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epigallocatechin-3-gallate Alleviates Cognitive Deficits in APP/PS1 Mice

Current Medical Science 2020年第1期40卷 18-27页

作者： Jian BAO Wei LIU Hong-yan ZHOU Yu-ran GUI You-hua YANG Meng-juan WU Yi-fan XIAO Jin-ting SHANG Gui-feng LONG Xi-ji SHU Department of Pathology and Pathophysiology School of MedicineJianghan UniversityWuhan 430056China Department of Traditional Chinese Medicine School of MedicineJianghan UniversityWuhan 430056China Department of Physiology School of MedicineJianghan UniversityWuhan 430056China Institutes of Biomedical Sciences School of Medicinet Jianghan UniversityWuhan 430056China School of Life Science Jianghan UniversityWuhan 430056China

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 ***,multi-targets drugs with neuroprotective,anti-amyloidogenic and anti-inflammatory properties will be effective in AD ***-3-gallate(EGCG)possesses a broad spectrum of pharmacological activities in the prevention and treatment of multiple neurodegenerative *** 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 ***,EGCG induced an improvement in dendritic integrity and expression levels of synaptic proteins in the brain of APP/PS 1 *** 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 *** 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.

关键词： Alzheimer's disease cognitive impairments epigallocatechin-3-gallate anti・inflammation p-amyloid

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epigallocatechin-3-gallate exerts antihypertensive effects and improves endothelial function in spontaneously hypertensive rats

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Asian Pacific Journal of Tropical Biomedicine 2023年第7期13卷 287-295页

作者： Yucinda YY Khor Siew-Keah Lee Dharmani Devi M Wei Chih Ling Department of Pre-clinical Sciences M.Kandiah Faculty of Medicine and Health SciencesUniversiti Tunku Abdul RahmanSelangorMalaysia Department of Pharmacology Faculty of MedicineUniversiti MalayaKuala LumpurMalaysia

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 *** endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of *** vascular levels of reactive oxygen species,nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate were also ***,the expression of angiotensinⅡtype 1(AT_(1))receptor protein was ***:The systolic blood pressure was significantly decreased in SHR treated with *** impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR *** 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 ***: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)*** increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.

关键词： epigallocatechin-3-gallate Vascular protection Antihypertension Tetrahydrobiopterin Cyclic guanosine monophosphate Angiotensin typeⅠreceptor Spontaneously hypertensive rats

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epigallocatechin-3-gallate attenuates lipopolysaccharideinduced inflammation in human retinal endothelial cells

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International Journal of Ophthalmology(English edition) 2014年第3期7卷 408-412页

作者： Hui-Yan Zhang Jian-Yong Wang Hang-Ping Yao Hangzhou Vocational & Technical College Department of Ophthalmology the First Affiliated HospitalSchool of Medicine Zhejiang University State Key Laboratory for Diagnosis and Treatment of Infectious Diseases the First Affiliated Hospital School of Medicine Zhejiang University

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 *** protein expression of phosphorylated extracellular signal-regulated kinase(ERK)1/2 and p38 mitogen-activated protein kinases(p38)were determined by Western blot ***:EGCG pre-treatment significantly inhibited the secretion of TNF-α,VEGF,MCP-1 and NO in LPSstimulated ***,EGCG effectively attenuated LPS-induced activation and phosphorylation of ERK1/2 and p38 in HRECs in a dose-dependent ***: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.

关键词： epigallocatechin-3-gallate human retinal endothelial cells inflammatory factors

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epigallocatechin-3-gallate Modulates MicroRNA Expression Profiles in Human Nasopharyngeal Carcinoma CNE2 Cells

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Chinese Medical Journal 2017年第1期130卷 93-99页

作者： Bin-Bin Li Guo-Liang Huang Hua-Hui Li Xia Kong Zhi-Wei He Department of Pathophysiology Guangdong Medical University Dongguan Guangdong 523808 China Sino-American Cancer Research Institute Key Laboratory for Medical Diagnostics of Guangdong Province Guangdong Medical University Dongguan Guangdong 523808 China

Background： epigallocatechin-3-gallate （EGCG） has exhibited antitumor properties in several types of cancers, including nasopharyngeal carcinoma （NPC）, but the molecular mechanisms underlying this function remain incompletely understood. The aim of the present study was to characterize the global impact of EGCG on the expression of microRNAs （miRNAs） in NPC cells. Methods： Using microarray analysis, the alterations of miRNA expression profiles were investigated in EGCG-treated CNE2 cells. Furthermore, the target genes and signaling pathways regulated by EGCG-specific miRNAs were identified using target prediction program and gene ontology analysis. Results： A total of 14 miRNAs exhibited 〉2-fold expression changes in a dose-dependent manner after treatment with 20 μmol/L and 40 μmol/L EGCG. Totally 43, 49, and 52 target genes from these differentially expressed miRNAs were associated with the apoptosis, cell cycle regulation, and cell proliferation, respectively. A total of 66 signaling pathways, primarily involved in cancer development and lipid and glucose metabolism, were shown to be regulated by EGCG-specific miRNAs. Conclusion： EGCG induces considerable alterations of miRNA expression profiles in CNE2 cells, which provides mechanistic insights into cellular responses and antitumor activity mediated by EGCG.

关键词： Antitumor Agents epigallocatechin-3-gallate MicroRNAs Nasopharyngeal Carcinoma

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Cytotoxicity of epigallocatechin-3-gallate to LNCaP cellsin the presence of Cu^(2+)

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2005年第2期6卷 125-131页

作者：于海宁沈生荣熊耀康 Department of Tea Science Department of Pharmacology

epigallocatechin-3-gallate (EGCG) has shown remarkably anti-cancer activity, with its bioactivity being related to reactive conditions, such as pH and metal ions. The present study investigated the degradation of EGCG and its effect on prostate cancer cell in the presence of Cu2+. EGCG was incubated with prostate cancer cells, LNCaP, pretreated with or without Cu2+.EGCG in F-12 medium was quantified using HPLC and the viability of cells was assessed by gel electrophoresis, flow cytometry,and electron microscope. The results of HPLC showed that EGCG degraded completely within 12 h in F-12 medium with or without Cu2+. Gel electrophoresis and flow cytometry did not detect apoptosis of LNCaP cells when they were incubated with EGCG. Electron microscopy examination revealed that EGCG-Cu2+ complex led to damage of cytoplasm membrane in LNCaP cells. It was speculated that not EGCG, but its oxide and complex with Cu2+, are the bioactive components responsible for its cytotoxicity to LNCaP prostate cancer cells.

关键词： Copper epigallocatechin-3-gallate LNCaP cells Tea

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epigallocatechin-3-gallate induces apoptosis, inhibits proliferation and decreases invasion of glioma cell

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Neuroscience Bulletin 2014年第1期30卷 67-73页

作者： Hong Li Zhe Li Ya-Ming Xu Yue Wu Kang-Kang Yu Can Zhang Yong-Hua Ji Gang Ding Fu-Xue Chen School of Life Sciences Shanghai University Xinhua Hospital (Chongming) Affiliated to Shanghai Jiao Tong University Medical School Xinhua Translational Institute for Cancer Pain

epigallocatechin-3-gallate （EGCG）, a major polyphenol in green tea, has been considered a potential therapeutic and chemopreventive agent for cancer. Glioma is a malignant tumor with high mortality but effective therapy has not yet been developed. In this study, we found that EGCG induced apoptosis in U251 glioma cells via the laminin receptor （molecular weight 67kDa） in a time- and dose-dependent manner, decreased their invasiveness and inhibited their proliferation. The mitogen-activated protein kinase pathway was shown to be involved in glioma cell apoptosis and proliferation. Furthermore, the mRNA levels of matrix metalloproteinase （MMP）-2 and MMP-9 were reduced after EGCG treatment. These results suggest that EGCG has important therapeutic effects with low toxicity and side-effects, and could be used in cancer chemoprevention.

关键词： glioma epigallocatechin-3-gallate proliferation apoptosis invasion

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epigallocatechin-3-gallate suppresses transforming growth factor-beta signaling by interacting with the transforming growth factor-beta typeⅡreceptor

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World Journal of Experimental Medicine 2013年第4期3卷 100-107页

作者： Masaki Tabuchi Sumio Hayakawa Eiko Honda Kana Ooshima Tatsuki Itoh Koji Yoshida Ah-Mee Park Hideaki Higashino Mamoru Isemura Hiroshi Munakata Department of Biochemistry Kinki University Faculty of Medicine Division of Signaling in Cancer and Immunology Institute for Genetic Medicine Hokkaido University Life Science Research Institute Kinki University Department of Pharmacology Kinki University Faculty of Medicine Department of Pathology Kinki University Faculty of Medicine Graduate School of Nutritional and Environmental Sciences University of Shizuoka

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 ***: 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.

关键词： epigallocatechin-3-gallate Transforming growth factor-β Myofibroblast α-smooth muscle actin Fibrosis

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epigallocatechin-3-gallate addition to glass-ionomer cements:Influence on physical and antibacterial properties

Epigallocatechin-3-gallate addition to glass-ionomer cements...

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中华口腔医学会第14次全国口腔医学学术会议（2012年会）

作者： Jieqiong Hu Cui Huang School & Hospital of Stomatology(430072),Wuhan University,Wuhan,Hubei province.

Objectives:Glass-ionomer cements(GIC)was widely used as luting materials,cavity liners and bases,and restorative materials because of its biocompatible with low ***-3-gallate(EGCG)was the antimicrobial monomeric component of tea *** aim of this study was to evaluate the addition of EGCG to a conventional GIC on physical and antibacterial propertoes. Methods:A conventional GIC,Fuji IX,was used as control ***,dissolved in absolute ethyl alcohol(100 mg/ml),was incorporated into GIC at 0.1%(w/w)as experimental ***(CHX)powder was added into GIC at 1%(w/w) as positive *** strength was evaluated using a universal testing machine and surface microhardness was measured using Knoop microhardness tester. Streptococcus mutans UA 159 was cultured adherent to the surfaces of the specimens for both 4h and 24h,and were scanned by scanning electron microscopy(SEM).MTT assay,based on the reduction of a yellow tetrazolium salt to a purple formazan,was used to evaluate the biofilm adherent to the specimen *** separate-out antibacterial was evaluated by agar-diffusion *** were using ANOVA and Tukey’s test. Results:Compared with GIC group,there was a significant increase in the flexural strength for GIC-EGCG group(P0.05),but it’s significant increased compared with GIC-CHX group (P0.05).No inhibition zones detected in both GIC-EGCG and GIC group. Conclusions:These findings suggested that GIC-containing 0.1%(w/w)EGCG is a promising restorative material with improved mechanical properties and tendency of better direct contact antibacterial properties.

关键词： epigallocatechin-3-gallate glass-ionomer cements physical properties antibacterial properties biofilm

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Neuroprotective effect of epigallocatechin-3-gallate on hemisection-induced spinal cord injury in rats

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Neural Regeneration Research 2011年第6期6卷 405-411页

作者： Fengjun Deng Rubing Li Yingbao Yang Dan Zhou Qian Wang Jiangping Xu Department of Pharmaceutical Sciences Hunan Yiyang Medical College Yiyang 413000 Hunan Province China Pharmaceutical Preparation Section General Hospital of Guangzhou Military Command of PLA Guangzhou 510010 Guangdong Province China Department of Pharmacology School of Pharmaceutical Sciences Southern Medical University Guangzhou 510515 Guangdong Province China Pingxiang Healthy School Pingxiang 337000 Jiangxi Province China

epigallocatechin-3-gallate （EGCG）, a naturally occurring compound in green tea, has been widely used as an antioxidant agent. In the present study, model rats with acute spinal cord injury were intraperitoneally injected with 25, 50, and 100 mg/kg EGCG, and spinal cord ultrastructure, oxidative stress reaction, inflammatory factors, and apoptosis-associated gene expression were observed. Results showed that EGCG attenuated neuronal and axonal injury 24 hours post injury. It also decreased serum intedeukin-113, tumor necrosis factor-a, and intercellular adhesion molecule-1 release, and decreased apoptosis-associated gene expression. Furthermore, it increased the level of the superoxide anion （O2-）, superoxide dismutase, and B-cell lymphoma/leukemia-2, and reduced malondialdehyde levels. Furthermore, it reduced the expression of the pro-apoptotic protein Bax. Noticeably, EGCG at the 100 mg/kg dosage exhibited similar effects as methylprednisolone sodium succinate, which has been frequently used for clinical acute spinal cord injury. The results demonstrated that EGCG can significantly inhibit inflammation, suppress oxidation, and reduce apoptosis in acute spinal cord injury.

关键词： epigallocatechin-3-gallate spinal cord injury neuroprotective effect oxidative stress inflammation apoptosis

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Apoptotic effect of epigallocatechin-3-gallate on the human gastric cancer cell line MKN45 via activation of the mitochondrial pathway

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World Journal of Gastroenterology 2007年第31期13卷 4255-4259页

作者： Zhi-Hua Ran Qi xu Jin-Lu Tong Shu-Dong Xiao Departmentof Gastroenterology Renji Hospital Shanghai Jiao TongUniversity School of Medicine Shanghai Institute of DigestiveDisease Shanghai 200001 China

To investigate whether epigallocatechin-3-gallate （EGCG） can induce apoptosis of the gastric cancer cell line MKN45 and its apoptotic ***： To determine this, apoptotic rates of MKN45 cells after EGCG treatment with or without caspase-3 inhibitor were evaluated by Annexin V-FITC ＋ PI staining The influence of EGCG on the activity of caspase-3 in the MKN45 cells was determined by ELISA. By Rhodamine123 staining, the membrane potential change of the mitochondrion was also investigated, and mRNAs and protein expression of the bcl-2 family were analyzed by RT-PCR and Western ***： EGCG can induce apoptosis of MKN45 cells in time- and dose-dependent manner. Eight hours after EGCG treatment, the activity of caspase-3 in the MKN45 increased, especially 12 h after treatment. The mitochondrial membrane potential was significantly weakened 4 h after EGCG insult. The mRNA and protein expression levels of pro-apoptotic members, such as Bax, Bid and Bad, were upregulated gradually as treated time increased. Moreover, the mRNA and protein expression levels of anti-apoptotic members, such as Bcl-xL and Bcl-2, were inhibited. CONCLUSION： These data support that EGCG can induce apoptosis of the human gastric cancer cell line MKN45, and the effect is in a time- and dose-dependent manner. The apoptotic pathway triggered by EGCG in MKN45 is mitochondrial-dependent.

关键词： epigallocatechin-3-gallate Stomachneoplasms Bcl-2 Apoptosis

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