Full Text:   <798>

Summary:  <987>

Suppl. Mater.: 

CLC number: 

On-line Access: 2021-05-07

Received: 2020-11-23

Revision Accepted: 2021-01-18

Crosschecked: 0000-00-00

Cited: 0

Clicked: 2493

Citations:  Bibtex RefMan EndNote GB/T7714




-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.5 P.397-409


Phenolic profile of jujube fruit subjected to gut microbiota fermentation and its antioxidant potential against ethyl carbamate-induced oxidative damage

Author(s):  Tao BAO, Ming ZHANG, Yuanqing ZHOU, Wei CHEN

Affiliation(s):  Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou 310058, China; more

Corresponding email(s):   zjuchenwei@zju.edu.cn

Key Words:  Jujube, Gut microbiota fermentation, Polyphenols, Ethyl carbamate, Antioxidant activity

Tao BAO, Ming ZHANG, Yuanqing ZHOU, Wei CHEN. Phenolic profile of jujube fruit subjected to gut microbiota fermentation and its antioxidant potential against ethyl carbamate-induced oxidative damage[J]. Journal of Zhejiang University Science B, 2021, 22(5): 397-409.

@article{title="Phenolic profile of jujube fruit subjected to gut microbiota fermentation and its antioxidant potential against ethyl carbamate-induced oxidative damage",
author="Tao BAO, Ming ZHANG, Yuanqing ZHOU, Wei CHEN",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Phenolic profile of jujube fruit subjected to gut microbiota fermentation and its antioxidant potential against ethyl carbamate-induced oxidative damage
%A Tao BAO
%A Yuanqing ZHOU
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 5
%P 397-409
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000754

T1 - Phenolic profile of jujube fruit subjected to gut microbiota fermentation and its antioxidant potential against ethyl carbamate-induced oxidative damage
A1 - Tao BAO
A1 - Ming ZHANG
A1 - Yuanqing ZHOU
A1 - Wei CHEN
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 5
SP - 397
EP - 409
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000754

ObjectiveTo evaluate the composition of bioactive substances and the antioxidant effects of jujube fruit under gut microbiota fermentation (GMF), and the inhibitory effect on cytotoxicity caused by ethyl carbamate (EC).
MethodsChanges in the contents of flavonoids, polyphenols, total sugars, and reducing sugars of jujube fruit after GMF (0, 2, 6, 12, 24, and 48 h) were determined. The oxidation resistance of fermented jujube fruits (from 0 to 48 h fermentation) was evaluated using in vitro 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) and ferric reducing antioxidant power (FRAP) assays. Inhibitory effects of 48 h-fermented jujube fruit at various concentrations (0.25, 0.50, 1.00, and 2.00 mg/mL) on EC-treated toxicity and DNA damage of Caco-2 cells were estimated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and nuclear staining assays, respectively. Effects of different concentrations of jujube fruit on EC-treated Caco-2 cells’ intracellular reactive oxygen species (ROS), glutathione (GSH) levels, and mitochondrial membrane potential (MMP) were also evaluated.
Resultsjujube fruit has rich bioactive components after GMF and shows strong antioxidant capacity. Fermented jujube fruit can inhibit the cytotoxicity and DNA damage of Caco-2 cells caused by EC and reduce intracellular ROS generation, as well as restoring GSH and MMP.
ConclusionsFermented jujube fruit extracts produced by GMF still contain biologically active substances which retain biological activity and antioxidation capabilities.


方法:红枣模拟肠道菌群酵解(0~48 h)后,采用比色法和高效液相色谱法分析黄酮、多酚、总糖和还原糖在发酵过程中的含量变化;采用体外抗氧化活性评价方法研究红枣发酵代谢产物抗氧化活性;采用MTT法和Hoechst 33258荧光探针研究不同浓度(0.25、0.50、1.00和2.00 mg/mL)红枣发酵48 h代谢产物对氨基甲酸乙酯诱导Caco-2细胞的细胞活力和DNA损伤的影响;分别采用6-羧基-2’,7’-二氯二氢荧光素二乙酸酯(DCFH-DA)和萘-2,3-二甲醛(NDA)荧光探针检测不同浓度(0.25、0.50和1.00 mg/mL)红枣发酵48 h代谢产物对氨基甲酸乙酯诱导Caco-2细胞内活性氧(ROS)和谷胱甘肽(GSH)水平;采用RH123荧光探针检测不同浓度(0.25、0.50和1.00 mg/mL)红枣发酵48h代谢产物对氨基甲酸乙酯诱导Caco-2细胞内线粒体膜电位的影响。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]AOAC, 1995. Official Methods of Analysis, 16th Ed. Association of Official Analytical Chemists, Arlington, USA.

[2]BansalA, SimonMC, 2018. Glutathione metabolism in cancer progression and treatment resistance. J Cell Biol, 217(7):2291-2298.

[3]BaoT, LiYT, XieJH, et al., 2018. Systematic evaluation of bioactive components and antioxidant capacity of some new and common bayberry cultivars using an in vitro gastrointestinal digestion method. Food Res Int, 103:326-334.

[4]BaoT, LiYT, XieJH, et al., 2019. Systematic evaluation of polyphenols composition and antioxidant activity of mulberry cultivars subjected to gastrointestinal digestion and gut microbiota fermentation. J Funct Foods, 58:338-349.

[5]BaoT, HaoX, ShishirMRI, et al., 2021. Cold plasma: an emerging pretreatment technology for the drying of jujube slices. Food Chem, 337:127783.

[6]CadenasS, 2018. Mitochondrial uncoupling, ROS generation and cardioprotection. Biochim Biophys Acta Bioenerg, 1859(9):940-950.

[7]CaoH, OuJY, ChenL, et al., 2019. Dietary polyphenols and type 2 diabetes: human study and clinical trial. Crit Rev Food Sci Nutr, 59(20):3371-3379.

[8]CardonaF, Andrés-LacuevaC, TulipaniS, et al., 2013. Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem, 24(8):1415-1422.

[9]ChangCC, YangMH, WenHM, et al., 2002. Estimation of total flavonoid content in propolis by two complementary colorimetric methods. J Food Drug Anal, 10(3):178-182.

[10]ChenJP, LiZG, MaiwulanjiangM, et al., 2013. Chemical and biological assessment of Ziziphus jujuba fruits from China: different geographical sources and developmental stages. J Agric Food Chem, 61(30):7315-7324.

[11]ChenW, FengLN, ShenY, et al., 2013. Myricitrin inhibits acrylamide-mediated cytotoxicity in human Caco-2 cells by preventing oxidative stress. Biomed Res Int, 2013:724183.

[12]ChenW, ShenY, SuHM, et al., 2014. Hispidin derived from Phellinus linteus affords protection against acrylamide-induced oxidative stress in Caco-2 cells. Chem Biol Interact, 219:83-89.

[13]ChenW, SuHM, XuY, et al., 2016a. Protective effect of wild raspberry (Rubus hirsutus Thunb.) extract against acrylamide-induced oxidative damage is potentiated after simulated gastrointestinal digestion. Food Chem, 196:943-952.

[14]ChenW, XuY, ZhangLX, et al., 2016b. Blackberry subjected to in vitro gastrointestinal digestion affords protection against ethyl carbamate-induced cytotoxicity. Food Chem, 212:620-627.

[15]ChenW, SuHM, XuY, et al., 2017. In vitro gastrointestinal digestion promotes the protective effect of blackberry extract against acrylamide-induced oxidative stress. Sci Rep, 7:40514.

[16]ChoiSH, AhnJB, KozukueN, et al., 2011. Distribution of free amino acids, flavonoids, total phenolics, and antioxidative activities of jujube (Ziziphus jujuba) fruits and seeds harvested from plants grown in Korea. J Agric Food Chem, 59(12):6594-6604.

[17]ChunSH, ChaYN, KimC, 2013. Urethane increases reactive oxygen species and activates extracellular signal-regulated kinase in RAW 264.7 macrophages and A549 lung epithelial cells. Arch Pharm Res, 36(6):775-782.

[18]ColomboNBR, RangelMP, MartinsV, et al., 2015. Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis. Braz J Med Biol Res, 48(9):852-862.

[19]CremoniniE, FragaCG, OteizaPI, 2019. (-)-Epicatechin in the control of glucose homeostasis: involvement of redox-regulated mechanisms. Free Radic Biol Med, 130:478-488.

[20]CuiX, WangJY, QiuNN, et al., 2016. In vitro toxicological evaluation of ethyl carbamate in human HepG2 cells. Toxicol Res (Camb), 5(2):697-702.

[21]DindaB, DindaM, RoyA, et al., 2020. Dietary plant flavonoids in prevention of obesity and diabetes. Adv Protein Chem Struct Biol, 120:159-235.

[22]DuLJ, GaoQH, JiXL, et al., 2013. Comparison of flavonoids, acidsphenolic, and antioxidant activity of explosion-puffed and sun-dried jujubes (Ziziphus jujuba Mill.). J Agric Food Chem, 61(48):11840-11847.

[23]DudonnéS, VitracX, CoutièreP, et al., 2009. Comparative study of antioxidant properties and total phenolic content of 30 plant extracts of industrial interest using DPPH, ABTS, FRAP, SOD, and ORAC assays. J Agric Food Chem, 57(5):1768-1774.

[24]FieldKJ, LangCM, 1988. Hazards of urethane (ethyl carbamate): a review of the literature. Lab Anim, 22(3):255-262.

[25]FragaCG, CroftKD, KennedyDO, et al., 2019. The effects of polyphenols and other bioactives on human health. Food Funct, 10(2):514-528.

[26]GaoQH, WuCS, WangM, 2013. The jujube (Ziziphus jujuba Mill.) fruit: a review of current knowledge of fruit composition and health benefits. J Agric Food Chem, 61(14):3351-3363.

[27]GowdV, BaoT, WangLL, et al., 2018. Antioxidant and antidiabetic activity of blackberry after gastrointestinal digestion and human gut microbiota fermentation. Food Chem, 269:618-627.

[28]GowdV, BaoT, ChenW, 2019. Antioxidant potential and phenolic profile of blackberry anthocyanin extract followed by human gut microbiota fermentation. Food Res Int, 120:523-533.

[29]GuCH, HowellK, DunsheaFR, et al., 2019. LC-ESI-QTOF/MS characterisation of phenolic acids and flavonoids in polyphenol-rich fruits and vegetables and their potential antioxidant activities. Antioxidants (Basel), 8(9):405.

[30]GuoS, DuanJA, TangYP, et al., 2009. High-performance liquid chromatography—two wavelength detection of triterpenoid acids from the fruits of Ziziphus jujuba containing various cultivars in different regions and classification using chemometric analysis. J Pharm Biomed Anal, 49(5):1296-1302.

[31]HuDW, XuY, XieJH, et al., 2018. Systematic evaluation of phenolic compounds and protective capacity of a new mulberry cultivar J33 against palmitic acid-induced lipotoxicity using a simulated digestion method. Food Chem, 258:43-50.

[32]HuangJ, ZhangCM, ZhaoX, et al., 2016. The jujube genome provides insights into genome evolution and the domestication of sweetness/acidity taste in fruit trees. PLoS Genet, 12(12):e1006433.

[33]HuangWZ, WangYJ, JiangXY, et al., 2017. Protective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao against acetaminophen-induced liver injury by inhibiting oxidative stress and inflammation in mice. Molecules, 22(10):1781.

[34]JiXL, HouCY, GaoYG, et al., 2020. Metagenomic analysis of gut microbiota modulatory effects of jujube (Ziziphus jujuba Mill.) polysaccharides in a colorectal cancer mouse model. Food Funct, 11(1):163-173.

[35]KawabataK, YoshiokaY, TeraoJ, 2019. Role of intestinal microbiota in the bioavailability and physiological functions of dietary polyphenols. Molecules, 24(2):370.

[36]KimYJ, SohnE, KimJH, et al., 2020. Catechol-type flavonoids from the branches of Elaeagnus glabra f. oxyphylla exert antioxidant activity and an inhibitory effect on amyloid-β aggregation. Molecules, 25(21):4917.

[37]KouLF, SunR, JiangXY, et al., 2020. Tumor microenvironment-responsive, multistaged liposome induces apoptosis and ferroptosis by amplifying oxidative stress for enhanced cancer therapy. ACS Appl Mater Interfaces, 12(27):30031-30043.

[38]LiY, GuoS, RenQJ, et al., 2018. Pharmacokinetic comparisons of multiple triterpenic acids from Jujubae fructus extract following oral delivery in normal and acute liver injury rats. Int J Mol Sci, 19(7):2047.

[39]LiYT, BaoT, ChenW, 2018. Comparison of the protective effect of black and white mulberry against ethyl carbamate-induced cytotoxicity and oxidative damage. Food Chem, 243:65-73.

[40]LiZY, BuQT, WangJ, et al., 2019. Activation of anthrachamycin biosynthesis in Streptomyces chattanoogensis L10 by site-directed mutagenesis of rpoB. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(12):983-994.http://doi.org/10.1631/jzus.B1900344

[41]LinDR, XiaoMS, ZhaoJJ, et al., 2016. An overview of plant phenolic compounds and their importance in human nutrition and management of type 2 diabetes. Molecules, 21(10):1374.

[42]LucaSV, MacoveiI, BujorA, et al., 2020. Bioactivity of dietary polyphenols: the role of metabolites. Crit Rev Food Sci Nutr, 60(4):626-659.

[43]LuoJ, MillsK, le CessieS, et al., 2020. Ageing, age-related diseases and oxidative stress: what to do next? Ageing Res Rev, 57:100982.

[44]LvHH, ZhenCX, LiuJY, et al., 2019. Unraveling the potential role of glutathione in multiple forms of cell death in cancer therapy. Oxid Med Cell Longev, 2019:3150145.

[45]MillerGL, 1959. Use of dinitrosalicylic acid reagent for determination of reducing sugar. Anal Chem, 31(3):426-428.

[46]MojzerEB, HrnčičMK, ŠkergetM, et al., 2016. Polyphenols: extraction methods, antioxidative action, bioavailability and anticarcinogenic effects. Molecules, 21(7):901.

[47]MozaffarianD, WuJHY, 2018. Flavonoids, dairy foods, and cardiovascular and metabolic health: a review of emerging biologic pathways. Circ Res, 122(2):369-384.

[48]MurphyMP, 2016. Understanding and preventing mitochondrial oxidative damage. Biochem Soc Trans, 44(5):1219-1226.

[49]NiedzwieckiA, RoomiMW, KalinovskyT, et al., 2016. Anticancer efficacy of polyphenols and their combinations. Nutrients, 8(9):552.

[50]PahujaM, MehlaJ, ReetaKH, et al., 2011. Hydroalcoholic extract of Zizyphus jujuba ameliorates seizures, oxidative stress, and cognitive impairment in experimental models of epilepsy in rats. Epilepsy Behav, 21(4):356-363.

[51]PeriasamyS, WuWH, ChienSP, et al., 2020. Dietary Ziziphus jujuba fruit attenuates colitis-associated tumorigenesis: a pivotal role of the NF-κB/IL-6/JAK1/STAT3 pathway. Nutr Cancer, 72(1):120-132.

[52]PlastinaP, BonofiglioD, VizzaD, et al., 2012. Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells. J Ethnopharmacol, 140(2):325-332.

[53]PodszunMC, AlawadAS, LingalaS, et al., 2020. Vitamin E treatment in NAFLD patients demonstrates that oxidative stress drives steatosis through upregulation of de-novo lipogenesis. Redox Biol, 37:101710.

[54]RavisankarS, AgahS, KimH, et al., 2019. Combined cereal and pulse flavonoids show enhanced bioavailability by downregulating phase II metabolism and ABC membrane transporter function in Caco-2 model. Food Chem, 279:88-97.

[55]ReddyPH, 2006. Amyloid precursor protein-mediated free radicals and oxidative damage: implications for the development and progression of Alzheimer’s disease. J Neurochem, 96(1):1-13.

[56]RochaM, ApostolovaN, Diaz-RuaR, et al., 2020. Mitochondria and T2D: role of autophagy, ER stress, and inflammasome. Trends Endocrinol Metab, 31(10):725-741.

[57]RowlandI, GibsonG, HeinkenA, et al., 2018. Gut microbiota functions: metabolism of nutrients and other food components. Eur J Nutr, 57(1):1-24.

[58]SinghRK, ChangHW, YanD, et al., 2017. Influence of diet on the gut microbiome and implications for human health. J Transl Med, 15(1):73.

[59]SingletonVL, RossiJA, 1965. Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am J Enol Vitic, 16(3):144-158.

[60]SiracusaL, Kulisic-BilusicT, PoliteoO, et al., 2011. Phenolic composition and antioxidant activity of aqueous infusions from Capparis spinosa L. and Crithmum maritimum L. before and after submission to a two-step in vitro digestion model. J Agric Food Chem, 59(23):12453-12459.

[61]SpagnuoloC, NapolitanoM, TedescoI, et al., 2016. Neuroprotective role of natural polyphenols. Curr Top Med Chem, 16(17):1943-1950.

[62]SuHM, XieLH, XuY, et al., 2020. Pelargonidin-3-O-glucoside derived from wild raspberry exerts antihyperglycemic effect by inducing autophagy and modulating gut microbiota. J Agric Food Chem, 68(46):13025-13037.

[63]TsengCY, WangJS, ChaoMW, 2017. Causation by diesel exhaust particles of endothelial dysfunctions in cytotoxicity, pro-inflammation, permeability, and apoptosis induced by ROS generation. Cardiovasc Toxicol, 17(4):384-392.

[64]WangB, 2011. Chemical characterization and ameliorating effect of polysaccharide from Chinese jujube on intestine oxidative injury by ischemia and reperfusion. Int J Biol Macromol, 48(3):386-391.

[65]WangSM, HuangYW, XuHH, et al., 2017. Oxidized tea polyphenols prevent lipid accumulation in liver and visceral white adipose tissue in rats. Eur J Nutr, 56(6):2037-2048.

[66]YahfoufiN, AlsadiN, JambiM, et al., 2018. The immunomodulatory and anti-inflammatory role of polyphenols. Nutrients, 10(11):1618.

[67]ZhangL, LiuPZ, LiLL, et al., 2018. Identification and antioxidant activity of flavonoids extracted from Xinjiang jujube (Ziziphus jujube Mill.) leaves with ultra-high pressure extraction technology. Molecules, 24(1):122.

[68]ZhangWJ, LiuC, YangRJ, et al., 2019. Comparison of volatile profiles and bioactive components of sun-dried Pu-erh tea leaves from ancient tea plants on Bulang Mountain measured by GC-MS and HPLC. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(7):563-575.http://doi.org/10.1631/jzus.B1800183

[69]ZhaoHX, ZhangHS, YangSF, 2014. Phenolic compounds and its antioxidant activities in ethanolic extracts from seven cultivars of Chinese jujube. Food Sci Hum Well, 3(3-4):183-190.

[70]ZhaoXR, DuGC, ZouHJ, et al., 2013. Progress in preventing the accumulation of ethyl carbamate in alcoholic beverages. Trends Food Sci Technol, 32(2):97-107.

[71]ZhuXR, WangH, SunJ, et al., 2019. Pericarp and seed of litchi and longan fruits: constituent, extraction, bioactive activity, and potential utilization. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(6):503-512.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - Journal of Zhejiang University-SCIENCE