Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control...Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control,SHR control and SHR treated with EGCG(50 mg/kg/day)or losartan(10 mg/kg/day).The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 days.Acetylcholineinduced endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of treatment.The vascular levels of reactive oxygen species,nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate were also measured.Moreover,the expression of angiotensinⅡtype 1(AT_(1))receptor protein was determined.Results:The systolic blood pressure was significantly decreased in SHR treated with EGCG.The impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR group.EGCG also significantly increased the levels of nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate,while decreasing the level of reactive oxygen species and the protein expression of AT_(1)receptor in SHR.Conclusions:EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability,which may be modulated partly by inhibition of vascular AT_(1)receptors.An increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.展开更多
Alzheimer's disease(AD)shows cognitive impairments in clinic,which is multifactorial with different etiopathogenic mechanisms such as A|3 deposition,neuroinflammation and neuronal dystrophy involved.Therefore,mult...Alzheimer's disease(AD)shows cognitive impairments in clinic,which is multifactorial with different etiopathogenic mechanisms such as A|3 deposition,neuroinflammation and neuronal dystrophy involved.Therefore,multi-targets drugs with neuroprotective,anti-amyloidogenic and anti-inflammatory properties will be effective in AD treatment.Epigallocatechin-3-gallate(EGCG)possesses a broad spectrum of pharmacological activities in the prevention and treatment of multiple neurodegenerative diseases.In the present study,we showed that oral administration of EGCG(50 mg/kg)for 4 months significantly attenuated the cognitive deficits in APP/PS1 transgenic mice,which served as AD model.Moreover,EGCG induced an improvement in dendritic integrity and expression levels of synaptic proteins in the brain of APP/PS 1 mice.And EGCG exerted obvious anti-inflammatory effects,which was manifested by alleviating microglia activation,decreasing pro-inflammatory cytokine(IL-β)and increasing anti-inflammatory cytokines(IL-10,IL-β).Furthermore,p-amyloid(AP)plaques were markedly reduced in the hippocampus of 6-month old APP/PS 1 mice after EGCG treatment.In conclusion,these findings indicate that EGCG improves AD-like cognitive impairments through neuroprotective,anti-amyloidogenic and anti-inflammatory effects,thus is a promising therapeutic can didate for AD.展开更多
AIM:To investigate the mechanism underlying the anti-inflammatory effects of epigallocatechin-3-gallate(EGCG)in lipopolysaccharide(LPS)-stimulated human retinal endothelial cells(HRECs).METHODS:HRECspre-treatedwithEGC...AIM:To investigate the mechanism underlying the anti-inflammatory effects of epigallocatechin-3-gallate(EGCG)in lipopolysaccharide(LPS)-stimulated human retinal endothelial cells(HRECs).METHODS:HRECspre-treatedwithEGCG(0-100μmol/L)were stimulated with LPS(250 ng/mL).Levels of tumor necrosis factor alpha(TNF-α),vascular endothelial growth factor(VEGF),monocyte chemotactic protein-1(MCP-1)and nitric oxide(NO)in the supernatants were determined by enzyme-linked immunosorbent assay(ELISA)and Griess assay.The protein expression of phosphorylated extracellular signal-regulated kinase(ERK)1/2 and p38 mitogen-activated protein kinases(p38)were determined by Western blot analysis.RESULTS:EGCG pre-treatment significantly inhibited the secretion of TNF-α,VEGF,MCP-1 and NO in LPSstimulated HRECs.Moreover,EGCG effectively attenuated LPS-induced activation and phosphorylation of ERK1/2 and p38 in HRECs in a dose-dependent manner.CONCLUSION:EGCG exhibited inhibitory effects on LPS-induced pro-inflammatory cytokines production by modulating ERK1/2 and p38 pathways in HRECs,suggesting EGCG as a potential candidate for antiinflammatory intervention.展开更多
AIM: To investigate the(-)-epigallocatechin-3-gallate(EGCG) binding to transforming growth factor-β(TGF-β) type Ⅱ receptor(TGFRⅡ).METHODS: The expression of α-smooth muscle actin(α-SMA) was used as a marker for ...AIM: To investigate the(-)-epigallocatechin-3-gallate(EGCG) binding to transforming growth factor-β(TGF-β) type Ⅱ receptor(TGFRⅡ).METHODS: The expression of α-smooth muscle actin(α-SMA) was used as a marker for fibrotic change inhuman lung fibroblast MRC-5 cells. The α-SMA expression level was determined by western blotting and immunohistological analysis. We examined whether the anti-fibrotic effects of EGCG on MRC-5 cells was dependent on antioxidant mechanism by using edaravone and N-acetylcysteine(NAC). The suppression effects of EGCG on Smad2/3 activation were studied by confocal fluorescence microscopy. The binding of EGCG to recombinant TGFRⅡ protein was analyzed by immunoprecipitation and affinity chromatography.RESULTS: When MRC-5 cells were treated with TGF-β, EGCG decreased the expression of α-SMA in a dose dependent manner, whereas catechin did not influence the α-SMA expression in the cells. Except for EGCG, antioxidant compounds(e.g., edaravone and NAC) had no effects on the TGF-β-induced α-SMA expression. Nuclear localization of phosphorylated Smad2/3 was observed after TGF-β treatment; however, EGCG treatment attenuated the nuclear transportation of Smad2/3 in the presence or absence of TGF-β. After a TGFRⅡ expression vector was introduced into COS-7 cells, cell lysates were untreated or treated with EGCG or catechin. The immunoprecipitation experiments using the lysates showed that EGCG dose-dependently bound to TGFRⅡ and that catechin did not at all. Affinity chromatography study indicated that EGCG would bind to TGFRⅡ.CONCLUSION: Our results demonstrate that EGCG interacts with TGFRⅡ and inhibits the expression of α-SMA via the TGF-β-Smad2/3 pathway in human lung fibroblast MRC-5 cells.展开更多
The present study was carried out to determine whether the consumption of epigallocatechin (EGCG), the major bioactive green tea catechin, exerts a positive effect on lowering in vivo lipid peroxidation, a measure of ...The present study was carried out to determine whether the consumption of epigallocatechin (EGCG), the major bioactive green tea catechin, exerts a positive effect on lowering in vivo lipid peroxidation, a measure of oxidative stress, in healthy postmenopausal women. Urinary excretion of secondary lipid peroxidation products, a measure of in vivo lipid peroxidation, was determined in 40 participants randomly assigned to consume a green tea catechin extract (843.0 ± 44.0 mg EGCG/d) or placebo capsules for 12 months. Urine samples were analyzed for individual polar and nonpolar lipophilic aldehydes and related carbonyl compounds by high-performance liquid chromatography (HPLC) at the beginning and at the end of the 12-month intervention period. Results show that two nonpolar aldehydes, nonanal and decatrienal, were both 48% lower (p in vivo antioxidant activity exists with long-term EGCG consumption, which could slightly limit oxidative damage associated with lipid peroxidation and the onset and progression of chronic diseases.展开更多
Background:𝛽-hemoglobinopathies are one of the most common recessive genetic diseases worldwide,with limited treatments available,particularly in developed countries where the prevalence is higher.Pharmacologi...Background:𝛽-hemoglobinopathies are one of the most common recessive genetic diseases worldwide,with limited treatments available,particularly in developed countries where the prevalence is higher.Pharmacological reactivation of Fetal Hemoglobin(HbF)is a promising therapeutic strategy.However,approximately 25%of the patients do not respond to Hydroxyurea(HU),the first and most commonly used HbF inducing agent approved by the FDA.Objective:Here,we performed an in vitro assessment of transcriptional effects induced by natural bioactive compounds,namely Epigallocatechin-3-gallate(EGCG)and genistein(GN)in globin genes(HBA1,HBB,HBG1 and HBG2)in HbF regulators/silencer genes(KLF1,BCL11A,MYB and BGLT3)and in epigenetic regulator genes(DNMT1,DNMT3A,DNMT3B,HDAC1,HDAC2,HDAC3 and HDAC8).Moreover,we evaluated EGCG’s in vivo effects in hematological parameters of healthy volunteers.Methods:K562 cells were exposed for 72 and 96 h to GN and EGCG at 100,250 and 500 ng/mL.Cell proliferation and viability were measured,and transcriptional levels were evaluated by qRT-PCR.For in vivo assay,complete blood count was determined by flow cytometry and HbF level was determined through HPLC in 30 healthy individuals before and after 225 mg EGCG ingestion per day during a 90-day period.Results:Both compounds impact cellular metabolism and proliferation with no cytotoxic effects.Divergent GN and EGCG effects in globin and BGLT3 expression levels suggest the involvement of divergent signaling pathways.As for the epigenetic potential,EGCG particularly affects HDAC2 and HDAC8 transcription,whereas GN signifi-cantly affects expression patterns of methylation and acetylation modulators.HU appears to have time divergent effects,with greater impact in methylation at 72 h(overregulates DNTM3A)while affecting acetylation mostly at 96 h(downregulates HDAC1 and HDAC8).Additionally,in vivo,EGCG demonstrated a modulator effect in hematopoiesis and HbF induction.Conclusion:Our results advocate EGCG and GN with HbF pharmacological reactivation potential and sustain further research as new alternative approaches for𝛽-hemoglobinopathies therapies.展开更多
Objective:Several studies have found that epigallocatechin-3-gallate(EGCG)can alleviate acute radiation-induced esophagitis,inhibit pulmonary inflammation and fibrosis,and reduce the severity of cardiovascular disease...Objective:Several studies have found that epigallocatechin-3-gallate(EGCG)can alleviate acute radiation-induced esophagitis,inhibit pulmonary inflammation and fibrosis,and reduce the severity of cardiovascular disease.Therefore,this study was aimed at exploring the influence of EGCG on late radiation toxicity in the heart,esophagus,and lungs among patients with locally advanced lung cancer.Methods:The patients were divided into an EGCG group and a control group,the groups received EGCG and symptomatic treatment,respectively.The Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme was used to determine the late toxicity scores.Tumor responses were evaluated by chest computed tomography(CT),based on the Response Evaluation Criteria in Solid Tumors version 1.1.Results:We retrospectively analyzed 74 patients treated at our hospital from September 2012 to September 2016(37 patients received EGCG and 37 received supportive treatment).The late toxicity scores of the EGCG group decreased compared to those of the control group.An obvious clinical significance was observed for the oral EGCG solution in the treatment and prevention of late cardiac,esophageal,and pulmonary toxicity.However,no significant difference was found(P>0.05).The tumor response rates were similar in the two groups.Moreover,there was no difference in progression-free survival(PFS)between the groups(P>0.05).Conclusion:Oral EGCG solution might alleviate radiation-induced late cardiac,esophageal,and pulmonary toxicity but has no significant effect on the tumor response rate and PFS following radiotherapy.展开更多
Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to...Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.展开更多
Breast cancer is the most common cancer among women. In recent years, many in vitro and in vivo studies indicate that green tea possesses anti-cancer effects. The epidemiological studies, however, have produced inconc...Breast cancer is the most common cancer among women. In recent years, many in vitro and in vivo studies indicate that green tea possesses anti-cancer effects. The epidemiological studies, however, have produced inconclusive results in humans. Likewise, results from animal models about the preventive or therapeutic effects of green tea components are inconclusive. The mechanisms by which green tea intake may influence the risk of breast cancer in humans remain elusive. Here, we review recent studies of green tea polyphenols and their applications in the prevention and treatment of breast cancer. Furthermore, we discuss the effect of green tea components on breast cancer by reviewing epidemiological studies, animal model studies and clinical trials. At last, we discuss the mechanisms by which green tea components suppress the develop-ment and recurrence of breast cancer. A better understanding of the mechanisms will improve the utilization of green tea in breast cancer prevention and therapy and pave the way to novel prevention and treatment strategies for breast cancer.展开更多
Functional foods,namely as natural or processed foods containing bioactive compounds,can provide health-promoting effects beyond basic nutrition,or offer the prevention or supplementary treatment of chronic diseases.T...Functional foods,namely as natural or processed foods containing bioactive compounds,can provide health-promoting effects beyond basic nutrition,or offer the prevention or supplementary treatment of chronic diseases.The bioactive components in functional foods usually have pleiotropic effects,including antioxidant,anti-inflammatory,hypolipidemic,glycemic-regulating,cytoprotective,and neuroprotective functions.Autophagy is one of the highly conserved cellular processes for the clearance of aberrant components in eukaryotic cells,and plays an essential role in health promotion and prevention and treatment of a series of chronic diseases.Once the cells are in the stress environment,the induced autophagy will accelerate the clearance of cellular damaged or toxic protein aggregates or dysfunctional cellular organelles to maintain homeostasis in cells.In this article,we summarize several widely investigated bioactive components used as functional foods,such as resveratrol,epigallocatechin-3-gallate,curcumin and trehalose,with the regulatory function for autophagy during the intervention of chronic diseases,which will provide the references or novel thoughts for the development of functional foods with the modulation of autophagy.展开更多
Damaged skin cannot prevent harmful bacteria from invading tissues,causing infected wounds or even severe tissue damage.In this study,we developed a controlled-release antibacterial composite hydrogel system that can ...Damaged skin cannot prevent harmful bacteria from invading tissues,causing infected wounds or even severe tissue damage.In this study,we developed a controlled-release antibacterial composite hydrogel system that can promote wound angiogenesis and inhibit inflammation by sustained releasing Cu-Epigallocatechin-3-gallate(Cu-EGCG)nano-capsules.The prepared SilMA/HAMA/Cu-EGCG hydrogel showed an obvious inhibitory effect on Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus).It could also promote the proliferation and migration of L929 fibroblasts.In vivo full-thickness infected wound healing experiments confirmed the angiogenesis and inflammation regulating effect.Accelerate collagen deposition and wound healing speed were also observed in the SilMA/HAMA/Cu-EGCG hydrogel treated group.The findings of this study show the great potential of this controlled-release antibacterial composite hydrogel in the application of chronic wound healing.展开更多
Objective To investigate excretion profiles of the four major anti-oxidant active catechins, (-) epigallo-catechin-3-gallate (EGCG), (-) epicatechin-3-gallate (ECG), (-) epigallocatechin (EGC), and epicatechin (EC) in...Objective To investigate excretion profiles of the four major anti-oxidant active catechins, (-) epigallo-catechin-3-gallate (EGCG), (-) epicatechin-3-gallate (ECG), (-) epigallocatechin (EGC), and epicatechin (EC) in tea polyphenols (TP) in rats in order to provide experimental data for clinical uses and development of TP as a novel drug. Methods The above four catechins in urine, bile, and feces were simultaneously determined by high performance liquid chromatography coupled with ultraviolet absorption detector (HPLC-UV) assay with a binary gradient elution. The samples were extracted by ethyl acetate prior to HPLC. The quantification was carried out by peak area internal standard method. Following iv dosing TP 100 mg/kg to rats, the samples were collected at different time intervals up to 8 h (urine and bile) and 24 h (feces). Results The urinary Ae, 0-8 h (cumulative excretion amount over 8 h) of EGCG, ECG, EGC, and EC were, on the average, 150.83, 30.75, 116.69, and 254.56 μg, corresponding to fe, 0-8 h (cumulative excretion fraction of dose over 8 h) of 1.45%, 0.84%, 7.88%, and 10.73%, respectively; the biliary Ae, 0-8 h were 12.61, 42.64, 6.61, and 1.24 μg, corresponding to the fe, 0-8 h of 0.12%, 1.16%, 0.45%, and 0.053%,respectively. For fecal excretion, only EGCG and EGC were detected with Ae, 0-24 h of 7.38 μg (fe, 0-24 h of 0.07%) and 157 μg (fe, 0-24 h of 9.99 %), respectively. The fe, total (the total fe of 3 excretory routes) were 18.32%, 10.78%, 2.00%, and 1.64% for EGC, EC, ECG, and EGCG, respectively. Conclusion EGCG and EC are mainly excreted in urine, ECG in bile, and EGC in feces by reference to their Ae and fe. The excretion of the four catechins based on fe, total is ranked in order of EGC > EC > ECG > EGCG. Only small amount of four catechins are recovered in urine, bile, and feces, indicating an extensive metabolic conversion of catechins in the rat body.展开更多
Myocardial infarction(MI)exhibits a complicated and ever-accelerated pathological change involving excessive reactive oxygen species(ROS)and the up-regulation of pro-inflammatory cytokines in the initial stage,and a p...Myocardial infarction(MI)exhibits a complicated and ever-accelerated pathological change involving excessive reactive oxygen species(ROS)and the up-regulation of pro-inflammatory cytokines in the initial stage,and a permanently inadequate blood supply.Herein,an injectable hydrogel fabricated by nanoparticles(NPs)knotted thiolated hyaluronic acid(HA-SH)was reported to reverse the hostile microenvironment and rebuild the heart functions after MI.Inspired by the composite shell-core structure of Ferrero chocolate sphere,a mimetic nanocarrier was designed to consist of the hydrophobic dimethyloxalylglycine(DMOG)NPs core and a thick polydopamine(PDA)shell formed by the self-polymerization of dopamine embedded with watersoluble drug epigallocatechin-3-gallate(EGCG)throughπ-πinteractions.The resulted"Ferrero-like"NPs exhibited a"three-inone"capacity,namely loading two distinct drugs,elimination of ROS,and serving a crosslinker to knot HA-SH."Ferrero-like"NPs and HA-SH could rapidly form a hydrogel that exhibited a stable mechanical property,high capability to capture ROS,and programmed release of EGCG and DMOG.Four weeks after deploying the"Ferrero-like"NPs knotted hydrogels into rat infarcted hearts,the ejection fraction(EF)increased by 23.7%,and the infarct size decreased by 21.1%,and the fibrotic area reduced by 24.4%.The outcomes of immunofluorescence staining and reverse transcription-polymerase chain reaction(RTPCR)demonstrated a down-regulation of inflammatory factors(tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)),up-regulation of vascular related growth factors(hypoxia inducible factor-1α(HIF-1α),vascular endothelial growth factor A(VEGFA),von Willebrand factor(vWF),angiopoietin-1(Ang-1))and cardiac-related m RNAs(gap junction protein(Cx43),Cadherin 2).All in all,in this report,a very simple approach to intertemporally address the intricate and ongoing pathological changes after MI by injecting"Ferrero-like"NPs knotted hydrogels is developed to reverse hostile microenvironment,with an ability to scavenge ROS,down-regulate pro-inflammation factors in the first stage,and promote angiogenesis in a long term,thereby contributing to a significant improvement of heart functions.展开更多
Metformin,a first-line drug for type 2 diabetes mellitus,has been recognized as a potential anti-tumor agent in recent years.Epigallocatechin-3-gallate(EGCG),as the dominant catechin in green tea,is another promising ...Metformin,a first-line drug for type 2 diabetes mellitus,has been recognized as a potential anti-tumor agent in recent years.Epigallocatechin-3-gallate(EGCG),as the dominant catechin in green tea,is another promising adjuvant agent for tumor prevention.In the present work,the potential effect of EGCG on the anti-tumor efficacy of metformin in a mouse melanoma cell line(B16F10)was investigated.Results indicated that EGCG and metformin exhibited a synergistic effect on cell viability,migration,and proliferation,as well as signal transducer and activator of transcription 3/nuclear factor-κB(STAT3/NF-κB)pathway signaling and the production of inflammation cytokines.Meanwhile,the combination showed an antagonistic effect on cell apoptosis and oxidative stress levels.The combination of EGCG and metformin also differentially affected the nucleus(synergism)and cytoplasm(antagonism)of B16F10 cells.Our findings provide new insight into the potential effects of EGCG on the anti-tumor efficacy of metformin in melanoma cells.展开更多
The unending morbidity and mortality that results from cancer,as well as adverse reactions due to chemotherapy and the enormous economic burden of treatment and hospitalization,advocates for the necessity of chemoprev...The unending morbidity and mortality that results from cancer,as well as adverse reactions due to chemotherapy and the enormous economic burden of treatment and hospitalization,advocates for the necessity of chemopreventive measures.Cancer chemoprevention refers to the use of agents capable of reversing,reducing,or slowing down the pathology of cancer at various stages.Fortunately,a few therapeutic drugs with relatively low toxicity(e.g.,tamoxifen,finasteride),and a sparse number of vaccines(hepatitis B,HPV),are used to prevent specific cancers.In the general population,however,therapeutic options for cancer prevention are not common.Nonetheless,it is generally agreed that diet affects the genesis of cancer,and phytochemicals have the capacity of functioning as cancer chemoprevention agents.This is supported by epidemiological studies and clearly documented with animal models designed to mimic human carcinogenesis.Additionally,some public health strategies,such as recommendations for greater consumption of fruits and vegetables,reflect the merits of cancer chemoprevention.Here,we focus on some well-established natural product cancer chemopreventive agents,including resveratrol(grapes),epigallocatechin-3-gallate(green tea),sulforaphane(cruciferous vegetables),anthocyanins(grapes and berries),curcumin(turmeric),silibinin(milk thistle),and lycopene(tomatoes).As aptly demonstrated by genomic analysis and other methods,the mechanistic underpinning is variable and complex.In addition,responses may be mediated through indirect mechanisms,such as interaction with the microbiome.Furthermore,ancillary applications of chemopreventive agents are worthy of consideration,such as management of sequelae induced by chemotherapy.Recognizing the loss of millions of cancer patients every year,it is obvious that negating malignant metastatic conditions remains of paramount importance.In meeting this objective,cancer chemoprevention offers great promise.展开更多
基金funded by the Universiti Tunku Abdul Rahman Research fund(IPSR/RMC/UTARRF/2019-C2/L08)。
文摘Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control,SHR control and SHR treated with EGCG(50 mg/kg/day)or losartan(10 mg/kg/day).The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 days.Acetylcholineinduced endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of treatment.The vascular levels of reactive oxygen species,nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate were also measured.Moreover,the expression of angiotensinⅡtype 1(AT_(1))receptor protein was determined.Results:The systolic blood pressure was significantly decreased in SHR treated with EGCG.The impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR group.EGCG also significantly increased the levels of nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate,while decreasing the level of reactive oxygen species and the protein expression of AT_(1)receptor in SHR.Conclusions:EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability,which may be modulated partly by inhibition of vascular AT_(1)receptors.An increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.
基金the National Natural Science Foundation of China(No.31800851).
文摘Alzheimer's disease(AD)shows cognitive impairments in clinic,which is multifactorial with different etiopathogenic mechanisms such as A|3 deposition,neuroinflammation and neuronal dystrophy involved.Therefore,multi-targets drugs with neuroprotective,anti-amyloidogenic and anti-inflammatory properties will be effective in AD treatment.Epigallocatechin-3-gallate(EGCG)possesses a broad spectrum of pharmacological activities in the prevention and treatment of multiple neurodegenerative diseases.In the present study,we showed that oral administration of EGCG(50 mg/kg)for 4 months significantly attenuated the cognitive deficits in APP/PS1 transgenic mice,which served as AD model.Moreover,EGCG induced an improvement in dendritic integrity and expression levels of synaptic proteins in the brain of APP/PS 1 mice.And EGCG exerted obvious anti-inflammatory effects,which was manifested by alleviating microglia activation,decreasing pro-inflammatory cytokine(IL-β)and increasing anti-inflammatory cytokines(IL-10,IL-β).Furthermore,p-amyloid(AP)plaques were markedly reduced in the hippocampus of 6-month old APP/PS 1 mice after EGCG treatment.In conclusion,these findings indicate that EGCG improves AD-like cognitive impairments through neuroprotective,anti-amyloidogenic and anti-inflammatory effects,thus is a promising therapeutic can didate for AD.
基金Supported by Public Technology Application Research Grant of Zhejiang Province(No.2011C33029)Natural Science Foundation of Zhejiang Province,China(No.LY13B020002)
文摘AIM:To investigate the mechanism underlying the anti-inflammatory effects of epigallocatechin-3-gallate(EGCG)in lipopolysaccharide(LPS)-stimulated human retinal endothelial cells(HRECs).METHODS:HRECspre-treatedwithEGCG(0-100μmol/L)were stimulated with LPS(250 ng/mL).Levels of tumor necrosis factor alpha(TNF-α),vascular endothelial growth factor(VEGF),monocyte chemotactic protein-1(MCP-1)and nitric oxide(NO)in the supernatants were determined by enzyme-linked immunosorbent assay(ELISA)and Griess assay.The protein expression of phosphorylated extracellular signal-regulated kinase(ERK)1/2 and p38 mitogen-activated protein kinases(p38)were determined by Western blot analysis.RESULTS:EGCG pre-treatment significantly inhibited the secretion of TNF-α,VEGF,MCP-1 and NO in LPSstimulated HRECs.Moreover,EGCG effectively attenuated LPS-induced activation and phosphorylation of ERK1/2 and p38 in HRECs in a dose-dependent manner.CONCLUSION:EGCG exhibited inhibitory effects on LPS-induced pro-inflammatory cytokines production by modulating ERK1/2 and p38 pathways in HRECs,suggesting EGCG as a potential candidate for antiinflammatory intervention.
文摘AIM: To investigate the(-)-epigallocatechin-3-gallate(EGCG) binding to transforming growth factor-β(TGF-β) type Ⅱ receptor(TGFRⅡ).METHODS: The expression of α-smooth muscle actin(α-SMA) was used as a marker for fibrotic change inhuman lung fibroblast MRC-5 cells. The α-SMA expression level was determined by western blotting and immunohistological analysis. We examined whether the anti-fibrotic effects of EGCG on MRC-5 cells was dependent on antioxidant mechanism by using edaravone and N-acetylcysteine(NAC). The suppression effects of EGCG on Smad2/3 activation were studied by confocal fluorescence microscopy. The binding of EGCG to recombinant TGFRⅡ protein was analyzed by immunoprecipitation and affinity chromatography.RESULTS: When MRC-5 cells were treated with TGF-β, EGCG decreased the expression of α-SMA in a dose dependent manner, whereas catechin did not influence the α-SMA expression in the cells. Except for EGCG, antioxidant compounds(e.g., edaravone and NAC) had no effects on the TGF-β-induced α-SMA expression. Nuclear localization of phosphorylated Smad2/3 was observed after TGF-β treatment; however, EGCG treatment attenuated the nuclear transportation of Smad2/3 in the presence or absence of TGF-β. After a TGFRⅡ expression vector was introduced into COS-7 cells, cell lysates were untreated or treated with EGCG or catechin. The immunoprecipitation experiments using the lysates showed that EGCG dose-dependently bound to TGFRⅡ and that catechin did not at all. Affinity chromatography study indicated that EGCG would bind to TGFRⅡ.CONCLUSION: Our results demonstrate that EGCG interacts with TGFRⅡ and inhibits the expression of α-SMA via the TGF-β-Smad2/3 pathway in human lung fibroblast MRC-5 cells.
文摘The present study was carried out to determine whether the consumption of epigallocatechin (EGCG), the major bioactive green tea catechin, exerts a positive effect on lowering in vivo lipid peroxidation, a measure of oxidative stress, in healthy postmenopausal women. Urinary excretion of secondary lipid peroxidation products, a measure of in vivo lipid peroxidation, was determined in 40 participants randomly assigned to consume a green tea catechin extract (843.0 ± 44.0 mg EGCG/d) or placebo capsules for 12 months. Urine samples were analyzed for individual polar and nonpolar lipophilic aldehydes and related carbonyl compounds by high-performance liquid chromatography (HPLC) at the beginning and at the end of the 12-month intervention period. Results show that two nonpolar aldehydes, nonanal and decatrienal, were both 48% lower (p in vivo antioxidant activity exists with long-term EGCG consumption, which could slightly limit oxidative damage associated with lipid peroxidation and the onset and progression of chronic diseases.
基金an IDI&CA grant IPL/2019/HemoFet_ESTeSL and by H&TRC-Health&Technology Re-search Center,ESTeSL-Escola Superior de Tecnologia da Saúde,Insti-tuto Politécnico de Lisboa.
文摘Background:𝛽-hemoglobinopathies are one of the most common recessive genetic diseases worldwide,with limited treatments available,particularly in developed countries where the prevalence is higher.Pharmacological reactivation of Fetal Hemoglobin(HbF)is a promising therapeutic strategy.However,approximately 25%of the patients do not respond to Hydroxyurea(HU),the first and most commonly used HbF inducing agent approved by the FDA.Objective:Here,we performed an in vitro assessment of transcriptional effects induced by natural bioactive compounds,namely Epigallocatechin-3-gallate(EGCG)and genistein(GN)in globin genes(HBA1,HBB,HBG1 and HBG2)in HbF regulators/silencer genes(KLF1,BCL11A,MYB and BGLT3)and in epigenetic regulator genes(DNMT1,DNMT3A,DNMT3B,HDAC1,HDAC2,HDAC3 and HDAC8).Moreover,we evaluated EGCG’s in vivo effects in hematological parameters of healthy volunteers.Methods:K562 cells were exposed for 72 and 96 h to GN and EGCG at 100,250 and 500 ng/mL.Cell proliferation and viability were measured,and transcriptional levels were evaluated by qRT-PCR.For in vivo assay,complete blood count was determined by flow cytometry and HbF level was determined through HPLC in 30 healthy individuals before and after 225 mg EGCG ingestion per day during a 90-day period.Results:Both compounds impact cellular metabolism and proliferation with no cytotoxic effects.Divergent GN and EGCG effects in globin and BGLT3 expression levels suggest the involvement of divergent signaling pathways.As for the epigenetic potential,EGCG particularly affects HDAC2 and HDAC8 transcription,whereas GN signifi-cantly affects expression patterns of methylation and acetylation modulators.HU appears to have time divergent effects,with greater impact in methylation at 72 h(overregulates DNTM3A)while affecting acetylation mostly at 96 h(downregulates HDAC1 and HDAC8).Additionally,in vivo,EGCG demonstrated a modulator effect in hematopoiesis and HbF induction.Conclusion:Our results advocate EGCG and GN with HbF pharmacological reactivation potential and sustain further research as new alternative approaches for𝛽-hemoglobinopathies therapies.
基金The authors declare that they have no competing interests.We thank the patients and their families who participated in this studyThis work was supported by the National Natural Science Foundation of China(Grant No.81502667)the Shandong Provincial Natural Science Foundation(ZR2016HM35).
文摘Objective:Several studies have found that epigallocatechin-3-gallate(EGCG)can alleviate acute radiation-induced esophagitis,inhibit pulmonary inflammation and fibrosis,and reduce the severity of cardiovascular disease.Therefore,this study was aimed at exploring the influence of EGCG on late radiation toxicity in the heart,esophagus,and lungs among patients with locally advanced lung cancer.Methods:The patients were divided into an EGCG group and a control group,the groups received EGCG and symptomatic treatment,respectively.The Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme was used to determine the late toxicity scores.Tumor responses were evaluated by chest computed tomography(CT),based on the Response Evaluation Criteria in Solid Tumors version 1.1.Results:We retrospectively analyzed 74 patients treated at our hospital from September 2012 to September 2016(37 patients received EGCG and 37 received supportive treatment).The late toxicity scores of the EGCG group decreased compared to those of the control group.An obvious clinical significance was observed for the oral EGCG solution in the treatment and prevention of late cardiac,esophageal,and pulmonary toxicity.However,no significant difference was found(P>0.05).The tumor response rates were similar in the two groups.Moreover,there was no difference in progression-free survival(PFS)between the groups(P>0.05).Conclusion:Oral EGCG solution might alleviate radiation-induced late cardiac,esophageal,and pulmonary toxicity but has no significant effect on the tumor response rate and PFS following radiotherapy.
文摘Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.
基金Supported by National Natural Science Foundation of China,No.81001587
文摘Breast cancer is the most common cancer among women. In recent years, many in vitro and in vivo studies indicate that green tea possesses anti-cancer effects. The epidemiological studies, however, have produced inconclusive results in humans. Likewise, results from animal models about the preventive or therapeutic effects of green tea components are inconclusive. The mechanisms by which green tea intake may influence the risk of breast cancer in humans remain elusive. Here, we review recent studies of green tea polyphenols and their applications in the prevention and treatment of breast cancer. Furthermore, we discuss the effect of green tea components on breast cancer by reviewing epidemiological studies, animal model studies and clinical trials. At last, we discuss the mechanisms by which green tea components suppress the develop-ment and recurrence of breast cancer. A better understanding of the mechanisms will improve the utilization of green tea in breast cancer prevention and therapy and pave the way to novel prevention and treatment strategies for breast cancer.
基金the National Natural Science Foundation of China(No.31571228 and No.31771318)Hubei Superior Discipline Groups of Physical Education and Health Promotion,and Outstanding Youth Scientific and Technological Innovation Team(T201624)Hubei Provincial Department of Education,as well as Chutian Scholar Program and Innovative Startup Foundation from Wuhan Sports University to Ning Chen.
文摘Functional foods,namely as natural or processed foods containing bioactive compounds,can provide health-promoting effects beyond basic nutrition,or offer the prevention or supplementary treatment of chronic diseases.The bioactive components in functional foods usually have pleiotropic effects,including antioxidant,anti-inflammatory,hypolipidemic,glycemic-regulating,cytoprotective,and neuroprotective functions.Autophagy is one of the highly conserved cellular processes for the clearance of aberrant components in eukaryotic cells,and plays an essential role in health promotion and prevention and treatment of a series of chronic diseases.Once the cells are in the stress environment,the induced autophagy will accelerate the clearance of cellular damaged or toxic protein aggregates or dysfunctional cellular organelles to maintain homeostasis in cells.In this article,we summarize several widely investigated bioactive components used as functional foods,such as resveratrol,epigallocatechin-3-gallate,curcumin and trehalose,with the regulatory function for autophagy during the intervention of chronic diseases,which will provide the references or novel thoughts for the development of functional foods with the modulation of autophagy.
基金funded by National Key Research and Development Program of China(2017YFA0105602,2018YFA0108700)NSFC Projects of INTERNATIONAL COOPERATION and Exchanges(81720108004)+6 种基金National Natural Science Foundation of China(81974019,82100275)Guangdong Provincial Special Support Program for Prominent Talents(2021JC06Y656)Science and Technology Planning Project of Guangdong Province(2020B1111170011,2022B1212010010)Guangdong special funds for science and technology innovation strategy,China(Stability support for scientific research institutions affiliated to Guangdong Province-GDCI 2021)Guangzhou Science and Technology Plan Project(202201000006)The Special Project of Dengfeng Program of Guangdong Provincial People’s Hospital(DFJH201812,KJ012019119,KJ012019423)The Marine Economy Development Project of Department of Natural Resources of Guangdong Province(No.GDNRC[2022]039).
文摘Damaged skin cannot prevent harmful bacteria from invading tissues,causing infected wounds or even severe tissue damage.In this study,we developed a controlled-release antibacterial composite hydrogel system that can promote wound angiogenesis and inhibit inflammation by sustained releasing Cu-Epigallocatechin-3-gallate(Cu-EGCG)nano-capsules.The prepared SilMA/HAMA/Cu-EGCG hydrogel showed an obvious inhibitory effect on Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus).It could also promote the proliferation and migration of L929 fibroblasts.In vivo full-thickness infected wound healing experiments confirmed the angiogenesis and inflammation regulating effect.Accelerate collagen deposition and wound healing speed were also observed in the SilMA/HAMA/Cu-EGCG hydrogel treated group.The findings of this study show the great potential of this controlled-release antibacterial composite hydrogel in the application of chronic wound healing.
基金support was provided by Dalian Municipal Fund of Science and Technology (2002B4NS044)Kangbosi Pharmaceutical Co. Ltd, China
文摘Objective To investigate excretion profiles of the four major anti-oxidant active catechins, (-) epigallo-catechin-3-gallate (EGCG), (-) epicatechin-3-gallate (ECG), (-) epigallocatechin (EGC), and epicatechin (EC) in tea polyphenols (TP) in rats in order to provide experimental data for clinical uses and development of TP as a novel drug. Methods The above four catechins in urine, bile, and feces were simultaneously determined by high performance liquid chromatography coupled with ultraviolet absorption detector (HPLC-UV) assay with a binary gradient elution. The samples were extracted by ethyl acetate prior to HPLC. The quantification was carried out by peak area internal standard method. Following iv dosing TP 100 mg/kg to rats, the samples were collected at different time intervals up to 8 h (urine and bile) and 24 h (feces). Results The urinary Ae, 0-8 h (cumulative excretion amount over 8 h) of EGCG, ECG, EGC, and EC were, on the average, 150.83, 30.75, 116.69, and 254.56 μg, corresponding to fe, 0-8 h (cumulative excretion fraction of dose over 8 h) of 1.45%, 0.84%, 7.88%, and 10.73%, respectively; the biliary Ae, 0-8 h were 12.61, 42.64, 6.61, and 1.24 μg, corresponding to the fe, 0-8 h of 0.12%, 1.16%, 0.45%, and 0.053%,respectively. For fecal excretion, only EGCG and EGC were detected with Ae, 0-24 h of 7.38 μg (fe, 0-24 h of 0.07%) and 157 μg (fe, 0-24 h of 9.99 %), respectively. The fe, total (the total fe of 3 excretory routes) were 18.32%, 10.78%, 2.00%, and 1.64% for EGC, EC, ECG, and EGCG, respectively. Conclusion EGCG and EC are mainly excreted in urine, ECG in bile, and EGC in feces by reference to their Ae and fe. The excretion of the four catechins based on fe, total is ranked in order of EGC > EC > ECG > EGCG. Only small amount of four catechins are recovered in urine, bile, and feces, indicating an extensive metabolic conversion of catechins in the rat body.
基金This work was supported by the Excellent Young Scientists Fund by National Natural Science Foundation of China(Grant No.31822020)the National Natural Science Foundation of China(Grant Nos.31771030&31870965)+1 种基金the National Key Research and Development Program of China(Grant No.2016YFC1101301)and Tianjin Outstanding Youth Science Foundation(Grant No.17JCJQJC46200).
文摘Myocardial infarction(MI)exhibits a complicated and ever-accelerated pathological change involving excessive reactive oxygen species(ROS)and the up-regulation of pro-inflammatory cytokines in the initial stage,and a permanently inadequate blood supply.Herein,an injectable hydrogel fabricated by nanoparticles(NPs)knotted thiolated hyaluronic acid(HA-SH)was reported to reverse the hostile microenvironment and rebuild the heart functions after MI.Inspired by the composite shell-core structure of Ferrero chocolate sphere,a mimetic nanocarrier was designed to consist of the hydrophobic dimethyloxalylglycine(DMOG)NPs core and a thick polydopamine(PDA)shell formed by the self-polymerization of dopamine embedded with watersoluble drug epigallocatechin-3-gallate(EGCG)throughπ-πinteractions.The resulted"Ferrero-like"NPs exhibited a"three-inone"capacity,namely loading two distinct drugs,elimination of ROS,and serving a crosslinker to knot HA-SH."Ferrero-like"NPs and HA-SH could rapidly form a hydrogel that exhibited a stable mechanical property,high capability to capture ROS,and programmed release of EGCG and DMOG.Four weeks after deploying the"Ferrero-like"NPs knotted hydrogels into rat infarcted hearts,the ejection fraction(EF)increased by 23.7%,and the infarct size decreased by 21.1%,and the fibrotic area reduced by 24.4%.The outcomes of immunofluorescence staining and reverse transcription-polymerase chain reaction(RTPCR)demonstrated a down-regulation of inflammatory factors(tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)),up-regulation of vascular related growth factors(hypoxia inducible factor-1α(HIF-1α),vascular endothelial growth factor A(VEGFA),von Willebrand factor(vWF),angiopoietin-1(Ang-1))and cardiac-related m RNAs(gap junction protein(Cx43),Cadherin 2).All in all,in this report,a very simple approach to intertemporally address the intricate and ongoing pathological changes after MI by injecting"Ferrero-like"NPs knotted hydrogels is developed to reverse hostile microenvironment,with an ability to scavenge ROS,down-regulate pro-inflammation factors in the first stage,and promote angiogenesis in a long term,thereby contributing to a significant improvement of heart functions.
基金the National Natural Science Foundation of China(No.U19A2034)。
文摘Metformin,a first-line drug for type 2 diabetes mellitus,has been recognized as a potential anti-tumor agent in recent years.Epigallocatechin-3-gallate(EGCG),as the dominant catechin in green tea,is another promising adjuvant agent for tumor prevention.In the present work,the potential effect of EGCG on the anti-tumor efficacy of metformin in a mouse melanoma cell line(B16F10)was investigated.Results indicated that EGCG and metformin exhibited a synergistic effect on cell viability,migration,and proliferation,as well as signal transducer and activator of transcription 3/nuclear factor-κB(STAT3/NF-κB)pathway signaling and the production of inflammation cytokines.Meanwhile,the combination showed an antagonistic effect on cell apoptosis and oxidative stress levels.The combination of EGCG and metformin also differentially affected the nucleus(synergism)and cytoplasm(antagonism)of B16F10 cells.Our findings provide new insight into the potential effects of EGCG on the anti-tumor efficacy of metformin in melanoma cells.
基金This work was supported in part by the California Table Grape Commission.
文摘The unending morbidity and mortality that results from cancer,as well as adverse reactions due to chemotherapy and the enormous economic burden of treatment and hospitalization,advocates for the necessity of chemopreventive measures.Cancer chemoprevention refers to the use of agents capable of reversing,reducing,or slowing down the pathology of cancer at various stages.Fortunately,a few therapeutic drugs with relatively low toxicity(e.g.,tamoxifen,finasteride),and a sparse number of vaccines(hepatitis B,HPV),are used to prevent specific cancers.In the general population,however,therapeutic options for cancer prevention are not common.Nonetheless,it is generally agreed that diet affects the genesis of cancer,and phytochemicals have the capacity of functioning as cancer chemoprevention agents.This is supported by epidemiological studies and clearly documented with animal models designed to mimic human carcinogenesis.Additionally,some public health strategies,such as recommendations for greater consumption of fruits and vegetables,reflect the merits of cancer chemoprevention.Here,we focus on some well-established natural product cancer chemopreventive agents,including resveratrol(grapes),epigallocatechin-3-gallate(green tea),sulforaphane(cruciferous vegetables),anthocyanins(grapes and berries),curcumin(turmeric),silibinin(milk thistle),and lycopene(tomatoes).As aptly demonstrated by genomic analysis and other methods,the mechanistic underpinning is variable and complex.In addition,responses may be mediated through indirect mechanisms,such as interaction with the microbiome.Furthermore,ancillary applications of chemopreventive agents are worthy of consideration,such as management of sequelae induced by chemotherapy.Recognizing the loss of millions of cancer patients every year,it is obvious that negating malignant metastatic conditions remains of paramount importance.In meeting this objective,cancer chemoprevention offers great promise.
