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ellagic acid induces apoptosis through inhibition of nuclear factor κB in pancreatic cancer cells

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World Journal of Gastroenterology 2008年第23期14卷 3672-3680页

作者： Mouad Edderkaoui Irina Odinokova Izumi Ohno Ilya Gukovsky Vay Liang W Go Stephen J Pandol Anna S Gukovskaya Department of Medicine Veterans Affairs Greater Los Angeles Healthcare System and University of CaliforniaLos Angeles CA 90073CaliforniaUnited States Institute of Theoretical and Experimental Biophysics Russian Academy of SciencesPushchinoMoscow Region 142290Russia

AIM： To determine the effect of ellagic acid on apoptosis and proliferation in pancreatic cancer cells and to determine the mechanism of the pro-survival effects of ellagic acid.METHODS： The effect of ellagic acid on apoptosis was assessed by measuring Phosphatidylserine externalization, caspase activity, mitochondrial membrane potential and DNA fragmentation; and proliferation by measuring DNA thymidine incorporation. Mitochondrial membrane potential was measured in permeabilized cells, and in isolated mitochondria. Nuclear factor κB （NF-κB） activity was measured by electromobility shift assay （EMSA）. RESULTS： We show that ellagic acid, a polyphenolic compound in fruits and berries, at concentrations 10 to 50 mmol/L stimulates apoptosis in human pancreatic adenocarcinoma cells. Further, ellagic acid decreases proliferation by up to 20-fold at 50 mmol/L. ellagic acid stimulates the mitochondrial pathway of apoptosis associated with mitochondrial depolarization, cytochrome C release, and the downstream caspase activation. ellagic acid does not directly affect mitochondria. ellagic acid dose-dependently decreased NF-κB binding activity. Furthermore, inhibition of NF-κB activity using IkB wild type plasmid prevented the effect of ellagic acid on apoptosis. CONCLUSION： Our data indicate that ellagic acid stimulates apoptosis through inhibition of the prosurvival transcription factor NF-κB.

关键词： ellagic acid Nuclear factor-κB Apoptosis Pancreatic cancer

ellagic acid in strawberry(Fragaria spp.):Biological,technological,stability,and human health aspects

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Food Quality and Safety 2017年第4期1卷 227-252页

作者： Selva Muthukumaran Carole Tranchant John Shi Xingqian Ye Sophia Jun Xue Department of Food Science and Post-Harvest Technology Institute of TechnologyHaramaya UniversityPost Box 138Dire DawaEthiopia School of Food Science Nutrition and Family StudiesFaculty of Health Sciences and Community ServicesUniversitéde MonctonMonctonNew Brunswick E1A 3E9Canada***Guelph Research and Development CenterAgriculture and Agri-Food Canada93 Stone Road WestGuelphOntario N1G 5C9Canada School of Biosystems Engineering and Food Science Zhejiang UniversityHangzhouChina

ellagic acid(EA)is one of the plant phenolics associated with human health *** derives from ellagitannins found in some nuts,seeds,and fruits,especially *** are considered a functional food and nutraceutical source,mainly because of their high concentration of EA and its *** review presents the current state of knowledge regarding EA,focusing on its content in strawberry plants,stability during processing and storage of strawberry-based foods,production methods,and relevance to human *** alternatives to acid-solvent extraction,fermentation-enzymatic bioprocesses hold great promises for more eco-efficient production of EA from plant *** fruits are generally rich in EA,with large variations depending on cultivar,growth conditions and maturity at *** EA contents are also reported in strawberry achenes and leaves,and in wild *** postharvest storage,processing and subsequent storage can influence EA *** low concentration in strawberry juice and wine can be increased by incorporating pre-treated *** recognition of strawberries as functional foods is substantiated by evidence of EA biological effects,including antioxidant,antiinflammatory,antidiabetic,cardioprotective,neuroprotective,and prebiotic *** health benefits attributed to EA-rich foods are thought to involve various protective mechanisms at the cellular *** EA is converted by the intestinal microbiota to urolithins,which are better absorbed than EA and may contribute significantly to the health effects attributed to EA-rich *** on the evidence available,strawberry EA shows strong promises for functional,nutraceutical,and pharmaceutical *** research should be directed at quantifying EA in different parts of the strawberry plant and in their byproducts;optimizing EA production from byproducts;understanding the biological actions of EA-derived metabolites in vivo,inc

关键词： Strawberry plant ellagic acid Processing Metabolism Bioacti

ellagic acid Enhances Antioxidant System Activity and Maintains the Quality of Strawberry Fruit during Storage

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Phyton-International Journal of Experimental Botany 2024年第1期93卷 15-28页

作者： Jian Chen Jing Zhang Gang Pan Dandan Huang Shuhua Zhu College of Chemistry and Material Science Shandong Agricultural UniversityTaian271018China Agriculture and Rural Bureau of Penglai District Yantai265699China Laiyang Inspection and Testing Center Yantai265299China

ellagic acid(EA)is a natural antioxidant,widely present in a lot of forms’soft fruits,nuts,and other plant tissues,and helpful for promoting human health;however,its protective effect on postharvest fruit and improving the quality index of postharvest fruit have rarely been *** this experiment,the strawberries were soaked in 0,100,200,300,400,and 500 mg L^(−1) EA,respectively,and the influential EA on fruit quality and the antioxidant system of strawberries were *** with the control,EA treatment can reduce the browning degree and rotting rate of strawberry fruit during storage and augment the soluble solid content(SSC).EA treatment can also increase the content of related stuff and enzyme activity in antioxidant systems;the gene expression level of polyphenol oxidase(PPO)in strawberries treated with EA was always down-regulated,correspondingly,the expression of other antioxidant enzyme genes was *** the strawberry fruits treated with EA of different concentrations,300 mg L^(−1) EA had the best effect in the process of strawberry *** results suggested that the proper concentration of exogenous EA at 300 mg L−1 could maintain strawberries’quality and enhance the antioxidant system by improving the activities of antioxidative enzymes and the ascorbateglutathione(AsA-GSH)cycle during storage.

关键词： Strawberry ellagic acid antioxidative enzyme AsA-GSH cycle storage

ellagic acid inhibits gastric cancer cells by modulating oxidative stress and inducing apoptosis

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Asian Pacific Journal of Tropical Biomedicine 2024年第4期14卷 162-169页

作者： Jian Zheng Chun-Feng Li Department of Diagnostic Radiology Division Harbin Medical University Cancer HospitalHeilongjiangChina Department of Gastrointestinal Surgical Ward Harbin Medical University Cancer HospitalHeilongjiangChina

Objective:To evaluate the anticancer effect of ellagic acid on gastric cancer ***:MTT assay was used to evaluate the effect of ellagic acid at different concentrations(0.5-100μg/mL)on gastric cancer AGS ***-qPCR and Western blot analyses were applied to assess apoptosis(BCL-2,CASP-3,and BAX)and autophagy(LC3,ATG5,and BECN1)in AGS cells treated with ellagic *** expression of invasion-related markers including TP53,CDKN2A,and PTEN was *** addition,cell cycle markers including cyclin A,B,D,and E were measured by *** stress markers were evaluated using ***:ellagic acid inhibited the proliferation of AGS cells in a concentration-and time-dependent *** expression of BCL-2 was significantly decreased(Pellagic ***,this compound induced no significant changes in the expression levels of LC3,ATG5,and BECN1(P>0.05).Moreover,the oxidative stress markers including SOD,TAC,and MDA were increased by ellagic acid(Pellagic acid can inhibit cell proliferation,induce apoptosis,and modulate oxidative stress in AGS ***,further in vivo and molecular studies are needed to verify its anticancer efficacy.

关键词： ellagic acid Gastric cancer Apoptosis Autophagy Metastasis Proliferation

ellagic acid-induced Hypercoagulable State in Animals:a Potentially Useful Animal Hypercoagulable Model for Evaluation of Anticoagulants

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Chinese Medical Sciences Journal 2010年第4期25卷 237-242页

作者： Na Liu Jun-tian Liu Qiang-zong Zhang Department of Pharmacology Xi＇an Jiaotong University School of Medicine Xi＇an 710061 China

Objective To establish and evaluate a hypercoagulable animal model for the assessment of anticoagulants. Methods Forty mice, thirty-two rats, and twenty-four rabbits were randomly and equally divided into control group (saline) and three ellagic acid (EA)-treated groups (low, middle, and high doses). In the mice, bleeding time (BT) was estimated with tail transaction, and clotting time (CT) with template method. Prothrombin time (PT) and the activated partial thromboplastin time (APTT) in rats and rabbits were measured by means of Quick's one-stage assay and modified APTT assay respectively. In addition, thrombin activity was estimated in rats with PT assay using a hemagglutination analyzer. The circulating platelet aggregates were de- tected in rabbits through platelet counting and presented as the circulating platelet aggregate ratio (CPAR). Results EA shortened BT and CT in mice, PT and APTT in rats, and increased thrombin activity and CPAR, all in a dose-dependent manner. EA also brought reduction of PT and APTT in rabbits in dose- and time-dependent manners. Conclusion EA could induce hypercoagulable state through activating coagulation system and platelets in mice, rats, and rabbits.

关键词： ellagic acid hypercoagulable state coagulation platelet aggregation

Dietary ellagic acid supplementation attenuates intestinal damage and oxidative stress by regulating gut microbiota in weanling piglets

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Animal Nutrition 2022年第4期11卷 322-333页

作者： Wenxia Qin Baoyang Xu Yuwen Chen Wenbo Yang Yunzheng Xu Juncheng Huang Ting Duo Yihua Mao Guozong Zhou Xianghua Yan Libao Ma State Key Laboratory of Agricultural Microbiology College of Animal Sciences and TechnologyHuazhong Agricultural UniversityWuhanChina The Cooperative Innovation Center for Sustainable Pig Production WuhanChina Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology WuhanChina Wuhan Huayang Animal Pharmaceutical Co. Ltd WuhanChina Hubei Tianxin Biotech Co. LtdShiyanChina

Intestinal oxidative stress triggers gut microbiota dysbiosis,which is involved in the etiology of postweaning diarrhea and enteric *** acid(EA)can potentially serve as an antioxidant supplement to facilitate weaning transition by improving intestinal oxidative stress and gut microbiota ***,we aimed to investigate the effects of dietary EA supplementation on the attenuation of intestinal damage,oxidative stress,and dysbiosis of gut microbiota in weanling piglets.A total of126 piglets were randomly assigned into 3 groups and treated with a basal diet and 2 m L saline orally(Ctrl group),or the basal diet supplemented with 0.1%EA and 2 m L saline orally(EA group),or the basal diet and 2 m L fecal microbiota suspension from the EA group orally(FEA group),respectively,for 14 *** with the Ctrl group,EA group improved growth performance by increasing average daily feed intake and average daily weight gain(Pacids(P<0.05).Correspondingly,FEA group gained effects comparable to those of EA group on growth performance,intestinal damage,and intestinal antioxidant *** addition,the relative abundance of bacteria shifted in EA and FEA groups was significantly related to the examined indices(P<0.05).Overall,dietary EA supplemen

关键词： ellagic acid Gut microbiota Weanling piglets Intestinal damage Oxidative stress

Dietary ellagic acid ameliorated Clostridium perfringens-induced subclinical necrotic enteritis in broilers via regulating inflammation and cecal microbiota

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Journal of Animal Science and Biotechnology 2022年第5期13卷 1513-1530页

作者： Yu Tang Xinyue Zhang Yanan Wang Yongpeng Guo Peiqi Zhu Guiguan Li Jianyun Zhang Qiugang Ma Lihong Zhao State Key Laboratory of Animal Nutrition Poultry Nutrition and Feed Technology Innovation TeamCollege of Animal Science and TechnologyChina Agricultural UniversityNo.2.West Road Yuanming yuanBeijing 100193People’s Republic of China Jiangsu Lihua animal husbandry Co. Ltd.No.500Hexi VillageLuxi Village CommitteeNiutang TownWujin DistrictChangzhou CityJiangsu Province 213168People’s Republic of China COFCO feed Co. Ltd4th FloorNo.6Nandaan HutongXicheng DistrictBeijing 100193People’s Republic of China

Background: Subclinical necrotic enteritis(SNE), a common intestinal disease of broiler caused by Clostridium perfringens, could reduce production performance of broilers by chronic intestinal damage and poor absorption of nutrients. ellagic acid(EA) has been reported to present antioxidant and anti-inflammatory properties on human and animals in many aspects. This study was conducted to evaluate the effect and mechanism of EA in relieving SNE in broilers induced by C. ***: C. perfringens challenge decreased body weight(BW), average daily gain(ADG), jejunal villi height/crypt depth(V/C) ratio, the activity of catalase(CAT) and the mRNA expression of zonula occludens 1(ZO-1) in jejunal mucosa of broilers. While feed conversion ratios(FCR), jejunal crypt depth(CD), the activities of myeloperoxidase(MPO) and diamine oxidase(DAO), as well as the concentrations of interleukin 6(IL-6), C-reactive protein(CRP) and procalcitonin(PCT) in serum, the activities of inducible nitric oxide synthase(iNOS) and lysozyme(LZM), the concentration of malondialdehyde(MDA), and the mRNA expressions of claudin-2, TNF-α, IL-1β, TLR-4, TLR-2, NF-κB,JAK3, STAT6 and iNOS in jejunal mucosa of broilers were increased by C. perfringens challenge. Dietary EA supplement relieved these adverse effects, and heightened jejunal villi height(VH), the concentration of D-xylose in plasma, activity of superoxide dismutase(SOD), and the mRNA expression of occludin in jejunal mucosa of *** alpha diversity of cecal microbiota indicated that dietary EA supplement increased observed species and Shannon index. C. perfringens challenge increased the relative abundance of Firmicutes and decreased the relative abundance of Desulfobacterota in cecal microbiota. EA increased the relative abundance of Firmicutes in cecal microbiota. LEfSe analysis showed that C. perfringens challenge triggered the imbalance of cecal microbiota in broilers, dietary EA supplementation led to a small beneficial e

关键词： Broiler Clostridium perfringens ellagic acid Intestinal microbiota Subclinical necrotic enteritis

In vitro and in vivo antioxidant activities of three major polyphenolic compounds in pomegranate peel: ellagic acid, punicalin, and punicalagin

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Journal of Integrative Agriculture 2017年第8期16卷 1808-1818页

作者： SUN Yu-qing TAO Xin MEN Xiao-ming XU Zi-wei WANG Tian College of Animal Science & Technology Nanjing Agricultural University Institute of Animal Husbandry and Veterinary Science Zhejiang Academy of Agricultural Sciences

Pomegranates is abundant in polyphenols and is well-known for its antioxidant activity. Punicalagin （PG） is a major poly- phenolic compound in the pomegranate peel. In certain conditions, PG can be hydrolyzed to punicallin （PL） and ellagic acid （EA）, and PL can be further hydrolyzed to EA. PG, PL, and EA all play important roles in the antioxidant activity of pomegranate peels. This study was conducted to compare the in vitro antioxidant activity and in vivo anti-oxidative stress effects of PG, PL, and EA. For the in vitro test, 2,2-diphenyl-l-picrylhydrazyl radical （DPPH.） and superoxide anion （O2~） scavenging capacities, ferric-reducing antioxidant power （FRAP）, and lipid peroxidation （LPO） inhibition capacities of PG, PL, and EA were tested. For the in vivo test, oxidatively stressed mice, which were induced by oxidized fish oil, were administrated PG, PL or EA （10 mg kg-1 d-1） for 21 days. The results showed that the in vitro antioxidant activity trends were EA〉PG〉PL〉Trolox in scavenging DPPH., PG〉PL〉EA=Trolox in scavenging O2~, EA〉PG=PL〉Trolox in FRAP, and Trolox〉PG〉EA〉PL in LPO inhibition. In the in vivo test, the EAt＇reatment increased the average daily weight gain and total antioxidant capacity （T-AOC） in the plasma （P〈0.05）, liver （P〈0.05）, and intestine （P〈0.05） in oxidatively stressed mice. It increased the superoxide dismutase （SOD） activity in the liver （P〈0.05） and intestine （P〈0.05）. It increased the glutathi- one peroxidase （GSH-Px） activity in the intestine （P〈0.05） and the intestinal villus height to crypt depth ratio （P〈0.05）. EA treatment decreased the malondialdehyde （MDA） content in the plasma （P〈0.05）, liver （P〈0.05）, and intestine （P〈0.05） and the mRNA expressions of the pro-inflammatory factors, TNF-a （P〈0.05）, IFN-y （P〈0.05） and IL-6 （P〈0.05）. PL increased the SOD （P〈0.05） and GSH-Px activities （P〈0.05） in the intestine and decreased the MDA content （P〈0.05） and the mRNA expressions of TNF-a （P〈0.05） and IL-6 （P〈0.05） in the intestine. PG i

关键词： ellagic acid punicalin punicalagin antioxidant oxidative stress

Effects of Season, Variety, and Processing Method on ellagic acid Content in Pomegranate Leaves

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Tsinghua Science and Technology 2008年第4期13卷 460-465页

作者：向兰邢东明雷帆王伟徐丽珍聂磊杜力军 Department of Biological Sciences and Biotechnology Tsinghua University Beijing 100084 China School of Pharmacy Shandong University Jinan 250012 China Department of Biological Sciences and Biotechnology Tsinghua University Beijing 100084 China Chinese Academy of Medicinal Science and Peking Union Medical College Beijing 100094 China School of Pharmacy Shandong University Jinan 250012 China

ellagic acid （EA） has aroused great interest worldwide owing to its antioxidant, anti-inflammatory, and anticarcinogenetic properties. The EA content in pomegranate leaf was measured in this study using high performance liquid chromatography to investigate the effects of season, variety, and processing method on the EA level. The results show that the EA content in 11 varieties of pomegranate from the Zaozhuang region in China range from 1.30 mg · g^-1 to 6.46 mg · g^-1 of dry weight in five consecutive seasons from June to October. An analysis of variance （ANOVA） shows that the EA content is significantly dependent on the season （p〈0.05）. The EA content increases significantly during the growing season to the highest level in September and October. The effect of the leaf variety on the EA content is less significant than the season. The processing methods have different effects on the EA content. Soaking for 24 hours slightly increases the EA content （p〈0.05）. Heating at 80℃ or 100℃ for 1 h after soaking has little influence on the EA content, while slow-fired cooking at high temperature significantly elevates the EA content （p〈0.05）. To improve quality and stability, several parameters such as leaf collection time, slow-fired cooking, and cooking time should be strictly controlled during the processing of pomegranate leaf tea and its extract.

关键词： pomegranate leaf ellagic acid effect of season variety processing method high performance liquid chromatography (HPLC)