Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol abundant in green tea, has garnered significant attention for its diverse therapeutic applications, ranging from antioxidant and anti-inflammatory effects to potential anticancer properties. Despite its immense promise, the practical utilization of EGCG in therapeutic settings as a medication has been hampered by inherent limitations of this drug, including poor bioavailability, instability, and rapid degradation. This review comprehensively explores the current challenges associated with the application of EGCG and evaluates the potential of nanoparticle-based formulations in addressing these limitations. Nanoparticles, with their unique physicochemical properties, offer a platform for the enhanced stability, bioavailability, and targeted delivery of EGCG. Various nanoparticle strategies, including polymeric nanoparticle, micelle, lipid-based nanocarrier, metal nanoparticle, and silica nanoparticle, are currently employed to enhance EGCG stability and pharmacological activity. This review concludes that the particle sizes of most of these formulated nanocarriers fall within 300 nm and their encapsulation efficiency ranges from 51% to 97%. Notably, the pharmacological activities of EGCG-loaded nanoparticles, such as antioxidative, anti-inflammatory, anticancer, and antimicrobial effects, are significantly enhanced compared to those of free EGCG. By critically analyzing the existing literature and highlighting recent advancements, this article provides valuable insights into the promising prospects of nanoparticle-mediated EGCG formulations, paving the way for the development of more effective and clinically viable therapeutic strategies.
Animals ; Humans ; Anti-Inflammatory Agents/administration & dosage* ; Antineoplastic Agents/administration & dosage* ; Antioxidants/administration & dosage* ; Biological Availability ; Catechin/analogs & derivatives* ; Micelles ; Particle Size ; Nanoparticle Drug Delivery System/chemistry*

Catechins have been proven to exert antitumor effects in different kinds of cancers. However, the underlying mechanisms have not been completely clarified yet. This study aimed to assess the effects and mechanisms of (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) on human melanoma skin A375 cells. Results showed that EGCG and ECG inhibited the proliferation of A375 cells and ECG showed better inhibitory effect. Flow cytometry analysis had shown that EGCG and ECG induced apoptosis and led to cell cycle arrest. EGCG and ECG decreased Bcl-2 expression and upregulated Caspase-3 protein level, indicating the development of apoptosis. Furthermore, EGCG and ECG could decreased mitochondrial membrane potential of A375 cells. In addition, the expression of Beclin-1, LC3 and Sirt3 were downregulated at protein levels, which known to be associated with autophagy. After autophagy was increased by rapamycin, the apoptotic trend was not change, indicating that apoptosis and autophagy are independent. Mechanistically, EGCG and ECG treatments decreased phosphorylated-AMPK (p-AMPK) and increased the ratios of p-PI3K, p-AKT and p-mTOR in melanoma cells. Conclusively, EGCG and ECG induced apoptosis via mitochondrial signaling pathway, downregulated autophagy through modulating the AMPK/mTOR and PI3K/AKT/mTOR signaling pathway. It indicated that EGCG and ECG may be utilized in human melanoma treatment.
AMP-Activated Protein Kinases/genetics* ; Apoptosis ; Autophagy ; Catechin/analogs & derivatives* ; Electrocardiography ; Humans ; Melanoma/drug therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism*

Deep venous thrombosis (DVT) poses a major challenge to public health worldwide. Endothelial cell injury evokes inflammatory and oxidative responses that contribute to thrombus formation. Tea polyphenol (TP) in the form of epigallocatechin-3-gallate (EGCG) has anti-inflammatory and oxidative effect that may ameliorate DVT. However, the precise mechanism remains incompletely understood. The current study was designed to investigate the anti-DVT mechanism of EGCG in combination with warfarin (an oral anticoagulant). Rabbits were randomly divided into five groups. A DVT model of rats was established through ligation of the inferior vena cava (IVC) and left common iliac vein, and the animals were orally administered with EGCG, warfarin, or vehicle for seven days. In vitro studies included pretreatment of human umbilical vein endothelial cells (HUVECs) with different concentrations of EGCG for 2 h before exposure to hydrogen peroxide. Thrombus weight and length were examined. Histopathological changes were observed by hematoxylin-eosin staining. Blood samples were collected for detecting coagulation function, including thrombin and prothrombin times, activated partial thromboplastin time, and fibrinogen levels. Protein expression in thrombosed IVCs and HUVECs was evaluated by Western blot, immunohistochemical analysis, and/or immunofluorescence staining. RT-qPCR was used to determine the levels of AGTR-1 and VEGF mRNA in IVCs and HUVECs. The viability of HUVECs was examined by CCK-8 assay. Flow cytometry was performed to detect cell apoptosis and ROS generation was assessed by 2',7'-dichlorofluorescein diacetate reagent. In vitro and invivo studies showed that EGCG combined with warfarin significantly reduced thrombus weight and length, and apoptosis in HUVECs. Our findings indicated that the combination of EGCG and warfarin protects HUVECs from oxidative stress and prevents apoptosis. However, HIF-1α silencing weakened these effects, which indicated that HIF-1α may participate in DVT. Furthermore, HIF-1α silencing significantly up-regulated cell apoptosis and ROS generation, and enhanced VEGF expression and the activation of the PI3K/AKT and ERK1/2 signaling pathways. In conclusion, our results indicate that EGCG combined with warfarin modifies HIF-1α and VEGF to prevent DVT in rabbits through anti-inflammation via the PI3K/AKT and ERK1/2 signaling pathways.
Animals ; Anticoagulants/pharmacology* ; Catechin/analogs & derivatives* ; Eosine Yellowish-(YS)/pharmacology* ; Fibrinogen/pharmacology* ; Hematoxylin/pharmacology* ; Human Umbilical Vein Endothelial Cells ; Humans ; Hydrogen Peroxide/pharmacology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; MAP Kinase Signaling System ; Phosphatidylinositol 3-Kinases/metabolism* ; Polyphenols/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; RNA, Messenger ; Rabbits ; Rats ; Reactive Oxygen Species/metabolism* ; Signal Transduction ; Sincalide/pharmacology* ; Tea ; Thrombin/pharmacology* ; Vascular Endothelial Growth Factor A/metabolism* ; Venous Thrombosis/pathology* ; Warfarin/pharmacology*

OBJECTIVE: To study the effect of epigallocatechin-3-gallate (EGCG) on liver lipid metabolism in rats with intrauterine growth restriction (IUGR) and related mechanism. METHODS: A rat model of IUGR was established by food restriction during entire pregnancy, and then the rats were randomly divided into an IUGR group and an EGCG group (n=8 each). The rats in the EGCG group were fed with water containing EGCG from after weaning to 10 weeks. Eight pup rats born from the pregnant maternal rats without food restriction were used as the control group. At the age of 13 weeks, body weight was measured. Blood and liver tissue samples were collected to measure fasting total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), fasting plasma glucose (FPG), fasting insulin (FINS), and liver lipids. Homeostasis model assessment of insulin resistance (HOMA-IR) and adipose insulin resistance (adipo-IR) were calculated. Pathological sections of the liver were observed and quantitative real-time PCR was used to measure the mRNA expression of related genes in the liver. RESULTS: At the age of 13 weeks, there was no significant difference in body weight between groups (P=0.067). There were significant differences between groups in FPG, FFA, FINS, HOMA-IR, and adipo-IR (P<0.05). There were no significant differences in the serum levels of TC and TG between groups (P>0.05), while the IUGR group had significantly higher levels of TC and TG in the liver than the EGCG group (P<0.05). Oil red staining showed that the IUGR group had a significant increase in hepatic lipid accumulation, while the EGCG group had certain improvement after EGCG treatment. PCR results suggested that compared with the control group, the IUGR group had significant reductions in the mRNA expression of Ampk and Adipor1 and a significant increase in the mRNA expression of Srebf1 (P<0.05), while EGCG increased the mRNA expression of Ampk and reduced the mRNA expression of Srebf1, with no significant differences in the two indices between the EGCG and control groups (P>0.05). CONCLUSIONS Early EGCG intervention can down-regulate the de novo synthesis of fatty acids through the Ampk/Srebf1 signaling pathway and reduce hepatic lipid accumulation in IUGR rats by improving insulin resistance of hepatocytes.
Animals ; Catechin ; analogs & derivatives ; Female ; Fetal Growth Retardation ; Insulin Resistance ; Lipid Metabolism ; Lipids ; Liver ; Pregnancy ; Rats

To explore the effect of epigallocatechin gallate (EGCG) on oxidative stress and Nrf2/HO-1 pathway in neurons subjected to oxygen-glucose deprivation/reperfusion (OGD/R).
 Methods: Primary cultured cerebral cortical neurons were prepared from Sprague-Dawley rats, and the OGD/R cell model was established. After pretreatment with EGCG at different concentrations (12.5, 25.0, 50.0 or 100.0 μmol/L), the neurons were subjected to OGD/R. The cell viability, reactive oxygen species (ROS) level and malondialdehyde (MDA) content were assessed after reperfusion. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were measured. The expression of Nrf2 protein in nucleus, HO-1 mRNA and protein were detected.
 Results: OGD/R treatment reduced the cell viability, elevated ROS level and MDA content, decreased SOD and GSH-Px activities. The expression of Nrf2 protein in nucleus, HO-1 mRNA and protein were increased (P<0.01). Pretreatment with EGCG promoted the survival of neurons exposed to OGD/R, decreased ROS level and MDA content while increased SOD and GSH-Px activities. The levels of Nrf2 protein in nucleus, HO-1 mRNA and protein were upregulated (P<0.01).
 Conclusion: EGCG can reduce the oxidative stress of neurons subjected to OGD/R, which may be related to activation of Nrf2/HO-1 signal pathway and enhancement of the antioxidant ability of neurons.
Animals ; Catechin ; analogs & derivatives ; pharmacology ; Cell Survival ; drug effects ; Cells, Cultured ; Gene Expression Regulation ; drug effects ; Glucose ; Heme Oxygenase-1 ; genetics ; metabolism ; NF-E2-Related Factor 2 ; genetics ; metabolism ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Oxidative Stress ; drug effects ; Oxygen ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control

BACKGROUNDEpigallocatechin-3-gallate (EGCG) has exhibited antitumor properties in several types of cancers, including nasopharyngeal carcinoma (NPC), but the molecular mechanisms underlying this function remain incompletely understood. The aim of the present study was to characterize the global impact of EGCG on the expression of microRNAs (miRNAs) in NPC cells.

METHODSUsing microarray analysis, the alterations of miRNA expression profiles were investigated in EGCG-treated CNE2 cells. Furthermore, the target genes and signaling pathways regulated by EGCG-specific miRNAs were identified using target prediction program and gene ontology analysis.

RESULTSA total of 14 miRNAs exhibited >2-fold expression changes in a dose-dependent manner after treatment with 20 μmol/L and 40 μmol/L EGCG. Totally 43, 49, and 52 target genes from these differentially expressed miRNAs were associated with the apoptosis, cell cycle regulation, and cell proliferation, respectively. A total of 66 signaling pathways, primarily involved in cancer development and lipid and glucose metabolism, were shown to be regulated by EGCG-specific miRNAs.

CONCLUSIONEGCG induces considerable alterations of miRNA expression profiles in CNE2 cells, which provides mechanistic insights into cellular responses and antitumor activity mediated by EGCG.

Antineoplastic Agents ; pharmacology ; Carcinoma ; Catechin ; analogs & derivatives ; pharmacology ; Cell Line, Tumor ; Computational Biology ; Gene Expression ; drug effects ; genetics ; Humans ; MicroRNAs ; genetics ; metabolism ; Nasopharyngeal Neoplasms ; genetics ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; drug effects ; genetics

OBJECTIVETo investigate the effect of epigallocatechin-3-gallate (EGCG) on biomodification of demineralized dentine substrate, in its permeability, hydrophobicity, and inhibition ability to collagen enzymatic degradation.

METHODSThe dentine substrates were treated with simulated pulpal pressure created by mixtures of 0.02%, 0.1% EGCG/bovine serum albumin (BSA) in acidic environment (pH4.4) for 48 h. A fluid-transport model was used to measure the fluid permeability through demineralized dentine substrate. Positive replicas of dentine substrate were fabricated before and after being subjected to acidic environment for scanning electron microscope (SEM) examination. The blank group contained no EGCG and the positive group were treated with Gluma desensitizer. Static contact angle measurements on demineralized dentin and 0.1% EGCG primed dentin were performed by contact angle analyzer. The priming time were 60 s, 120 s, 0.5 h, 1 h. Dentine specimens bonded with Adper single bond 2 were subjected to 100 mg/L collagenase and observed under SEM. Resin-bonded specimens (with 0.02%, 0.1%, 0.5% EGCG priming, or without EGCG priming) were created for micro-tensile bond strength evaluation (MTBS). Resin-bonded specimens after thermol cycling were created for MTBS evaluation.

RESULTSThe fluid permeability in the blank control group increased ([151.3±22.3]%), the fluid permeability in 0.1% EGCG/BSA group decreased ([23.7±6.3]%). Compared to the blank control group, the contact angle of 120 s, 0.5 h, 1 h groups increased by 31.0%, 53.5%, 57.8% in deep dentin and 37.4%, 59.3%, 62.4% in shallow dentin. The SEM examination showed that 0.1% and 0.5% EGCG priming for 120 s significantly increased dentin collagen's resistance to collagenase. The immediate MTBS of 0.1% and 0.5% EGCG groups were (29.4±4.8) and (19.8± 4.9) MPa. After thermol cycling, the MTBS of 0.1% and 0.5% EGCG groups were (19.9±5.1) and (15.3± 6.3) MPa.

CONCLUSIONSUnder acidic environment (pH4.4), the 0.1% EGCG can reduce dentine permeability under acidic environment. The 0.1% EGCG can increase hydrophobicity of dentin substrate, and strengthen dentin substrate's resistance to collagenase hydrolysis, thus increased the resin-dentin bonding durability.

Acid Etching, Dental ; Catechin ; analogs & derivatives ; pharmacology ; Collagen ; chemistry ; drug effects ; Collagenases ; pharmacology ; Composite Resins ; Dental Bonding ; Dental Cements ; Dental Pulp ; Dentin ; chemistry ; drug effects ; Dentin Permeability ; drug effects ; Dentin-Bonding Agents ; Glutaral ; pharmacology ; Hydrogen-Ion Concentration ; Hydrolysis ; Methacrylates ; pharmacology ; Microscopy, Electron, Scanning ; Pressure ; Resin Cements ; Serum Albumin, Bovine ; pharmacology ; Tensile Strength ; Time Factors

To study the role and molecular mechanism of epigallocatechin gallate (EGCG) in reversing drug-resistance to 5-fluorouracil (5-FU) in gastric cancer drug-resistant cell line SGC-7901/5-FU.

METHODSDrug-resistance gastric cancer cell line (SGC-7901/5-FU) was established by high doses of repeated impact joint drug concentration increment methods. The cell viability of the parent cell line and the drug-resistance cell line were determined by standard MTT assay. Cell survival rate of drug-resistance was calculated by the formula [(Aof the treatment group / Aof the control group) × 100%]. Cell half inhibitory concentration (IC) and resistance index (RI) were calculated by the Graphpad prime 6.0 software(RI=ICvalue of drug-resistance cells / ICvalue of parent cells). The apoptosis rate of SGC-7901/5-FU cells was quantified by flow cytometry after staining with annexin-V and PI. Western blot was used to detect the protein expression of drug-resistance-related proteins (ABCG2, P-gp, MDR-1 and GST-π) and apoptosis-related proteins (PARP, Survivin, Bax and bcl-2).

RESULTSICvalue was significantly increased in drug-resistant cells compared with parental cells [(64.7±3.9) mg/L and (4.1±0.3) mg/L, respectively, t=26.46, P=0.000], and the RI was 15.6. Proliferation activity in the drug-resistant cells was higher than that in parental cells at different 5-FU concentrations (all P<0.05). In drug-resistant cells, the ICvalue of 5-FU combined with EGCG group obviously decreased compared with 5-FU group [(7.3±0.1) mg/L and (63.1±1.4) mg/L respectively, t=40.84, P=0.000], and the RI was 0.12. Proliferation activity in drug-resistant cells was significantly decreased after EGCG treatment at different 5-FU concentrations (all P<0.05). Cell apoptosis rates in control group, 5-FU group, EGCG group and 5-FU combined with EGCG group were (3.0±1.0)%, (7.0±1.3)%, (6.0±1.2)% and (18.0±1.4)%, while apoptosis rate in 5-FU combined with EGCG group was significantly higher than those of other 3 groups(F=129.5, P=0.000). Western blot revealed that after EGCG treatment, the expression levels of drug-resistance-related proteins (ABCG2, P-gp, MDR-1 and GST-π) in the drug-resistant cell line SGC-7901/5-FU decreased significantly; the expression levels of apoptosis marker protein PARP and pro-apoptotic protein Bax increased significantly; and the expression levels of anti-apoptotic protein Survivin and Bcl-2 decreased significantly (all P<0.05).

CONCLUSIONEGCG can reduce the resistance of gastric cancer resistant cell line SGC-7901/5-FU, whose role may be via the inhibition of the expression of drug-resistance-related proteins, and the elevation of the protein expression ratio of PARP/Survivin and Bax/Bcl-2.

Anticarcinogenic Agents ; pharmacology ; Apoptosis ; Apoptosis Regulatory Proteins ; Catechin ; analogs & derivatives ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Drug Resistance, Neoplasm ; Fluorouracil ; pharmacology ; Humans ; Stomach Neoplasms ; drug therapy ; pathology ; bcl-2-Associated X Protein

Inflammation plays a critical role in intestinal ischemia reperfusion injury (IRI). Epigallocatechin-3-gallate (EGCG) has been demonstrated to possess anti-inflammatory effect. This study examined the effect of EGCG on intestinal IRI and explored the possible mechanisms. Male Wistar rats were randomly divided into three groups: sham-operated group (Sham), IRI control group (IRI) and IRI-EGCG group (EGCG). Rats in IRI-EGCG group were administered dissolved EGCG in drinking water (0.4 mg/mL) for 14 days prior to IRI induction. A rat model of intestinal IRI was established by ligating the superior mesenteric artery (SMA) for 30 min, followed by reperfusion for 1 h. Intestinal histology, pro-inflammatory cytokines and mediators were examined and the effect of EGCG on PI3K/Akt signalling was assessed. EGCG significantly alleviated the pathological changes of the intestine and suppressed the IRI-induced up-regulation of TNF-α, IL-1 and IL-6 mRNA and protein expression in the serum and intestine. The mechanism might be that EGCG enhanced the activation of PI3K/Akt signalling pathway. In conclusion, the administration of EGCG can significantly mitigate the acute intestinal IRI in rats by enhancing the activation of PI3K/Akt signalling pathway to suppress inflammatory response and might be a promising alternative for the prevention or treatment of intestinal IRI in the clinical practice.
Animals ; Anti-Inflammatory Agents ; administration & dosage ; pharmacology ; Catechin ; administration & dosage ; analogs & derivatives ; pharmacology ; Disease Models, Animal ; Gene Expression Regulation ; drug effects ; Interleukin-1 ; genetics ; metabolism ; Interleukin-6 ; genetics ; metabolism ; Intestines ; drug effects ; pathology ; Male ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Wistar ; Reperfusion Injury ; genetics ; metabolism ; prevention & control ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

In the study, the inhibitory effect of epigallocatechin gallate (EGCG) on Calcium oxalate nephrolithiasis and its possible mechanism were investigated. The rat Calcium oxalate nephrolithiasis model was induced through the combined oral administration of ethylene glycol and ammonium chloride, which was intervened with EGCG. Rat blood samples were collected to detect blood creatinine (Cr), blood urea nitrogen (BUN) and blood calcium. Rat urine samples were collected to observe and compare 24-hour urine volume, oxalic acid (Ox) and calcium in urine. Renal samples were collected to prepare tissue slices and observe the pathological changes in Calcium oxalate nephrolithiasis. The expression of osteopontin (OPN) in renal tissues was evaluated by Real-time PCR and Western blot. According to the results, compared with normal rats, rats in the nephrolithiasis model showed significant increases in Cr, BUN, urine Calcium, urine Ox and renal OPN expression (P < 0.05), but obvious decrease in 24-hour urine volume (P < 0.05); Compared with rats with nephrolithiasis, those processed with EGCG revealed remarkable declines in Cr, BUN, urine Calcium and urine Ox (P < 0.05), with significant rise in 24-hour urine volume (P < 0.05) in a concentration-dependent manner. Additionally, compared with the control group, nephrolithiasis rats showed significant pathological changes in Calcium oxalate calculus. After ECCG treatment, the renal pathological changes and OPN expression attenuated significantly in a concentration-dependent manner. The results showed that EGCG inhibits the formation of calcium oxalate nephrolithiasis in rats and shows a notable protective effect on renal functions.
Animals ; Blood Urea Nitrogen ; Calcium ; blood ; Calcium Oxalate ; metabolism ; Catechin ; administration & dosage ; analogs & derivatives ; Creatinine ; blood ; Disease Models, Animal ; Humans ; Kidney ; drug effects ; metabolism ; Male ; Nephrolithiasis ; blood ; drug therapy ; genetics ; Osteopontin ; genetics ; metabolism ; Rats ; Rats, Wistar