 500 μM EGCG effectively reduced elevated levels of reactive oxygen species (ROS) and lipofuscin production caused by acrolein. It also bolstered the activity of antioxidant enzymes and mitigated malondialdehyde (MDA) levels compared to the ACR-only group. These effects appeared independent of dietary restrictions. Additionally, qPCR results revealed different changes in the transcription levels of 11 genes associated with antioxidative and anti-aging functions following EGCG treatment. At the expression level, GST-4::GFP, SOD-3::GFP and HSP-16.2::GFP exhibited an initial increase with ACR treatment followed by a decrease with EGCG treatment, while the expression pattern of these three GFPs remained consistent with the enzyme activity and transcription regulation level. EGCG treatment also reduced the nuclear localization of SKN-1 and DAF-16 in the MAPK and IIS pathways that were enhanced by ACR. Moreover, the longevity-promoting effects of EGCG were diminished or absent in 13 longevity gene-deletion mutants. In conclusion, EGCG demonstrates protective effects on ACR-induced C. elegans, with the IIS and MAPK pathways playing a critical role in enhancing resilience to ACR.

Epigallocatechin-3-gallate attenuates arsenic-induced fibrogenic changes in human kidney epithelial cells through reversal of epigenetic aberrations and antioxidant activities.

Renal fibrosis is a pathogenic intermediate stage of chronic kidney disease (CKD). Nephrotoxicants including arsenic can cause kidney fibrosis through induction of oxidative stress and epigenetic aberrations. Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, is known to have antioxidant and epigenetic modulation properties. Whether EGCG, through its antioxidant and epigenetic modulating activities, can attenuate fibrogenesis is not known. Therefore, the objective of this study was to determine whether EGCG can attenuate arsenic-induced acute injury and long-term exposure associated fibrogenicity in kidney epithelial cells. To address this question, two human kidney epithelial cell lines Caki-1 and HK-2 exposed to arsenic for both acute and long-term durations were treated with EGCG. The protective effect of EGCG on arsenic-induced cytotoxicity and fibrogenicity were evaluated by measuring the cell growth, reactive oxygen species (ROS) production, genes expression, and epigenetic changes in histone marks. Results revealed that EGCG has a protective effect in arsenic-induced acute cytotoxicity in these cells. EGCG scavenges the increased levels of ROS in arsenic exposed cells. Aberrant expression of fibrogenic genes in arsenic exposed cells were restored by EGCG. Abrogation of arsenic-induced fibrogenic changes was also associated with EGCG-mediated restoration of arsenic-induced aberrant expression of epigenetic regulatory proteins and histone marks. Novel findings of this study suggest that EGCG, through its antioxidant and epigenetic modulation capacities, has protective effects against arsenic-induced cytotoxicity and fibrogenic changes in kidney epithelial cells.

Epigallocatechin-3-gallate promotes wound healing response in diabetic mice by activating keratinocytes and promoting re-epithelialization.

Type 2 diabetes (T2D) is a metabolic disorder that causes numerous complications including impaired wound healing and poses a significant challenge for the management of diabetic patients. Epigallocatechin-3-gallate (EGCG) is a natural polyphenol that exhibits anti-inflammatory and anti-oxidative benefits in skin wounds, however, the direct effect of EGCG on epidermal keratinocytes, the primary cells required for re-epithelialization in wound healing remains unknown. Our study aims to examine the underlying mechanisms of EGCG's ability to promote re-epithelialization and wound healing in T2D-induced wounds. Murine models of wound healing in T2D were established via feeding high-fat high-fructose diet (HFFD) and the creation of full-thickness wounds. Mice were administered daily with EGCG or vehicle to examine the wound healing response and underlying molecular mechanisms of EGCG's protective effects. Systemic administration of EGCG in T2D mice robustly accelerated the wound healing response following injury. EGCG induced nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and promoted cytokeratin 16 (K16) expression to activate epidermal keratinocytes and robustly promoted re-epithelialization of wounds in diabetic mice. Further, EGCG demonstrated high binding affinity with Kelch-like ECH-associated protein 1 (KEAP1), thereby inhibiting KEAP1-mediated degradation of NRF2. Our findings provide important evidence that EGCG accelerates the wound healing response in diabetic mice by activating epidermal keratinocytes, thereby promoting re-epithelialization of wounds via K16/NRF2/KEAP1 signaling axis. These mechanistic insights into the protective effects of EGCG further suggest its therapeutic potential as a promising drug for treating chronic wounds in T2D.

The protective effects of EGCG was associated with HO-1 active and microglia pyroptosis inhibition in experimental intracerebral hemorrhage

Intracerebral hemorrhage (ICH), which has high mortality and disability rate is associated with microglial pyroptosis and neuroinflammation, and the effective treatment methods are limited Epigallocatechin-3-gallate (EGCG) has been found to play a cytoprotective role by regulating the anti-inflammatory response to pyroptosis in other systemic diseases. However, the role of EGCG in microglial pyroptosis and neuroinflammation after ICH remains unclear. In this study, we investigated the effects of EGCG pretreatment on neuroinflammation-mediated neuronal pyroptosis and the underlying neuroprotective mechanisms in experimental ICH. EGCG pretreatment was found to remarkably improved neurobehavioral performance, and decreased the hematoma volume and cerebral edema in mice. We found that EGCG pretreatment attenuated the release of hemin-induced inflammatory cytokines (IL-1β, IL-18, and TNF-α). EGCG significantly upregulated the expression of heme oxygenase-1 (HO-1), and downregulated the levels of pyroptotic molecules and inflammatory cytokines including Caspase-1, GSDMD, NLRP3, mature IL-1β, and IL-18. EGCG pretreatment also decreased the number of Caspase-1-positive microglia and GSDMD along with NLRP3-positive microglia after ICH. Conversely, an HO-1-specific inhibitor (ZnPP), significantly inhibited the anti-pyroptosis and anti-neuroinflammation effects of EGCG. Therefore, EGCG pretreatment alleviated microglial pyroptosis and neuroinflammation, at least in part through the Caspase-1/GSDMD/NLRP3 pathway by upregulating HO-1 expression after ICH. In addition, EGCG pretreatment promoted the polarization of microglia from the M1 phenotype to M2 phenotype after ICH. The results suggest that EGCG is a potential agent to attenuate neuroinflammation via its anti-pyroptosis effect after ICH.

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.

Protective effects of epigallocatechin gallate in the mice induced by chronic scrotal hyperthermia

One of the most common complications of chronic scrotal hyperthermia (SHT) is a serious disorder in the male reproductive system. The most important factor in the occurrence of these disorders is oxidative stress. Currently, we investigated the effects of epigallocatechin gallate (EGCG), as a highly potent antioxidant, against cells and tissue disorders in mice affected by chronic SHT. Fifty-six male adult NMRI mice were allocated into seven equal groups. Except the non-treated (Control) group, six other groups were exposed to heat stress. Two treated groups including Preventive and Curative received oral administration of EGCG (50 mg/kg/day) starting immediately before heat exposure and fifteen consecutive days after the end of the heat exposure, respectively. For each treated group, two subgroups including positive control (Pre/Cur + PC groups) and vehicle (Pre/Cur + vehicle groups) were considered. At the end of the study, sperm characteristics, testosterone levels, stereological parameters, apoptosis, oxidant state, and molecular assessments were performed. We found that the sperm parameters, testosterone levels, the numerical density of spermatogonia, primary spermatocytes, spermatids, sertoli, leydig cells, and seminiferous tubules, biochemical factors (except MDA), and expression of c-kit gene were significantly higher in the Preventive and Curative groups, especially in Preventive ones, compared to other groups (P < 0.05). This is while expression of HSP72 and NF-κβ genes, MDA levels, as well as density of apoptotic cells considerably decreased in both EGCG-treated groups compared to other groups and it was more pronounced in Preventive ones (P < 0.05). Generally, EGCG attenuated cellular and molecular disorders induced by heat stress in the testis and it was more pronounced in Preventive status.

Epigallocatechin Gallate Attenuates Gentamicin-Induced Nephrotoxicity by Suppressing Apoptosis and Ferroptosis

Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.

Epigallocatechin-3-gallate ameliorates liver injury secondary to Pseudomonas aeruginosa pneumonia

Pseudomonas aeruginosa is a dangerous pathogen causing nosocomial pneumonia. P. aeruginosa infection-induced liver damage is another fatal threat, and antibiotic treatment is not effective in relieving P. aeruginosa virulence-triggered damage. We here evaluated the protective effect of epigallocatechin gallate (EGCG), a substance that inhibits virulence of P. aeruginosa through quorum quenching, on liver damage secondary to P. aeruginosa infection. Mice were pretreated with EGCG (20, 40, and 80 mg/kg) for 3 days, and then infected with P. aeruginosa through intratracheal instillation to model acute pneumonia. The mice were sacrificed after 24 h of infection, and samples were harvested for subsequent analysis. EGCG significantly decreased the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Histopathological changes of liver were significantly ameliorated by EGCG. It also significantly reduced oxidative stress that induced liver damage in P. aeruginosa infection, which relied not on the activation of the Nrf2-HO-1 pathway but on the upregulation of the activity of antioxidative enzymes. Then, the inflammatory response in the liver was tested. EGCG inhibited the release of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) by blocking the inflammation regulating signaling of the TLR4-myD88-NF-κB pathway. EGCG upregulated the activation of nuclear receptors to stronger the liver protective activity against P. aeruginosa infection. Conclusively, EGCG exhibited a significant hepatoprotective effective against P. aeruginosa infection.

Protective Effects of Epigallocatechin Gallate for Male Sexual Dysfunction in Streptozotocin-Induced Diabetic Rats.

Sexual dysfunction is a common problem for men with diabetes. Epigallocatechin gallate (EGCG) is known to ameliorate erectile function in aging rats. However, there has not yet been a report to evaluate its effects on diabetic male rat sexual behavior in the literature. In this study, we investigated the effects of EGCG on male sexual behavior in diabetic rats. Diabetic rats were induced by a single intraperitoneal injection of 65 mg/kg of streptozotocin. After streptozotocin injection for one week, animals were then orally treated with 40 mg/kg of EGCG or vehicle. Copulatory behavior and fasting blood glucose levels were recorded before treatment, as well as 7 and 14 days after treatment. Serum LH, testosterone, and PDE5a levels were measured by EIA assay after the last behavioral test. Data showed that diabetic rats who had diminished sexual functions demonstrated significantly increased latencies in mount, intromission, and ejaculation, as well as significant decreases in frequencies of intromission and ejaculation, compared to non-diabetic controls, indicating sexual function recovery. Lower blood glucose levels were also found in diabetic rats after EGCG treatment. Additionally, the lower LH and higher PDE5a levels in diabetic rats than controls were also noted. The findings declared that EGCG had a protective effect on male sexual behavior in diabetic rats.

Epigallocatechin-3-gallate attenuates cyclophosphamide-induced damage in mouse ovarian tissue via suppressing inflammation, apoptosis, and expression of phosphorylated Akt, FOXO3a and rpS6

This study was conducted to evaluate the protective effects of epigallocatechin-3-gallate (EGCG) against ovarian toxicity in cyclophosphamide-treated mice and to verify the possible involvement of phosphorylated Akt, FOXO3a and rpS6 in the EGCG actions. Mice received saline solution (i.p.; control) or a single dose of cyclophosphamide (200 mg/kg body weight, i.p.) or mice were pretreated with N-acetylcysteine (150 mg/kg body weight, i.p.; positive control) or with EGCG (5, 25 or 50 mg/kg body weight, i.p.) once daily for three days followed by injection with single dose of cyclophosphamide (200 mg/kg body weight, i.p.). Thereafter, the mice were euthanized, and the ovaries were harvested and destined to histological (follicular morphology and activation), immunohistochemistry (cleaved caspase-3 and TNF-α) and fluorescence (mitochondrial activity and GSH concentrations) analyses. Furthermore, we examined the participation of p-Akt, p-FOXO3a and p-rpS6 in the protective effects of EGCG in cyclophosphamide-induced ovarian damage by immunohistochemical staining. The results showed that pretreatment with N-acetylcysteine or EGCG at 25 and 50 mg/kg before cyclophosphamide administration preserved the normal follicular morphology, prevented primordial follicle loss, reduced atresia, inflammation, and mitochondrial damage, and increased GSH concentrations compared to the only cyclophosphamide treatment. Additionally, pretreatment with 25 mg/kg EGCG regulated phosphorylated Akt, FOXO3a and rpS6 after cyclophosphamide treatment. In conclusion, short-time pretreatment with 25 mg/kg EGCG can prevent follicle loss in cyclophosphamide-treated mice by reducing oxidative damage, inflammation, and apoptosis, and regulating of p-Akt, p-FOXO3a and p-rpS6.

Analysis of the role and mechanism of EGCG in septic cardiomyopathy based on network pharmacology.

BackgroundSeptic cardiomyopathy (SC) is a common complication of sepsis that leads to an increase in mortality. The pathogenesis of septic cardiomyopathy is unclear, and there is currently no effective treatment. EGCG (epigallocatechin gallate) is a polyphenol that has anti-inflammatory, antiapoptotic, and antioxidative stress effects. However, the role of EGCG in septic cardiomyopathy is unknown.MethodsNetwork pharmacology was used to predict the potential targets and molecular mechanisms of EGCG in the treatment of septic cardiomyopathy, including the construction and analysis of protein-protein interaction (PPI) network, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and molecular docking. The mouse model of septic cardiomyopathy was established after intraperitoneal injection of LPS (lipopolysaccharide). The myocardial protective effect of EGCG on septic mice is observed by cardiac ultrasound and HE staining. RT-PCR is used to verify the expression level of the EGCG target in the septic cardiomyopathy mouse model.ResultsA total of 128 anti-SC potential targets of EGCGareselected for analysis. The GO enrichment analysis and KEGG pathway analysis results indicated that the anti-SC targets of EGCG mainly participate in inflammatory and apoptosis processes. Molecular docking results suggest that EGCG has a high affinity for the crystal structure of six targets (IL-6 (interleukin-6), TNF (tumor necrosis factor), Caspase3, MAPK3 (Mitogen-activated protein kinase 3), AKT1, and VEGFA (vascular endothelial growth factor)), and the experimental verification result showed levated expression of these 6 hub targets in the LPS group, but there is an obvious decrease in expression in the LPS + EGCG group. The functional and morphological changes found by echocardiography and HE staining show that EGCG can effectively improve the cardiac function that is reduced by LPS.ConclusionOur results reveal that EGCG may be a potentially effective drug to improve septic cardiomyopathy. The potential mechanism by which EGCG improves myocardial injury in septic cardiomyopathy is through anti-inflammatory and anti-apoptotic effects. The anti-inflammatory and anti-apoptotic effects of EGCG occur not only through direct binding to six target proteins (IL-6,TNF-α, Caspase3, MAPK3, AKT1, and VEGFA) but also by reducing their expression.

Epigallocatechin gallate enhances human lens epithelial cell survival after UVB irradiation via the mitochondrial signaling pathway.

The aim of the present study was to explore the mechanism underlying the ultraviolet B (UVB) irradiation-induced apoptosis of human lens epithelial cells (HLECs), and to investigate the protective effect of epigallocatechin gallate (EGCG) against the UVB-induced apoptosis of HLECs. HLECs were exposed to different concentrations of EGCG plus UVB (30 mJ/cm2). Cell viability was determined using the MTT assay. Furthermore, mitochondrial membrane potential (Δψm) and apoptosis were assessed by flow cytometry with JC-1 and Annexin V/PI staining, respectively. Moreover, the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as the levels of GSH, hydrogen peroxide (H2O2) and hydroxyl free radicals were determined using biochemical assay techniques. Reverse transcription-quantitative PCR and western blotting were used to detect the mRNA and protein expression levels of Bcl-2, Bax, cytochrome c, caspase-9 and caspase-3, respectively. The results revealed that UVB irradiation reduced the Δψm of HLECs and induced apoptosis. Notably, EGCG significantly attenuated the generation of H2O2 and hydroxyl free radicals caused by UVB irradiation in HLECs, and significantly increased CAT, SOD and GSH-Px activities, however, the GSH levels were not significantly increased. EGCG also reduced UVB-stimulated Bax, cytochrome c, caspase-9 and caspase-3 expression, and elevated Bcl-2 expression, suggesting that EGCG may possess free radical-scavenging properties, thus increasing cell viability. In conclusion, EGCG may be able to protect against UVB-induced HLECs apoptosis through the mitochondria-mediated apoptotic signaling pathway, indicating its potential application in clinical practice.

Effect of EGCG on bronchial epithelial cell premalignant lesions induced by cigarette smoke and on its CYP1A1 expression.

Epigallocatechin-3-gallate (EGCG) has been demonstrated to exhibit anticancer effects; however, the mechanisms behind these are not yet clear. The objective of the present study was to assess the effect of EGCG on smoking-induced, precancerous, bronchial epithelial cell lesions and determine a potential protective mechanism. Human bronchial epithelial (HBE) cells were treated with cigarette smoke extract (CSE). Benzopyrene-DNA adducts were detected by immunofluorescence cytochemistry. Changes to microRNA (miRNA) expression levels were detected via microarray. The effects of EGCG on smoke-induced benzopyrene-DNA adduct formation and the subsequent change in miRNA expression were analyzed. Subsequently, the protective effect of EGCG on smoke inhalation-induced precancerous lesions was investigated. The expression levels of miRNA target genes were also analyzed. After CSE treatment, benzopyrene-DNA adducts appeared in HBE cells, along with a resultant change in miRNA expression. EGCG inhibited the effects of CSE exposure; benzopyrene-DNA adduct formation was reduced and miRNA expression changes were suppressed. In vivo, EGCG significantly reduced benzopyrene-DNA adduct formation and the subsequent development of precancerous lesions in rat lungs induced by cigarette smoke inhalation. Moreover, EGCG downregulated CYP1A1 overexpression, a target gene of multiple smoking-induced miRNAs, in rat lungs. EGCG may reduce the risk of lung cancer by downregulating the expression of the key gene CYP1A1, preventing the formation of smoking-induced benzopyrene-DNA adducts and alleviating smoking-induced bronchial epithelial dysplasia and heterogeneity.

Epigallocatechin gallate and theaflavins independently alleviate cyclophosphamide-induced ovarian damage by inhibiting the overactivation of primordial follicles and follicular atresia

BackgroundCyclophosphamide (CTX), which has been used to treat common female cancers for several years, often causes ovarian damage, early menopause and infertility. However, strategies for the effective prevention and treatment of CTX-induced ovarian damage are still lacking. Epigallocatechin gallate (EGCG) and theaflavins (TFs), key molecules derived from green tea or black tea, have been shown to exert preventive effects on many ageing-related diseases. PurposeWe aimed to explore the potential preventive and protective effects of EGCG and TFs on CTX-induced ovarian damage and compare the two compounds. Study DesignSix-week-old female mice were administered a low or high dose of EGCG or TFs. The low dose was equivalent to the average daily amount of tea consumed by a drinker. MethodsWe determined the oestrous cycle and serum hormone levels to evaluate ovarian endocrine function, and we performed mating tests for reproductivity. We also assessed the follicle count and AMH level to evaluate ovarian reserve, and we performed Masson's trichrome and Sirius red staining to evaluate ovarian fibrosis. We conducted γ-H2AX and TUNEL analyses to evaluate DNA damage, and we also measured the relevant indicators of oxidative stress and follicular activation, including NRF2, HO-1, SOD2, AKT, mTOR and RPS6. ResultsEGCG and TFs treatment independently improved the ovarian endocrine function and reproductivity of mice that were administered CTX. EGCG and TFs also increased the ovarian reserve of these animals. Furthermore, EGCG and TFs alleviated oxidation-induced damage to ovarian DNA in mice by activating the NRF2/HO-1 and SOD2 pathways and reducing the apoptosis of growing follicles. At the same time, EGCG and TFs reduced the overactivation of primordial follicles by inhibiting the AKT/mTOR/RPS6 pathway. ConclusionThe present study showed that EGCG and TFs independently improved ovarian function in mice with CTX-induced ovarian damage, thereby providing useful information for designing a potential clinical strategy that will protect against chemotherapy-induced ovarian damage.

Epigallocatechin-3-Gallate Promotes the in vitro Maturation and Embryo Development Following IVF of Porcine Oocytes.

PurposeEpigallocatechin-3-gallate (EGCG) is a major ingredient of catechin polyphenols and exerts protective effects because of its strong antioxidant properties. As far as we know, there is still a lack of systematic research on the effects of EGCG on the in vitro maturation (IVM) and in vitro fertilization (IVF) of porcine oocytes. The present study aimed to determine the effects of EGCG on the IVM and IVF of porcine oocytes.MethodsPorcine oocytes were treated with different concentrations of EGCG (5, 10 and 20 µM), and the cumulus cell expansion, oocyte maturation rate, reactive oxygen species (ROS), glutathione (GSH) and malondialdehyde (MDA) levels, total antioxidant capacity were determined. The mRNA expression levels of oxidative stress- and apoptosis-associated genes were determined by quantitative real-time PCR. The cleavage rate and blastocyst rate of oocytes after 10 μM EGCG treatment during IVM and IVF were also evaluated.ResultsEGCG at 5, 10 and 20 μM significantly promoted cumulus cell expansion, and EGCG at 10 μM increased the oocyte maturation rate. EGCG (10 μM) treatment reduced the ROS and MDA levels, while increased the antioxidant capacity and GSH concentrations in the mature oocytes. The qRT-PCR results showed that EGCG treatment up-regulated the mRNA expression of catalase, glutathione peroxidase and superoxide dismutase in the mature oocytes. In addition, EGCG treatment also decreased the mRNA expression levels of Bax and caspase-3 and increased the Bcl-2 mRNA expression level in the mature oocytes. In addition, the cleavage rate and blastocyst rate of oocytes treated with 10 μM EGCG during IVM and IVF were significantly higher than those of the control group.ConclusionOur results suggest that EGCG promotes the in vitro maturation and embryo development following IVF of porcine oocytes. The protective effects of EGCG on the oocytes may be associated with its antioxidant and anti-apoptosis properties.

Preliminary Study on Hepatoprotective Effect and Mechanism of (-)-Epigallocatechin-3-gallate against Acetaminophen-induced Liver Injury in Rats.

Antipyretic acetaminophen (APAP) is a commonly used drug that generally associates with liver injury. (-)-Epigallocatechin-3-gallate (EGCG), an active polyphenol extracted from green tea, is extensively reported to have the potential to impact a variety of human diseases. However, few studies were reported regarding the protective effect of EGCG on APAP-induced liver injury and the mechanism is still unclear. In this study, in-vitro and in-vivo experiments were carried out to verify the hepatoprotective effect of EGCG against APAP-induced liver injury and explore the potential mechanism. Results indicated that EGCG effectively relieved the liver injury caused by APAP, as well as APAP-induced mitochondrial dysfunction. The protective role of EGCG was not only attributed to its antioxidant capacity; but also might be related to the protective effect on hepatic mitochondrial impairment; based on that, EGCG could improve the membrane potential and activities of the respiratory chain complexes in liver mitochondria. Our study casts a new light on the mechanism of EGCG’s hepatoprotective effect and suggests that EGCG has considerable potential in developing tonics for relieving APAP-induced liver injury.

The Role of EGCG in Breast Cancer Prevention and Therapy.

Breast cancer is the most frequent cancer in women. Green tea has been studied for breast cancer chemopreventive and possibly chemotherapeutic effects due to its high content in polyphenolic compounds, including epigallocatechin-3-gallate (EGCG). This review is based on literature research that included papers registered on the Medline® database. The research was conducted through PubMed, applying the following query: "EGCG"AND "breast cancer". The result was a total of 88 articles in which this review stands on. In vitro, EGCG shows antioxidant or pro-oxidant properties, depending on the concentration and exposure time. EGCG blocks cell cycle progression and modulates signaling pathways that affect cell proliferation and differentiation. EGCG also induces apoptosis, negatively modulates different steps involved in metastasis, and targets angiogenesis by inhibiting VEGF transcription. In vivo investigations have shown that oral administration of EGCG results in the reduction of tumor growth and in antimetastatic and antiangiogenic effects in animal xenograft and allograft models. Much remains unknown about the molecular mechanisms involved in the protective effects of EGCG on mammary carcinogenesis. In addition, more studies in vivo are necessary to determine the potential toxicity of EGCG at higher doses and to elucidate its interactions with other drugs. A protective effect of EGCG has been shown in different experimental models and under different experimental conditions, suggesting clinical implications of EGCG for breast cancer prevention and therapy. The data presented in this review support the importance of further investigations.

Protective Effects of Epigallocatechin Gallate (EGCG) on Endometrial, Breast, and Ovarian Cancers.

Green tea and its major bioactive component, (−)-epigallocatechin gallate (EGCG), possess diverse biological properties, particularly antiproliferation, antimetastasis, and apoptosis induction. Many studies have widely investigated the anticancer and synergistic effects of EGCG due to the side effects of conventional cytotoxic agents. This review summarizes recent knowledge of underlying mechanisms of EGCG on protective roles for endometrial, breast, and ovarian cancers based on both in vitro and in vivo animal studies. EGCG has the ability to regulate many pathways, including the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), inhibition of nuclear factor-κB (NF-κB), and protection against epithelial–mesenchymal transition (EMT). EGCG has also been found to interact with DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), which affect epigenetic modifications. Finally, the action of EGCG may exert a suppressive effect on gynecological cancers and have beneficial effects on auxiliary therapies for known drugs. Thus, future clinical intervention studies with EGCG will be necessary to more and clear evidence for the benefit to these cancers.

EGCG Upregulates UCP3 Levels to Protect MIN6 Pancreatic Islet Cells from Interleukin-1β-Induced Apoptosis.

ObjectiveThe protective effects of epigallocatechin gallate (EGCG) on interleukin-1β (IL-1β)-induced apoptosis were investigated in murine MIN6 pancreatic β-cells. The role of uncoupling protein-3 (UCP3) signaling in this process was also explored.MethodsAfter treatment with IL-1β and EGCG, cells were collected and analyzed. Cell viability was measured using the CCK8 assay and the function of β-cells was evaluated by analyzing insulin secretion. Detection of mitochondrial function in cells was performed by measuring mitochondrial membrane potential, the concentration of ATP and activity of ROS. Apoptosis was analyzed by Hochest33258 staining and flow cytometry. Expression levels of UCP3 were interrogated using immunohistochemistry, RT-PCR and Western blotting.ResultsCompared with the control group, IL-1β treatment (20nM) for 24 h significantly decreased cell viability and insulin secretion, damaged mitochondrial function and increased ROS activity. Results also showed increased apoptosis and a decrease in UCP3 expression levels (p<0.01). However, treatment with low (1mM) or high (5mM) concentrations of EGCG significantly decreased IL-1β-induced apoptosis (p<0.01), restored mitochondrial function and subsequently increased UCP3 levels in IL-1β-induced β-cells (p<0.01).ConclusionThese results suggest that EGCG protects against IL-1β-induced mitochondrial injury and apoptosis in β-cells through the up-regulation of UCP3.