Abstract
Oxidative stress has very close relationship with human health, and human organsviolated by oxidative stress is likely to cause a series of physical diseases，such as headache, muscle aches, arthritis, atherosclerosis, diabetes, heart disease, cancer and neurodegenerative problem. However the flavonoids which widely exist in fruits, vegetables and other plant foods have a very significant role in the fight against oxidative stress, this is largely because it can activate the Nrf2-ARE which is the critical defense signaling pathway and regulating many antioxidant gene expression. In this paper, introduced the activation of Nrf2-ARE signaling pathway, the related signaling pathways of regulating Nrf2-ARE activation, the downstream genes regulated by Nrf2-ARE, and the influence of the Nrf2-ARE applied to inflammatory and apoptosis reaction. Meanwhile reviewed the research progress of eight kinds of flavonoids on the Nrf2-ARE signaling pathway and put forward the main scientific problems and solution strategy of the present study to provide reference for study of flavonoids in the field of prevention and treatment of oxidative stress-related diseases.
Publication Date
6-28-2016
First Page
201
Last Page
207
DOI
10.13652/j.issn.1003-5788.2016.06.048
Recommended Citation
Tao, LI; Fangming, DENG; Si, QIN; Yanyang, WU; Yang, SHAN; and Qili, LI
(2016)
"Advances in Nrf2-ARE-mediated flavonoids against oxidative stress,"
Food and Machinery: Vol. 32:
Iss.
6, Article 48.
DOI: 10.13652/j.issn.1003-5788.2016.06.048
Available at:
https://www.ifoodmm.cn/journal/vol32/iss6/48
References
[1] MARCELLO Iriti, ELENA Maria Varoni. Chemopreventive Potential of Flavonoids in Oral Squamous Cell Carcinoma in Human Studies[J]. Nutrients, 2013, 5: 2 564-2 576.
[2] 戈孟雪, 屈强, 周宏灏. 调控Nrf2-Keap1-ARE 信号通路的中药有效成分研究进展[J]. 中国临床药理学与治疗学, 2015, 20(6): 707-712.
[3] NGUYEN T, SHERRATT P J, PIEKETT C B. Regulatory mechanisms controlling gene expression mediated by the antioxidant response element[J]. Annual Revi. Pharmacol Toxicol, 2003(43): 233-236.
[4] HU Yuan-yuan, HOU Zuo-xu, LIU Dong-yang, et al. Tartary buckwheat flavonoids protect hepatic cells against high glucose-induced oxidative stress and insulin resistance via MAPK signaling pathways[J]. Food & Function, 2016, 7: 1 523-1 536.
[5] YANG JH, SHIN BY, HAN JY, et al. Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes[J]. Toxicol Appl. Pharmacol, 2014, 274(2): 293-301.
[6] ZHAI Xiao-han, LIN Mu-sen, ZHANG Feng, et al. Dietary flavonoid genistein induces Nrf2 and phase II detoxification gene expression via ERKs and PKC pathways and protects against oxidative stress in Caco-2 cells[J]. Mol. Nutr. Food Res., 2013, 57(2): 249-259.
[7] LEE S E, JEONG SI, YANG H, et al. Fisetin induces Nrf2-mediated HO-1 expression through PKC-δ and p38 in human umbilical vein endothelial cells[J]. J. Cell Biochem., 2011, 112(9): 2 352-2 360.
[8] ESPINOSA C, PEREZ-LLAMAS F, GUARDIOLA FA, et al. Molecular mechanisms by which white tea prevents oxidative stress[J]. J. Physiol. Biochem., 2014, 70(4): 891-900.
[9] KRAJKA-KUZNIAK V, PALUSZCZAK J, OSZMIANSKI J, et al. Hawthorn (Crataegusoxyacantha L.) bark extract regulates antioxidant response element (ARE)-mediated enzyme expression via Nrf2 pathway activation in normal hepatocyte cell line[J]. Phytother Res., 2014, 28(4): 593-602.
[10] KIM J, CHA Y N, SURH Y J. A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders[J]. Mutat Res., 2010, 690: 12-23.
[11] 覃思, 蒋立文, 侯德兴. 膳食多酚生理功能的营养基因组学研究现状与展望[J]. 中国食品学报, 2011, 11(9): 155-169.
[12] SUN G Y, CHEN Zi-hong, JASMER K J, et al. Quercetin attenuates inflammatory responses in BV-2 microglial cells: role of mapks on the nrf2 pathway and induction of heme oxygenase-1[J]. PLoS One, 2015, doi: 10.1371/journal.pone.0141509.
[13] WANG Rui, ZHANG Cheng-yue, BAI Li-ping, et al. Flavonoids derived from liquorice suppress murine macrophage activation by up-regulating heme oxygenase-1 independent of Nrf2 activation[J]. International Immunopharmacology. 2015, 28(2): 917-924.
[14] NITURE S K, JAISWAL A K. Inhibitor of Nrf2 (INrf2 or Keap1) protein degrades Bcl-xL via phosphoglycerate mutase 5 and controls cellular apoptosis[J]. J. Biol. Chem., 2011, 286(52): 44 542-44 556.
[15] NITURE S K, JAISWAL A K. Nrf2 protein up-regulates antiapoptotic protein Bcl-2 and prevents cellular apoptosis[J]. J. Biol. Chem., 2012, 287(13): 9 873-9 886.
[16] NITURE S K, JAISWAL A K. Nrf2-induced antiapoptotic Bcl-xL protein enhances cell survival and drug resistance[J]. Free Radic. Biol. Med., 2013, 57: 119-131.
[17] STEPKOWSKI T M, KRUSZEWSKI M K. Molecular cross-talk between the NRF2/KEAP1 signaling pathway, autophagy, and apoptosis[J]. Free Radic. Biol. Med., 2011, 50(9): 1 186-1 195.
[18] HU Rong, CHEN Nan, YAO Jing, et al. The role of Nrf2 and apoptotic signaling pathways in oroxylin A-mediated responses in HCT-116 colorectal adenocarcinoma cells and xenograft tumors[J]. Anticancer Drugs, 2012, 23(6): 651-658.
[19] HSEU Y C, LEE M S, WU Chi-rei, et al. The chalconeflavokawain B induces G2/M cell-cycle arrest and apoptosis in human oral carcinoma HSC-3 cells through the intracellular ROS generation and downregulation of the Akt/p38 MAPK signaling pathway[J]. J. Agric. Food Chem., 2012, 60(9): 2 385-2 397.
[20] REIS L C, CARNEIRO L M, BRANCO C R, et al. Comparison of conventional microwave and focused microwave-assisted extraction to enhance the efficiency of the extraction of antioxidant flavonols from jocote pomace (Spondiaspurpurea L.)[J]. Plant Foods Hum. Nutr., 2015, 70: 160-169.
[21] PAI T V, SAWANT S Y, GHATAK A A, et al. Characterization of Indian beers: chemical composition and antioxidant potential[J]. J. Food Sci. Technol., 2015, 52(3): 1 414-1 423.
[22] ZENGIN G, UYSAL A, GUNES E, et al. Survey of phytochemical composition and biological effects of three extracts from a wild plant (Cotoneaster nummulariaFisch. et Mey.): a potential source for functional food ingredients and drug formulations[J]. PLoS One, 2014, 9(11): 1-13.
[23] ABBASI A M, SHAH M H, LI T, et al. Ethnomedicinal values, phenolic contents and antioxidant properties of wild culinary vegetables[J]. J. Ethnopharmacol, 2015, 162: 333-345.
[24] 代重山, 李道稳, 汤树生, 等. 槲皮素通过激活MAPK/Nrf2信号通路上调HO-1表达改善喹烯酮致LO2细胞的氧化应激及遗传毒性[C]//中国畜牧兽医学会兽医药理毒理学分会第十一届会员代表大会暨第十三次学术讨论会与中国毒理学会兽医毒理专业委员会第五次学术研讨会论文集. 长沙: 中国畜牧兽医学会兽医药理毒理学分会, 2015: 114-115.
[25] 邓玥, 揭琴丰, 郝丽萍, 等. 槲皮素通过促进Nrf2转位拮抗人肝细胞酒精性氧化损伤[J]. 营养学报, 2010, 32(6): 532-535.
[26] KIM J S, SONG H J, KO S K, et al. Quercetin-3-O-beta-d-glucurono pyranoside (QGC)-induced HO-1 expression through ERK and PI3K activation in cultured feline esophageal epithelial cells[J]. Fitoterapia, 2010, 81(2): 85-92.
[27] CARRASCO-POZO C, CASTILLO R L, BELTRAN C, et al. Molecular mechanisms of gastrointestinal protection by quercetin against indomethacin-induced damage: role of NF-κB and Nrf2[J]. J. Nutr. Biochem., 2016, 27: 289-298.
[28] LIANG Lu, GAO Chang, LUO Meng, et al. Dihydroquercetin (DHQ) induced HO-1 and NQO1 expression against oxidative stress through the Nrf2-dependent antioxidant pathway[J]. J. Agric. Food Chem., 2013, 61 (11): 2 755-2 761.
[29] MANIGANDAN K, MANIMARAN D, JAYARAJ R L, et al. Taxifolin curbs NF-κB-mediated Wnt/β-catenin signaling via up-regulating Nrf2 pathway in experimental colon carcinogenesis[J]. Biochimie, 2015, 119: 103-112.
[30] ILDEFONSO R R, SONIA R, LAURA B, et al. Procyanidin B2 induces Nrf2 translocation and glutathione S-transferase P1 expression via ERKs and p38-MAPK pathways and protect human colonic cells against oxidative stress[J]. European Journal of Nutrition, 2012, 51(7): 881-892.
[31] 江蓓, 李保应, 甄军晖, 等. 葡萄籽原花青素通过Nrf2调节糖尿病大鼠肾组织GSTM的表达[J]. 中国病理生理杂志, 2011, 27(8): 1 596-1 591.
[32] SAHIN K, TUZCU M, GENCOGLU H, et al. Epigallocatechin-3-gallate activates Nrf2/HO-1 signaling pathway in cisplatin-induced neph-rotoxicity in rats[J]. Life Science, 2010, 87(7/8): 240-245.
[33] NAIR S, BARVE A, KHOR T O, et al. Regulation of Nrf2-and AP-1-mediated gene expression by epigallocatechin-3-gallate and sulforaphanein prostate of Nrf2-knockout or C57BL/6J mice and PC-3 AP-1 human prostate cancer cells[J]. Acta. Pharmacologica Sinca, 2010, 31(9): 1 223-1 240.
[34] TSAI P Y, KA S M, CHANG Jia-ming, et al. Epigallocatechin -3- gallateprevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasomeaetivatk[J]. Free Radic. Biol. Med., 2011, 51(3): 744-754.
[35] 吴广, 符平, 周玉生, 等. 芹菜素抑制脂多糖诱导小鼠巨噬细胞分泌炎症介质的分子机制[J]. 中国免疫学杂志, 2015(6): 753-756.
[36] 陈洪忠, 李海珍, 任冬梅. 木犀草素对EA.hy926细胞Nrf2信号通路的激活作用及H2O2致氧化损伤的保护作用[J]. 山东大学学报: 医学版, 2014(11): 6-10.
[37] ZHANG Zai-jun, CUI Wei, LI Guo-hui, et al. Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving PKC and PI3K/AKT signaling pathways[J]. J. Agric. Food Chem., 2012, 60(33): 8 171-8 182.
[38] KANG C H, KIM M J, SEO M J, et al. 5-Hydroxy-3,6,7,8,3'4'-hexamethoxyflavone inhibits nitric oxide production inlipopolysaccharide-stimulated BV2 microglia via NF-κB suppression and Nrf-2-dependent heme oxygenase-1 induction[J]. Food Chem.Toxicol., 2013, 57: 119-125.
[39] LAKSHMI A, SUBRAMANIAN S P. Tangeretin ameliorates oxidative stress in the renal tissues of rats with experimental breast cancer induced by 7,12-dimethylbenz[a] anthracene[J]. Toxicol Lett., 2014, 229(2): 333-348.
[40] HSIAO P C, Lee W J, YANG S F, et al. Nobiletin suppresses the proliferation and nduces apoptosis involving MAPKs and caspase-8/-9/-3 signals in human acute myeloid leukemia cells[J]. Tumour Biol., 2014, 35(12): 11 903-11 911.
[41] WU Pei-shan, YEN Jui-hung, KOU Mei-chun, et al. Luteolin and apigenin attenuate 4-hydroxy-2-nonenal -mediated cell death through modulation of UPR, Nrf2-ARE and MAPK pathways in PC12 cells[J]. PLoS One. 2015, doi: 10.1371/journal.pone.0130599.
[42] HONG Yan, AN Zhong-ping. Hesperidin attenuates learning and memory deficits in APP/PS1 mice through activation of Akt/Nrf2 signaling and inhibition of RAGE/NF-κB signaling[J]. Arch. Pharm. Res., 2015, doi: 10.1007/s12272-015-0662-z.
[43] 黎荣, 徐灵源, 梁韬, 等. 葛根素对6-羟多巴胺所致帕金森病大鼠黑质组织Nrf2/ARE通路的影响[J]. 中国实验方剂学杂志, 2013, (19)6: 230-233.
[44] MA Jie-qiong, DING Jie, XIAO Zheng-hua, et al. Puerarin ameliorates carbon tetrachloride-induced oxidative DNA damage and inflammation in mouse kidney through ERK/Nrf2/ARE pathway[J]. Food Chem. Toxicol., 2014, 71: 264-271.
[45] ZHANG Jing, GUO Wen-shi, TIAN Bu-xian, et al. Puerarin attenuates cognitive dysfunction and oxidative stress in vascular dementia rats induced by chronic ischemia[J]. Int. J. ClinExpPathol, 2015, 8(5): 4 695-4 704.
[46] LI Cheng-chong, PAN Zhi, XU Tian-jiao, et al. Puerarin induces the upregulation of glutathione levels and nuclear translocation of Nrf2 through PI3K/Akt/GSK-3β signaling events in PC12 cells exposed to lead[J]. Neurotoxicol Teratol, 2014, 46: 1-9.
[47] SHIN P H, YEH C T, YEN G C. Anthocyanins induce the activation of phase II enzymes through the antioxidant response element pathway against oxidative stress-induced apoptosis[J]. Journal of Agricultural and Food Chemistry, 2007, 55(23): 9 427-9 435.
[48] JEONG J W, LEE W S, SHIN S C, et al. Anthocyanins downregulate lipopolysaccharide-induced inflammatory responses in BV2 microglial cells by suppressing the NF-κB and Akt/MAPKs signaling pathways[J]. International Journal of Molecular Sciences, 2013, 14(1): 1 502-1 515.
[49] YAN Xue-rui, WU Lin, LI Bin, et al. Cyanidin-3-o-glucoside induces apoptosis and inhibits migration of tumor necrosis factor-α-treated rat aortic smooth muscle cells[J]. Cardiovascular Toxicology, 2015, doi: 10.1007/s12012-015-9333-z.
[50] 崔俣, 马海英, 孔力. Nrf2/ARE通路与机体抗氧化机制的研究进展[J]. 吉林大学学报: 医学版, 2011, 37(1): 187-190.