Epigallocatechin-3-gallate Group Research Articles

Epigallocatechin Gallate Protects Diabetes Mellitus Rats Complicated with Cardiomyopathy through TGF-β1/JNK Signaling Pathway.

Epigallocatechin gallate (EGCG) is the main component of rhubarb tannin, with antioxidant, anti-angiogenic, anti-cancer and antiviral activities. Diabetes mellitus (DM) is a high blood sugar and protein metabolism disorder syndrome, which is caused by absolute or relative factors, such as deficiency of insulin and oxidative stress. Diabetes cardiomyopathy (DCM) is one of the most frequent complications of DM. This study aims to explore whether EGCG can improve diabetic complication, myocardial fibrosis, in diabetic rats with an intraperitoneal injection of streptozotocin (STZ) through the transforming growth factor β1 (TGF-β1)/C-Jun N -terminal kinase (JNK) signaling pathway. 50 male SD rats were randomly divided into five groups, including the control group, model group, and EGCG drug groups (10 mg/kg, 20 mg/kg, 40 mg/kg), with 10 rats in each group. Rats, except for the control group, were intraperitoneally injected with STZ (65 mg/kg) to induce the diabetic rats model. EGCG drug groups were given distilled water according to the dose, while the control group and model group were given the same volume of distilled water for 12 weeks. The levels of glucose (GLU), triglyceride (TG), cholesterol (CHO), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in serum were detected by ELISA of all rats. Myocardial function was observed by HE, Masson staining and Sirius red staining in DCM rats. Immunohistochemistry was used to detect the expression of Collagen I (COL-I) and Collagen III (COL-III), and detect the degree of myocardial fibrosis of DM rats. Western blot was used to detect the expression of matrix metalloproteinases (MMPs), tissue inhibitor of matrix metalloproteinase (TIMPs), TGF-β1, JNK and p-JNK in the myocardium. Compared to the model group, the levels of GLU, TG, CHO, and LDL in serum were decreased while the level of HDL in serum was increased in EGCG groups rats; cardiac index and left ventricular mass index were decreased while heart function was improved in EGCG groups rats; the expressions of the COL-I and COL-III were decreased in EGCG groups, and the high dose group was the best; the expressions of TGF-β1, JNK, p-JNK, and TIMP-1 were down-regulated, and the expression of MMP-9 was up-regulated in EGCG groups. The results demonstrated that EGCG could improve STZ-induced diabetic complication, i.e., myocardial fibrosis, in diabetic rats, and protect their heart through TGF-β1/JNK signaling pathway.

(-)-Epigallocatechin Gallate Attenuates Spinal Motoneuron Death Induced by Brachial Plexus Root Avulsion in Rats.

Recent studies have indicated that epigallocatechin gallate (EGCG) benefits a variety of neurological insults. This study was performed to investigate the neuroprotective effect of EGCG after brachial plexus root avulsion in SD rats. One hundred twenty SD rats were randomized into the following three groups: an EGCG group, an Avulsion group, and a Sham group. There were 40 rats in each group. EGCG (100 mg/kg, i.p.) or normal saline was administered to rats immediately following the injuries. The treatment was continued from day 1 to day 7, and the animals were sacrificed on days 3, 7, 14, and 28 post-surgery for the harvesting of spinal cord samples for Nissl staining, immunohistochemistry (caspase-3, p-JNK, p-c-Jun), and western blot analysis (p-JNK, JNK, p-c-Jun, c-Jun). EGCG treatment caused significant increases in the percentage of surviving motoneurons on days 14 and 28 (p<0.05) compared to the control animals. On days 3 and 7 after avulsion, the numbers of caspase-3-positive motoneurons in the EGCG-treated animals were significantly fewer than in the control animals (p<0.05). The numbers of p- JNK-positive motoneurons and the ratio of p-JNK/JNK were no significant differences between the Avulsion group and the EGCG-treated group after injury at any time point. The numbers of p-c-Jun-positive motoneurons and the ratio of p-c-Jun/c-Jun were significantly lower in the EGCG-treated group compared with the Avulsion group at 3d and 7d after injury (p<0.05). Our results indicated that motoneurons were protected by EGCG against the cell death induced by brachial plexus root avulsion, and this effect was correlated with inhibiting c-Jun phosphorylation.

Epigallocatechin-3-gallate attenuates myocardial fibrosis in diabetic rats by activating autophagy.

Epigallocatechin-3-gallate (EGCG) possesses anti-fibrotic potential in diverse tissues; however, the molecular mechanisms underlying the impacts of EGCG on diabetes-induced myocardial fibrosis remain unclear. This present study aimed to unravel the anti-fibrotic effects of EGCG on the heart in type 2 diabetic rats and investigate its molecular mechanisms. Rats were randomly assigned to the following four groups: Normal (NOR), diabetic cardiomyopathy (DCM), DCM + 40 mg/kg EGCG, and DCM + 80 mg/kg EGCG groups. After 8 weeks of EGCG treatment, fasting blood glucose, left ventricular hemodynamic indices, heart index, and myocardial injury-related parameters were measured. Hematoxylin and eosin staining and Sirius Red staining were used to evaluate myocardial pathological alterations and collagen accumulation. The contents of myocardial hydroxyproline, collagen-I, collagen-III, transforming growth factor (TGF)-β1, matrix metalloprotease (MMP)-2, and MMP-9 were measured. The gene expression levels of myocardial TGF-β1, MMP-2, and MMP-9 were detected. Autophagic regulators, including adenosine 5'-monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), and autophagic markers, including microtubule-associated protein-1 light chain 3 and Beclin1 were estimated. The results indicated that diabetes significantly decreased cardiac contractile function and aggravated myocardial hypertrophy and injury. Furthermore, diabetes repressed the activation of autophagy in myocardial tissue and promoted cardiac fibrosis. Following ingestion with different doses of EGCG, myocardial contractile dysfunction, hypertrophy and injury were ameliorated; myocardial autophagy was activated, and myocardial fibrosis was alleviated in the EGCG treatment groups. In conclusion, these findings suggested that EGCG could attenuate cardiac fibrosis in type 2 diabetic rats, and its underlying mechanisms associated with activation of autophagy via modulation of the AMPK/mTOR pathway and then repression of the TGF-β/MMPs pathway.

Green tea catechin EGCG could prevent obesity-related precocious puberty through NKB/NK3R signaling pathway

This study aimed to explore the potential regulatory pathways of (-)-epigallocatechin-3-gallate (EGCG) in preventing obesity-related precocious puberty. A retrospective analysis on the impact of EGCG on puberty onset in obese girls was conducted on plasma samples collected from a human randomized controlled trial. In the trial, participants consumed EGCG capsules for 12 weeks. In the animal experiment, rats were divided into four groups: normal diet control (NC) group, high-fat diet (HFD) group, NC+EGCG group, and HFD+EGCG group. Blood samples were collected on postnatal days 27, 33, and 36 to detect sexual development indicators. The hypothalamic expressions of kisspeptin/Kiss1R and neurokinin B (NKB)/NK3R signaling were measured by RT-qPCR and Western blot assay. The ovary NKB protein expression was assessed by immunohistochemical assays. Serum NKB level in the EGCG group was lower than the placebo group by 0.599 ng/mL [β=−0.599, 95% CI: (−1.005, −0.193)], at the end of intervention and after adjusting for confounders (clinical study). In the animal experiment, EGCG intervention could significantly delay the vaginal opening (VO) time of rats fed with HFD. On day 33, EGCG intervention could significantly reduce serum NKB, luteinizing hormone (LH) levels, ovarian NKB protein expression, and endometrial thickness of HFD-fed rats, while EGCG intervention could remarkably increase mRNA and protein expression of NKB/NK3R. EGCG could prevent obesity-related precocious puberty through NKB/NK3R signaling pathway, which may provide a novel insight into the role of EGCG in preventing precocious puberty in obese girls.

Efficacy of Epigallocatechin-3-Gallate in Preventing Dermatitis in Patients With Breast Cancer Receiving Postoperative Radiotherapy

Safe and effective prophylactic therapies for radiation-induced dermatitis (RID) remain an unmet need. To determine if epigallocatechin-3-gallate (EGCG) solution reduces the incidence of RID in patients undergoing radiotherapy after breast cancer surgery. This phase 2 double-blind, placebo-controlled randomized clinical trial enrolled 180 patients with breast cancer receiving postoperative radiotherapy at Shandong Cancer Hospital and Institute in Shandong, China, between November 2014 and June 2019. Data analysis was performed from September 2019 to January 2020. Participants were randomly assigned (2:1) to receive either EGCG solution (660 μmol/L) or placebo (0.9% NaCl saline) sprayed to the whole radiation field from day 1 of the radiation until 2 weeks after radiation completion. The primary end point was incidence of grade 2 or worse RID, defined by the Radiation Therapy Oncology Group scale. The secondary end points included RID index (RIDI), symptom index, changes in the skin temperature measured by infrared thermal images, and safety. A total of 180 eligible patients were enrolled, of whom 165 (EGCG, n = 111; placebo, n = 54) were evaluable for efficacy (median [range] age, 46 [26-67] years). The occurrence of grade 2 or worse RID was significantly lower (50.5%; 95% CI, 41.2%-59.8%) in the EGCG group than in the placebo group (72.2%; 95% CI, 60.3%-84.1%) (P = .008). The mean RIDI in the EGCG group was significantly lower than that in the placebo group. Furthermore, symptom indexes were significantly lower in patients receiving EGCG. Four patients (3.6%) had adverse events related to the EGCG treatment, including grade 1 pricking skin sensation (3 [2.7%]) and pruritus (1 [0.9%]). In this randomized clinical trial, prophylactic use of EGCG solution significantly reduced the incidence and severity of RID in patients receiving adjuvant radiotherapy for breast cancer. It has the potential to become a new choice of skin care for patients receiving radiotherapy. ClinicalTrials.gov Identifier: NCT02580279.

Epigallocatechin-3-gallate exerts cardioprotective effects related to energy metabolism in pressure overload-induced cardiac dysfunction

BackgroundTo investigate the mechanisms of potential cardioprotective effects of epigallocatechin-3-gallate (EGCG) in pressure overload-induced cardiac dysfunction. MethodsA chronic heart failure model was established using abdominal aortic constriction (AAC) surgery, rats were divided into sham, AAC, and AAC + EGCG groups. Echocardiography and tissue section staining were performed to evaluate cardiac function and pathology, respectively. Gene expression level were detected with quantitative real-time polymerase chain reactions. Label-free quantitative proteomics was used to investigate the whole proteomes of heart, and the differentially expressed proteins were analyzed using bioinformatics methods. Western blot was performed to validate the levels and the reliability of the differential proteins. ResultsCompared with the AAC group, systolic dysfunction was improved in AAC + EGCG group after EGCG treatment. EGCG inhibited myocardial fibrosis and cardiac hypertrophy after AAC, along with reducing atrial natriuretic protein, B-type natriuretic peptide, collagen types 1 and 3 alpha 1, and transforming growth factor β-1. Quantitative proteomics identified a total of 162 differentially expressed proteins, among them, 18 were closely related to cardiovascular disorders. Bioinformatics analyses showed that EGCG played a therapeutic role mainly by changing energy metabolism processes, such as oxidative phosphorylation and lipid metabolism. Furthermore, NADH: ubiquinone oxidoreductase subunit S4, an important component of the mitochondrial respiratory chain, was increased after AAC and then reversed by EGCG, which was consistent with the proteomics results. ConclusionsEGCG may correct cardiac systolic dysfunction and prevent cardiac remodeling after heart failure via enhancing the energy metabolism, which provides us with new insights into cardioprotective effects of EGCG related to the energy metabolisms in pressure overload-induced cardiac dysfunction.

The effect of Epigallocatechin-3-Gallate (EGCG) combined with low dose sorafenib in apoptosis and Platelet-Derived Growth Factor Receptor (PDGFR) expression in hepatocellular carcinoma rats

Background: Sorafenib is a targeting therapy in Hepatocellular carcinoma (HCC) that targets Vascular Endothelial Growth Factor Receptors 1 (VEGFR-1), VEGFR-2, and VEGFR-3; Platelet-Derived Growth Factor Receptors β (PDGFR-β); c-Kit proto-oncogenes; FLT-3 genes; RET proto-oncogenes; and Raf-1 genes that have the same function in suppressing tumor cell proliferation, angiogenesis, and promotes tumor cell apoptosis; but its high cost makes necessary to reduce the dosage by combining with other agents. Epigallocatechin-3-Gallate (EGCG) has great potential in cancer treatment because of its anti-angiogenesis, induced apoptosis, and low cost. This study aimed to examine the effects of combination EGCG with low dose sorafenib compared to standard dose sorafenib in apoptosis and PDGFR expression in HCC rats Methods: Twenty-five male Wistar rats were randomly assigned into 4 groups: sham, control, EGCG+low dose sorafenib, and standard-dose sorafenib. Diethylnitrosamine (DEN) injection to induce HCC was carried out to all Wistar rats except for the sham group. After HCC was developed, the EGCG+low dose sorafenib group and standard-dose sorafenib group received the administration of the drugs for two weeks. PDGFR expression and apoptotic index were assessed in the last 3 groups. Data were analyzed using SPSS version 20 for Windows. Results: There was a non-significant difference of mean PDGFR expression level between the EGCG+low dose sorafenib group and standard-dose sorafenib group (p&gt;0.05); however, there was a lower significant difference of both groups compared to the control group (p&lt;0.05). There was a non-significant difference of apoptotic index between low dose sorafenib+EGCG group and standard-dose sorafenib group (p&gt;0.05); in addition, there were a higher not significantly different of both groups compared to the control group (p&gt;0.05). Conclusion: Combining low dose sorafenib with EGCG has a comparable effect with standard-dose sorafenib in reducing PDGFR of HCC, but not for apoptosis.

Blackening and blackening control of litopenaeus vannamei during storage at low temperature

ABSTRACT Litopenaeus vannamei easily blackens during cold storage. To inhibit blackening and improve thestorage quality of prawns, in this study, konjac glucomman (KGM)-epigallocatechin gallate (EGCG) topological microgel was formed and used for storage and preservation of prawns to improve their antioxidant properties. The effect of KGM-EGCG topological microgel on inhibiting shrimp blackening was studied by measuring the sensory evaluation score, pH value, TVB-N value, K value, PPO activity, and the effect of changes in the total number of bacteria of KGM-EGCG-treated prawnsduring storage. SEM and FTIR results showed that during the KGM-EGCG binding process, thenumber of hydrogen bond connections and the intermolecular force increased. Results also showed that the KGM microgel can effectively embed EGCG and enhance its stability to achieve a better controlled release effect. Compared with the EGCG group and untreated group, KGM-EGCG microgel has better anti-PPO activity and can better maintain the organoleptic quality and inhibitbacterial growth of Litopenaeus vannamei. Therefore, the KGM-EGCG microgel could slow down the increase in pH value, the production of volatile base nitrogen, and the increase in K value, and effectively extend the shelf life of Litopenaeus vannamei from 3 d to 6 d, providing a theoreticalbasis for the research of KGM functional gel and a reference for the deep processing and valueenhancement of green tea and shrimp.

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.

Phenolic modification of myofibrillar protein enhanced by ultrasound: The structure of phenol matters

Phenolic modification of myofibrillar protein (MPN) is an essential technology in meat processing. This paper investigated the grafting reaction of three structurally relevant polyphenols (PPs), epigallocatechin-3-gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), and MPN, in a conventional alkaline reaction and ultrasound (UT)-assisted oxidation system. EC triggered the production of more hydroxyl radicals at an equal molar concentration, resulting in a noticeable improvement of the final grafting effect. Moreover, pronounced changes in pore area on the microscopic scale was observed in MPN-EGCG, which was ascribed to the unique chemical structure of EGCG. Additionally, the antioxidant activities of the UT-assisted EGCG group were 133.89% and 103.10% higher than those of the single MPN group (PP0) and pure EGCG group, respectively. These results emphasized the importance of the chemical structure of PPs in the process of different grafting reactions.

Treating obesity using the combination of metformin and epigallocatechin-3-gallate

ObjectiveThis study aimed to investigate the anti-obesity effects of the combination of metformin and epigallocatechin-3-gallate (EGCG) in a diet-induced obese (DIO) model. MethodsMale C57BL/6J mice were fed with high-fat diet (HFD, 60% fat) to establish a DIO model. The DIO mice were administered intragastrically daily with vehicle, metformin (Met, 250 mg/kg), EGCG (200 mg/kg), or mixture of Met and EGCG (Met/EGCG; 250 and 200 mg/kg) for 32 days. Body weight was measured daily at a fixed time point. An intraperitoneal glucose tolerance test was performed on day 26 after treatments. Body composition was determined by using nuclear magnetic resonance technology. Adipose tissues and major organs were collected after culling. Gene expression in brown adipose tissue (BAT) and subcutaneous white adipose tissue (scWAT) were detected by quantitative polymerase chain reaction. ResultsCompared with the vehicle group, the body weight was significantly reduced in DIO mice in the Met and Met/EGCG groups. The weight loss rate in the Met and EGCG groups were 9.1% and 1.0%, respectively. However, Met/EGCG induced a 14.0% body weight loss, suggesting that the combination of Met and EGCG has a synergistic effect on reversing the body weight in DIO mice. Met/EGCG demonstrated beneficial effects on the subcutaneous fat, BAT, and glucose homeostasis in DIO mice. Furthermore, Met/EGCG did not significantly increase the thermogenic gene expression in BAT, whereas in scWAT, Met/EGCG showed moderate effects on the expression of specific markers of browning fat or beige fat. ConclusionMetformin and EGCG have combined treatment effect on the body weight of DIO mice. Their combination might be a promising treatment approach for obesity.

Treg/Th17 Ratio Regulation May Play an Important Role in Epigallocatechin-3-Gallate-Mediated Attenuation of Increased Afterload-Induced Cardiac Hypertrophy.

:The aim of this study was to investigate whether Treg/Th17 ratio regulation plays an important role in epigallocatechin-3-gallate (EGCG) in attenuating increased afterload-induced cardiac hypertrophy. Three-month-old male C57BL/6 mice were divided into sham + vehicle, abdominal aortic constriction (AAC) + vehicle, and AAC + EGCG groups. Intraperitoneal EGCG (50 mg/kg/d) administration was conducted. Cardiac structure and function were examined by ultrasonography. Pathology was examined by hematoxylin and eosin staining, wheat germ agglutinin staining, and Masson's trichome staining. T-lymphocyte subtypes were analyzed using immunofluorescence and flow cytometry assays. Ultrasonography showed that the ventricular wall in the AAC + vehicle group was thicker than that in the sham + vehicle group (P < 0.05). Hematoxylin and eosin staining revealed cardiomyocyte hypertrophy accompanied by a small amount of inflammatory cell infiltration in the AAC + vehicle group. The results of wheat germ agglutinin staining demonstrated the presence of hypertrophic cardiomyocytes in the AAC + vehicle group (P < 0.01). Masson's trichome staining showed cardiac fibrosis in the AAC + vehicle group, and the immunofluorescence assay revealed infiltration of CD4+ cells in both AAC + vehicle and AAC + EGCG groups. Splenic flow cytometry showed a significant increase in the proportion of Treg cells in the AAC + EGCG group (P < 0.05). The proportion of Th17 cells in the AAC + vehicle group was significantly higher than that in the sham + vehicle group (P < 0.05). In conclusion, changes in the Treg/Th17 ratio are associated with the occurrence of myocardial hypertrophy caused by increased afterload. Moreover, regulation of the Treg/Th17 ratio by EGCG may play an important role in the attenuation of myocardial hypertrophy.

Antioxidation Function of EGCG by Activating Nrf2/HO-1 Pathway in Mice with Coronary Heart Disease.

Objective To explore the effect and mechanism of epigallocatechin gallate (EGCG) in mice with coronary heart disease (CHD). Methods Firstly, a CHD model of mouse was established by feeding mice high-fat diet and randomly divided into four groups, including Model group (0.5% sodium cholate) and 10 mg/kg EGCG, 20 mg/kg EGCG, and 40 mg/kg EGCG groups. After oral administration of sodium cholate or EGCG, HE staining was conducted to assess the pathological changes of mouse cardiac tissues in each group of mice, biochemical kits to measure the levels of blood lipid and oxidative stress substance activity, and western blot to detect matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGFA), as well as expression levels of protein related to Nrf2/HO-1/NQO1 pathway in cardiac tissues. Results The mice in the CHD model appeared to have myocardial pathological damage with elevated serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C). Of note, administration of EGCG significantly attenuated myocardial injuries and improved blood lipid levels in mice in a concentration-dependent manner. The advent of EGCG significantly decreased the expression of VEGFA and MMP-2 and increased the activity of superoxide dismutase (SOD), when reducing the content of reactive oxygen species (ROS) in the myocardial tissue and upregulating the expression of HO-1, NQO1, and Nrf2. Conclusion EGCG may reduce atherosclerotic plaque and alleviate pathological damage in the cardiac tissue of CHD mice as well as improve blood lipid levels with antioxidative effect. The mechanism of its effect may be related to the activation of the Nrf2/HO-1/NQO1 antioxidant pathway in vivo of the CHD mice.

Effect of EGCG on inflammatory reaction in rats suffered cerebral ischemia/reperfusion injury.

Epigallocatechin gallate (EGCG) is the main bioactive component of polyphenols in tea, which has a variety of biological effects. The neurologic injury caused by cerebral ischemia/reperfusion (I/R) is closely related to the inflammatory reaction. The pro-inflammatory factor interleukin-1β (IL-1β) and the anti-inflammatory factor interleukin-10 (IL-10) play important roles in the regulation of inflammatory reaction. This study aims to explore the effect of EGCG on water content, myeloperoxidase (MPO) activity, IL-1β and IL-10 in brain tissues of rats suffered cerebral I/R injury. Middle cerebral artery occlusion model of SD rats was established by suture embolic method. After ischemia for 1.5 h, the nylon thread was pulled out and reperfusion was performed for 24.0 h. SD rats were randomly divided into 5 groups: a sham group, an I/R group, a EGCG1 group (I/R+12.5 mg/kg EGCG), a EGCG2 (I/R+25.0 mg/kg EGCG), and a EGCG3 group (I/R+50.0 mg/kg EGCG). The sham group was the same as the I/R group except that the middle cerebral artery was not blocked. The water content in brain tissues of rats was measured by dry and wet weight method, and MPO activity was detected by colorimetry. The levels of IL-1β and IL-10 mRNA were determined by RT-PCR, and the contents of IL-1β and IL-10 were determined by ELISA. In addition, primary cultured cortical neurons of SD rats were randomly divided into 3 groups: a control group, an oxygen-glucose deprivation/reperfusion (OGD/R) group, and an OGD/R+EGCG group (OGD/R+50.0 μmol/L EGCG). The effects of EGCG on the levels of IL-1β and IL-10 protein in neurons were assessed by Western blotting. Compared with the sham group, water content, MPO activity, the contents of IL-1β and IL-10 were significantly increased (P<0.05 or P<0.01), the mRNA expression of IL-1β and IL-10 were obviously up-regulated (both P<0.01) in cerebral tissues of rats in the I/R group. Compared with the I/R group, water content and MPO activity in cerebral tissues of rats were significantly decreased (both P<0.01), the content of IL-1β (P<0.01) were significantly decreased and IL-10 (P<0.01) were significantly increased in the EGCG3 group. Compared with the I/R group, the mRNA expression of IL-1β was obviously down-regulated and the mRNA expression of IL-10 was obviously up-regulated in the EGCG2 and the EGCG3 group (P<0.05 or P<0.01). Compared with the control group, the protein levels of IL-1β and IL-10 in neurons were significantly increased in the OGD/R group (both P<0.01). Compared with the OGD/R group, the protein expression of IL-1β was obviously down-regulated and the protein expression of IL-10 was obviously up-regulated in neurons in the OGD/R+EGCG group (both P<0.01). EGCG can inhibit the inflammatory reaction induced by cerebral I/R, which may be related to down-regulating the expression of pro-inflammatory factor IL-1β and up-regulating anti-inflammatory factor IL-10.

Caffeine and EGCG Alleviate High-Trans Fatty Acid and High-Carbohydrate Diet-Induced NASH in Mice: Commonality and Specificity.

Caffeine and epigallocatechin-3-gallate (EGCG), which respectively, are the main functional extracts from coffee and green tea, and present protective effects against non-alcoholic fatty liver diseases (NAFLD). These two beverages and their functional extracts are highly recommended as potential treatments for obesity and NAFLD in clinics; however, their pharmacodynamic effects and pharmacological mechanisms in non-alcoholic steatohepatitis (NASH) remain unclear. Therefore, the aim of this study was to explore the commonality and specificity of the pharmacodynamic effects and pharmacological mechanisms of caffeine and EGCG on NASH mice, which were fed with a high-trans fatty acid/high-carbohydrate (HFHC) diet. C57BL/6J mice were fed a normal diet (control group) or an HFHC diet (HFHC group) for 24 weeks. HFHC group mice were additionally treated with caffeine (75 mg/kg) or EGCG (100 mg/kg) for 6 weeks, using obeticholic acid (OCA,10 mg/kg) as a positive control group. The pharmacological effects of the drugs, including effects on glucose and lipid metabolism and liver inflammation and fibrosis, were evaluated. Gene expression in liver tissue samples from the different groups were assessed. Both caffeine and EGCG significantly reduced the liver manifestations of NASH induced by HFHC. The pathological aspects of liver lipid deposition, inflammation, and liver fibrosis in both groups were strongly ameliorated. Of note, most indexes were strongly reversed in the caffeine group, although AST activity, fasting blood glucose, and the HOMA-IR index were improved in the ECGC group. There were 714 differentially expressed genes between the caffeine and HFHC groups and 268 differentially expressed genes between the EGCG and HFHC groups. Twenty and 17 NASH-related KEGG signaling pathways were enriched by caffeine and EGCG. This study confirmed that 75 mg/kg caffeine and 100 mg/kg EGCG could significantly improve liver lipid deposition, glucose metabolism, inflammation, and fibrosis in a mouse model of NASH induced by HFHC. The bioinformatics platform we built for caffeine and EGCG in NASH disease found that the two drugs may greatly overlap in improving the mechanism related to NASH inflammation. However, caffeine may have better potential in regulating glucose metabolism and EGCG may have better potential in regulating lipid metabolism.

Effects of Dietary Supplementation with Epigallocatechin Gallate on Meat Quality and Muscle Antioxidant Capacity of Broilers Subjected to Acute Heat Stress.

Simple SummaryBroilers are readily affected by acute heat stress (AHS), and the development of intensive and high-density management and the occurrence of high temperatures during the summer exacerbate this problem. AHS has undesirable effects on animal immunity, meat quality, antioxidant capacity, and welfare of broilers, which can be alleviated by nutrition regulation. Epigallocatechin gallate (EGCG) has been found to reduce the damage of AHS on growth performance, antioxidant capacity, and the expression of nuclear factor erythroid 2-related 2 (Nrf2) in liver and jejunum. However, there are few reports on the effect and mechanism of action of EGCG on meat quality and antioxidant function in broilers under AHS. We demonstrated that EGCG protects against AHS-impaired meat quality by improving muscle antioxidant capacity, which seems to be associated with the activation of the Nrf2 signaling pathway. Moreover, these findings suggested that EGCG could be an effective additive to improve meat quality and muscle redox balance by regulating the Nrf2 signaling pathway.This study evaluated epigallocatechin gallate’s (EGCG’s, 400 mg/kg) effect on meat quality and muscle antioxidant status of broilers under acute heat stress (AHS). A total of 144 21-day-old male Huainan partridge chickens were randomly allocated to the EGCG-free group (12 replicates) and the EGCG group (6 replicates). On day 94, the EGCG-free group was divided into the control group (CON) and the AHS group, and then AHS group and EGCG group (identified as AHS + EGCG group) were treated with AHS (33 ± 1 °C for 12 h). AHS increased (p < 0.05) L*24h, drip loss, muscle lactic acid, malondialdehyde (MDA) contents, and kelch-like ECH-associated protein 1 (Keap1) mRNA level, and decreased (p < 0.05) eviscerated percentage, pH24h, a*, muscle total superoxide dismutase (T-SOD) activity, the ratio of T-SOD/MDA and glutathione peroxidase /MDA, glycogen content, and nuclear factor erythroid 2-related 2 (Nrf2), catalase (CAT), NAD(P)H/quinone dehydrogenase 1 (NQO1) mRNA levels. The AHS + EGCG group exhibited lower (p < 0.05) L*24h, drip loss, muscle lactic acid, MDA contents and Keap1 mRNA level, and greater (p < 0.05) eviscerated percentage, pH24h, a*, muscle T-SOD activity, the ratio of T-SOD/MDA, Nrf2, and NQO1 mRNA levels compared with the AHS group. In conclusion, EGCG protects against AHS-impaired meat quality by improving muscle antioxidant capacity, which seems to be associated with the activation of the Nrf2 signaling pathway.

Evaluation of Epigallocatechin-3-Gallate as a Radioprotective Agent During Radiotherapy of Lung Cancer Patients: A 5-Year Survival Analysis of a Phase 2 Study.

BackgroundPrevious analysis of the study (NCT02577393) had demonstrated the application of epigallocatechin-3-gallate (EGCG) could be safe and effective in the prevention and treatment of acute radiation esophagitis in patients with advanced lung cancer. EGCG seemed to improve the response rate of small cell lung cancer (SCLC) to radiotherapy in a subgroup analysis. This research continued to analyze the impact of EGCG application on cancer-radiation efficacy and patient survival.MethodsAll patients with SCLC in the NCT02577393 study were included. Patients were randomized into EGCG group or conventional therapy group as protocol. The primary endpoints of the study were radiation response rate and progression-free survival (PFS). Overall survival (OS) and the efficacy of EGCG in the treatment of esophagitis were assessed as secondary endpoints.ResultsA total of 83 patients with lung cancer in the NCT02577393 study were screened, and all 38 patients with SCLC were eligible for analysis. No significant differences with regard to baseline demographic and clinical characteristics were observed between the two groups. The objective response rate (ORR) was higher than that of conventionally treated patients (84.6 vs 50%, P = 0.045), while the median PFS and OS were not significantly prolonged. At data cut-off (1 January 2021), 5-year PFS was 33% with EGCG versus 9.3% with conventional treatment, and 5-year OS was 30.3% versus 33.3%, respectively. The mean adjusted esophagitis index and pain index of patients with EGCG application were lower than conventional treatment (5.15 ± 2.75 vs 7.17 ± 1.99, P = 0.030; 8.62 ± 5.04 vs 15.42 ± 5.04, P < 0.001).ConclusionThe study indicates EGCG may alleviate some esophagitis-related indexes in SCLC patients exposed to ionizing radiation without reducing survival. However, this conclusion should be confirmed by further studies with large sample size.

EGCG decreases myocardial infarction in both I/R and MIRI rats through reducing intracellular Ca2+ and increasing TnT levels in cardiomyocytes.

Myocardial ischemia/reperfusion injury (MIRI) usually induces serious health problems. This study attempted to explore protective effects of (-)-epigallocatechin-3-gallate (EGCG) on MIRI and the associated mechanism. Ischemia/reperfusion of an isolated rat heart (I/R model) and the MIRI model were used in this study. Myocardial infarction was measured with staining with 2,3,5-triphenyltetrazolium chloride (TTC). Ca2+ and troponin T (TnT) concentrations in coronary perfusion fluid were evaluated using the chromatometry method. Ca2+ concentration in cardiomyocytes was determined with detecting Ca2+ fluorescence intensity. The ultrastructure of cardiomyocytes was observed using transmission electron microscopy (TEM). β-nicotinamide adenine dinucleotide (NAD+) of cardiomyocytes was also determined. The EGCG (I/R+EGCG) significantly reduced myocardial infarction size of isolated rat heart compared to I/R rats (p < 0.05), remarkably increased Ca2+ and decreased TnT concentrations in coronary perfusion fluid of I/R rats compared to the I/R model (p < 0.05), as well as markedly decreased intracellular Ca2+ concentration and promoted NAD+ concentration in cardiomyocytes compared to I/R rats (p < 0.05). It also obviously maintained the mitochondrial structure in cardiomyocytes of I/R rats and improved the ultrastructure of cardiomyocytes of MIRI rats. Lonidamine (LND) treatment (I/R+EGCG+LND group) significantly blocked the effects of EGCG on I/R injury compared to the I/R+EGCG group (p < 0.05). The EGCG (MIRI+EGCG) significantly decreased myocardial infarction size compared to MIRI rats (p < 0.05) and remarkably enhanced Ca2+ and reduced TnT concentrations in the pulmonary artery compared to that of MIRI rats (p < 0.05). The EGCG decreased myocardial infarction size in both I/R models and MIRI models by reducing intracellular Ca2+ concentration, increasing TnT concentration, promoting NAD+ concentration, and improving the ultrastructure of cardiomyocytes.

The Effects of Systemic Use of Epigallocatechin Gallate in Thermal Injury Progression

The burn wound progression is a complex process caused by inadequate tissue perfusion, free radical damage, and altered cytokine levels in burn patients. Epigallocatechin gallate (EGCG) has vasodilator, antioxidant, and skin protective properties. In this study, we investigated the effects of epigallocatechin gallate (EGCG) on burn wounds. Nine male Wistar albino rats were randomly assigned to the control group and received no burn insult. The other rats were exposed to thermal injury with a brass comb and randomly divided into two groups: burn with no further treatment (group 1, n:3) and burn with enteral EGCG treatment (group 2, n:3). The administration of EGCG was initiated 5 min after the burn procedure at a dose of 1 mg/kg by gastric lavage and repeated for 3 days at an infusion rate of 1 mg/kg/day. Skin sections were stained with Hematoxylin-Eosin and Masson’s trichrome for histochemistry. The primary antibodies used for immunohistochemistry included rabbit anti-4-hydroxynonenal (protein-HNE), rabbit anti-malondialdehyde (protein-MDA, mouse monoclonal anti-acrolein (protein-ACR), rabbit anti-ALDH1A1, and rabbit anti-ALDH2. Systemic administration of EGCG after burn injury significantly ameliorated the histological alterations in burn sites, especially in the zone of stasis. The expression of reactive aldehyde products (HNE, MDA, ACR) as a result of thermal injury significantly decreased in the EGCG group. EGCG reduced reactive aldehyde products independent of ALDH1 and ALDH2 pathway and improved histological alterations with cytoprotective and antioxidant effects. Early systemic use of EGCG prevents burn wound from progressing to deep structures and limits its extension to the adjacent zones.

Effects of epigallocatechin gallate (EGCG) on the biological properties of human dental pulp stem cells and inflammatory pulp tissue

ObjectiveThis study aimed to investigate the effect of epigallocatechin gallate (EGCG) on the proliferation, mineralization, inflammation and hypoxia responses of human dental pulp stem cells (hDPSCs) in vitro and its effect on inflammatory pulp tissue in rats in vivo. DesignThe optimum concentration of EGCG was selected by creating a dose response curve. Expression of odontogenic/osteogenic-related genes and inflammatory cytokines after stimulation with Lipopolysaccharide (LPS) was detected by real-time PCR. Under hypoxic conditions, cell proliferation and expression of reactive oxygen species (ROS) and superoxide dismutase (SOD) were detected.In vivo, the maxillary first molars of SD rats were pulpotomized and stimulated with 5 mg/mL LPS for 30 min. Normal saline and EGCG were used to flush the pulp chamber. After 2 months, samples were removed for micro-CT scanning and HE staining. ResultsCCK-8 assay revealed that 10 μg/mL EGCG had no significant effect on the proliferation of hDPSCs. EGCG inhibited expression of IL-1β, IL-6, and TNF-α. Furthermore, EGCG rescued cell proliferation ability, increased SOD activity and reduced ROS expression under hypoxia.In vivo, reduced inflammatory cell accumulation was observed in the coronal pulp in the EGCG group, while in the control group, diffuse inflammatory cells were observed in the radicular pulp. ConclusionEGCG had no obvious effects on calcified nodule formation but significantly inhibited the inflammatory response of hDPSCs and inhibited apoptosis of hDPSCs caused by hypoxia injury. In vivo, EGCG exerts inhibitory effects on pulp tissue inflammation.