Sources and biological functions of citrus polymethoxy flavones

Authors

ZHANG Mengling, Longping Branch Graduate School of Hunan University, Changsha, Hunan 410125, China; Hunan Agriculture Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha, Hunan 410125 China; School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China; Hunan Key Lab of Fruits & Vegetables Storage, Processing, Quality and Safety, Changsha, Hunan 410125, China
LI Qili, Longping Branch Graduate School of Hunan University, Changsha, Hunan 410125, China; Hunan Agriculture Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha, Hunan 410125 China; Hunan Key Lab of Fruits & Vegetables Storage, Processing, Quality and Safety, Changsha, Hunan 410125, China
LI Gaoyang, Longping Branch Graduate School of Hunan University, Changsha, Hunan 410125, China; Hunan Agriculture Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha, Hunan 410125 China; Hunan Key Lab of Fruits & Vegetables Storage, Processing, Quality and Safety, Changsha, Hunan 410125, China
FU Fuhua, Longping Branch Graduate School of Hunan University, Changsha, Hunan 410125, China; Hunan Agriculture Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha, Hunan 410125 China; Hunan Key Lab of Fruits & Vegetables Storage, Processing, Quality and Safety, Changsha, Hunan 410125, China
XIAO Yecheng, Lianyuan Kang Biotechnology Co., Ltd., Loudi, Hunan 417000, China
SHAN Yang, Longping Branch Graduate School of Hunan University, Changsha, Hunan 410125, China; Hunan Agriculture Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha, Hunan 410125 China; Hunan Key Lab of Fruits & Vegetables Storage, Processing, Quality and Safety, Changsha, Hunan 410125, China
YU Huanling, School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China

Abstract

This study reviewed the sources and biological functions of polymethoxy flavones, and discussed the existing problems in the current research.

Publication Date

1-28-2019

First Page

213

Last Page

220,236

DOI

10.13652/j.issn.1003-5788.2019.01.038

Recommended Citation

Mengling, ZHANG; Qili, LI; Gaoyang, LI; Fuhua, FU; Yecheng, XIAO; Yang, SHAN; and Huanling, YU (2019) "Sources and biological functions of citrus polymethoxy flavones," Food and Machinery: Vol. 35: Iss. 1, Article 38.
DOI: 10.13652/j.issn.1003-5788.2019.01.038
Available at: https://www.ifoodmm.cn/journal/vol35/iss1/38

References

[1] Food and Agriculture Organization. Citrus fruit fresh and processed, statistical bulletin 2016[R]. [S.l.]: FAO, 2017.
[2] 单杨. 现代柑橘工业[M]. 北京: 化学工业出版社, 2013: 334-378.
[3] LI Pei-jun, XIA Jin-lan, NIE Zhen-yuan, et al. Pectic oligosaccharides hydrolyzed from orange peel by fungal multi-enzyme complexes and their prebiotic and antibacterial potentials[J]. LWT-Food Science and Technology, 2016, 69: 203-210.
[4] ZHANG Ning, ZHENG Yang, XIANG Shi-zhao, et al. Nobiletin attenuates cardiac dysfunction, oxidative stress, and inflammatory in streptozotocin: induced diabetic cardiomyopathy[J]. Molecular and Cellular Biochemistry, 2016, 417(1/2): 87-96.
[5] WANG Yue, QIAN Jing, CAO Jin-ping, et al. Antioxidant capacity, anticancer ability and flavonoids composition of 35 citrus (citrus reticulata blanco) varieties[J]. Molecules, 2017, 22(7): 1 114-1 133.
[6] HAMADA Y, NAKAJIMA M, TSUZUKI K, et al. Heptamethoxyflavone reduces phosphodiesterase activity and T-cell growth in vitro[J]. International Archives of Allergy and Immunology, 2017, 174(3/4): 113-120.
[7] PARKAR N A, BHATT L K, ADDEPALLI V. Efficacy of nobiletin, a citrus flavonoid, in the treatment of the cardiovascular dysfunction of diabetes in rats[J]. Food and Function, 2016, 7(7): 3 121-3 129.
[8] LI Wei-feng, ZHAO Ruo-qi, WANG Xiu-mei, et al. Nobiletin-ameliorated lipopolysaccharide-induced inflammation in acute lung injury by suppression of NF-κB pathway in vivo, and vitro[J]. Inflammation, 2018, 41(3): 996-1 007.
[9] NAKAJIMA A, OHIZUMI Y, YAMADA K. Anti-dementia activity of nobiletin, a citrus flavonoid a review of animal studies[J]. Clinical Psychopharmacology and Neuroscience the Official Scientific Journal of the Korean College of Neuropsychopharmacology, 2014, 12(2): 75-82.
[10] YABUKI Y, OHIZUMI Y, YOKOSUKA A, et al. Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced parkinson model mice[J]. Neuroscience, 2014, 259(4): 126-141.
[11] OKUYAMA S, MORITA M, MIYOSHI K, et al. 3,5,6,7,8,3′,4′-Heptamethoxyflavone, a citrus flavonoid, on protection against memory impairment and neuronal cell death in a global cerebral ischemia mouse model[J]. Neurochemistry International, 2014, 70: 30-38.
[12] MATSUMOTO C, INOUE H, TOMINARI T, et al. Heptamethoxyflavone, a citrus flavonoid, suppresses inflammatory osteoclastogenesis and alveolar bone resorption[J]. Bioscience Biotechnology and Biochemistry, 2015, 79(1): 155-158.
[13] KUROWSKA E M, MANTHEY J A. Hypolipidemic effects and absorption of citrus polymethoxylated flavones in hamsters with diet-induced hypercholesterolemia[J]. Journal of Agricultural and Food Chemistry, 2004, 52(10): 2 879-2 886.
[14] WHITMAN S C, KUROWSKA E M, MANTHEY J A, et al. Nobiletin, a citrus flavonoid isolated from tangerines, selectively inhibits class a scavenger receptor-mediated metabolism of acetylated LDL by mouse macrophages[J]. Atherosclerosis, 2005, 178(1): 25-32.
[15] AMAKURA Y, YOSHIMURA M, OUCHI K, et al. Characterization of constituents in the peel of citrus kawachiensis (kawachibankan)[J]. Bioscience Biotechnol-ogy and Biochemistry, 2013, 77(9): 1 977-1 980.
[16] HUNG Wei-lun, CHANG Wei-shan, LU Wen-chien, et al. Pharmacokinetics, bioavailability, tissue distribution and excretion of tangeretin in rat[J]. Journal of Food and Drug Analysis, 2018, 26: 849-857.
[17] CIRMI S, MAUGERI A, FERLAZZO N, et al. Anticancer potential of citrus juices and their extracts: a systematic review of both preclinical and clinical studies[J]. Front Pharmacol, 2017, 8: 420.
[18] SWIFT L J．Tetra-O-methylscutellarein in orange peel[J]. Journal of Organic Chemistry,1965, 30(6): 2 079-2 080.
[19] SWIFT L J. Thin-layer chromatographic-spectrophotome-tric analysis for neutral fraction flavones in orange peel juice[J]. Journal of Agricultural and Food Chemistry, 1967, 15(1): 99-101.
[20] OOGHE W C, OOGHE S J, DETAVERNIER C M, et a1. Characterization of orange juice (citrus sinensis) by polymethoxylated flavones[J]. Journal of Agricultural and Food Chemistry, 1994, 42(10): 2 191-2 195.
[21] LI Shi-ming, WANG Hong, GUO Li-min, et al. Chemistry and bioactivity of nobiletin and its metabolites[J]. Journal of Function Foods, 2014, 6: 2-10.
[22] LEWIN G, MACIUK A, THORET S, et al. Semisynthesis of natural flavones inhibiting tubulin polymerization, from hesperidin[J]. Journal of Natural Products, 2010, 73(4): 702-706.
[23] WESOOWSKA O, WISNIEWSKI J, SRODAPOMIAN-EK K, et al. Multidrug resistance reversal and apoptosis induction in human colon cancer cells by some flavonoids present in citrus plants[J]. Journal of Natural Products, 2012, 75(11): 1 896-1 902.
[24] IOANNOU I. Extraction methods of citrus peel phenolic compounds[J]. Food Reviews International, 2014, 30(4): 265-290.
[25] RAMAN G, JAYAPRAKASHA G K, CHO M, et al. Rapid adsorptive separation of citrus polymethoxylated flavones in non-aqueous conditions[J]. Separation and Purification Technology, 2005, 45(2): 147-152.
[26] ZHENG Jin-kai, BI Jin-feng, JOHNSON D, et al. Analysis of 10 metabolites of polymethoxyflavones with high sensitivity by electrochemical detection in high-performance liquid chromatography[J]. Journal of Agricultural and Food Chemistry, 2015, 63(2): 509-516.
[27] UCKOO R M, PATIL B S. Rapid separation method of polymethoxyflavones from citrus using flash chromatograp-hy[J]. Separation and Purification Technology, 2011, 81(2): 151-158.
[28] ITOH N, IWATA C, TODA H. Molecular cloning and characterization of a flavonoid-O-methyltransferase with broad substrate specificity and regioselectivity from Citrus depressa[J]. Bmc Plant Biology, 2016, 16(1): 180.
[29] HE Zhen-xing, LI Xuan-fei, CHEN Hao, et al. Nobiletin attenuates lipopolysaccharide/D-galactosamine-induced liver injury in mice by activating the Nrf2 antioxidant pathway and subsequently inhibiting NF-κB-mediated cytokine production[J]. Molecular Medicine Reports, 2016, 14(6): 5 595-5 600.
[30] ZHANG Ning, WEI Wen-yin, YANG Zheng, et al. Nobiletin, a polymethoxy flavonoid, protects against cardiac hypertrophy induced by pressure-overload via inhibition of NAPDH oxidases and endoplasmic reticulum stress[J]. Cellular Physiology and Biochemistry, 2017, 42(4): 1 313-1 325.
[31] LIANG Fu-qiang, FANG Ya-jing, CAO Wei-wei, et al. Attenuation of tert-butyl hydroperoxide (τ-BHP)-induced oxidative damage in HepG2 cells by tangeretin: relevance of the Nrf2-ARE and MAPK Signaling Pathways[J]. Journal of Agricultural and Food Chemistry, 2018, 66(25): 6 317-6 325.
[32] MURAKAMI A, KUWAHARA S, TAKAHASHI Y, et al. In vitro absorption and metabolism of Nobiletid: n, a chemopreventive polymethoxyflavonoid in citrus fruits[J]. Bioscience Biotechnology and Biochemistry, 2001, 65(1): 194-197.
[33] CHOI S Y, KO H C, KO S Y, et al. Correlation between flavonoid content and the NO production inhibitory activity of peel extracts from various citrus fruits[J]. Biological and Pharmaceutical Bulletin, 2007, 30(4): 772-778.
[34] LIM S W, LEE D R, CHOI B K, et al. Protective effects of a polymethoxy flavonoids-rich Citrus aurantium peel extract on liver fibrosis induced by bile duct ligation in mice[J]. Asian Pacific Journal of Tropical Medicine, 2016, 9(12): 1 158-1 164.
[35] MORWOOD C J, LAPPAS M. The citrus flavone nobiletin reduces pro-inflammatory and pro-labour mediators in fetal membranes and myometrium: implications for preterm birth [J]. Plos One, 2014, 9(9): e108 390.
[36] HO S C, KUO C T. Hesperidin, nobiletin, and tangeretin are collectively responsible for the anti-neuroinflammatory capacity of tangerine peel (citri reticulatae pericarpium)[J]. Food and Chemical Toxicology, 2014, 71(71): 176-182.
[37] GUO Shan-shan, QIU Pei-ju, XU Guang, et al. Synergistic anti-inflammatory effects of nobiletin and sulforaphane in lipopolysaccharide-stimulated RAW 264.7 cells[J]. Journal of Agricultural and Food Chemistry, 2012, 60(9): 2 157.
[38] LIN N, SATO T, TAKAYAMA Y, et al. Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages[J]. Biochemical Pharmacology, 2003, 65(12): 2 065-2 071.
[39] YOSHIGAI E, MACHIDA T, OKUYAMA T, et al. Citrus nobiletin suppresses inducible nitric oxide synthase gene expression in interleukin-1β-treated hepatocytes[J]. Biochemical and Biophysical Research Communications, 2013, 439(1): 54-59.
[40] TANAKA S, SATO T, AKIMOTO N, et al. Prevention of UVB-induced photoinflammation and photoaging by a polymethoxy flavonoid, nobiletin, in human keratinocytes in vivo and in vitro[J]. Biochemical Pharmacology, 2004, 68(3): 433-439.
[41] ONISHI S, NISHI K, YASUNAGA S, et al. Nobiletin, a polymethoxy flavonoid, exerts anti-allergic effect by suppressing activation of phosphoinositide 3-kinase[J]. Journal of Functional Foods, 2014, 6(1): 606-614.
[42] JANG S E, RYU K R, PARK S H, et al. Nobiletin and tangeretin ameliorate scratching behavior in mice by inhibiting the action of histamine and the activation of NF-κB, AP-1 and p38 [J]. International Immunopharmacology, 2013, 17(3): 502-507.
[43] BENAVENTEGARCA O, CASTILLO J. Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity[J]. Journal of Agricultural and Food Chemistry, 2008, 56(15): 6 185-6 205.
[44] HOOPER L, KAY C, ABDELHAMID A, et al. Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials[J]. American Journal of Clinical Nutrition, 2012, 95(3): 740-751.
[45] VAIYAPURI S, ROWETH H, ALI M S, et al. Pharmacological actions of nobiletin in the modulation of platelet function[J]. British Journal of Pharmacology, 2015, 172(16): 4 133-4 145.
[46] MULVIHILL E E, HUFF M W. Protection from metabolic dysregulation, obesity, and atherosclerosis by citrus flavonoids: activation of hepatic PGC1α-mediated fatty acid oxidation[J]. Ppar Research, 2012, 274(3): 857 142.
[47] LI R W, THERIAULT A G, AU K, et al. Citrus polymethoxylated flavones improve lipid and glucose homeostasis and modulate adipocytokines in fructose-induced insulin resistant hamsters[J]. Life Sciences, 2006, 79(4): 365-373.
[48] EGUCHI A, MURAKAMI A, OHIGASHI H. Nobiletin, a citrus flavonoid, suppresses phorbol ester-induced expression of multiple scavenger receptor genes in THP[J]. FEBS Letters, 2006, 580: 3 321-3 328.
[49] LIN Y, VERMEER M A, BOS W. Molecular structures of citrus flavonoids determine their effects on lipid metabolism in HepG2 cells by primarily suppressing ApoB secretion[J]. Journal of Agricultural and Food Chemistry, 2011, 59(9): 4 496-4 503.
[50] YEN Jui-hung, WENG Ching-yi, LI Shi-ming, et al. Citrus flavonoid 5-demethylnobiletin suppresses scavenger receptor expression in THP-1 cells and alters lipid homeostasis in HepG2 liver cells[J]. Molecular Nutrition and Food Research, 2011, 55(5): 733-748.
[51] HE B, NOHARA K, PARK N, et al. The small molecule nobiletin targets the molecular oscillator to enhance circadian rhythms and protect against metabolic syndrome[J]. Cell Metabolism, 2016, 23(4): 610-621.
[52] SHINOZAKI A, MISAWA K, IKEDA Y, et al. Potent effects of flavonoid nobiletin on amplitude, period, and phase of the circadian clock rhythm in PER2::LUCIFERASE mouse embryonic fibroblasts[J]. Plos One, 2017, 12(2): e0 170 904.
[53] MIYATA Y, TANAKA H, SHIMADA A, et al. Regulation of adipocytokine secretion and adipocyte hypertrophy by polymethoxyflavonoids, nobiletin and tangeretin[J]. Life Sciences, 2011, 88(13/14): 613-618.
[54] SAITO T, ABE D, SEKIYA K. Nobiletin enhances differentiation and lipolysis of 3T3-L1 adipocytes[J]. Biochemical and Biophysical Research Communications, 2007, 357(2): 371-376.
[55] KUNIMASA K, KURANUKI S, MATSUURA N, et al. Identification of nobiletin, a polymethoxyflavonoid, as an enhancer of adiponectin secretion[J]. Bioorganic and Medicinal Chemistry Letters, 2009, 19(7): 2 062-2 064.
[56] YASUDA N, ISHII T, DAI O, et al. Neuroprotective effect of nobiletin on cerebral ischemia-reperfusion injury in transient middle cerebral artery-occluded rats[J]. Brain Research, 2014, 1 559(17): 46-54.
[57] ZHOU Cheng-hua, WU Xiao-hong, WU Yu-qing. Nobile-tin, a dietary phytochemical, inhibits vascular smooth muscle cells proliferation via calcium-mediated c-Jun N-terminal kinases pathway[J]. European Journal of Pharmacology, 2009, 615(1): 55-60.
[58] KOHNO H, YOSHITANI S, TSUKIO Y, et al. Dietary administration of citrus nobiletin inhibits azoxymethane-induced colonic aberrant crypt foci in rats[J]. Life Sciences, 2001, 69(8): 901-913.
[59] SUZUKI R, KOHNO H, MURAKAMI A, et al. Citrus Nobiletin inhibits azoxymethane-induced large bowel carcinogenesis in rats[J]. Biofactors, 2004, 21(1/2/3/4): 111-114.
[60] KUNIMASA K, IKEKITA M, SATO M, et al. Nobiletin, a citrus polymethoxy flavonoid, suppresses multiple angiogenesis-related endothelial cell functions and angiogenesis in vivo[J]. Cancer Science, 2010, 101: 2 462-2 469.
[61] CHEN Jian-chu, CHEN A Y, HUANG Hai-zhi, et al. The flavonoid nobiletin inhibits tumor growth and angiogenesis of ovarian cancers via the Akt pathway [J]. International Journal of Oncology, 2015, 46(6): 2 629-2 638.
[62] QIU Pei-ju, DONG Ping, GUAN Hua-shi, et al. Inhibitory eects of 5-hydroxy polymethoxyavones on colon cancer cells[J]. Molecular Nutrition and Food Research, 2010, 54: S244-S252.
[63] AKAO Y, ITOH T, OHGUCHI K, et al. Interactive effects of polymethoxy flavones from citrus on cell growth inhibition in human neuroblastoma SH-SY5Y cells[J]. Bioorganic and Medicinal Chemistry, 2008, 16(6): 2 803-2 810.
[64] CHIEN S Y, HSIEH M J, CHEN C J, et al. Nobiletin inhibits invasion and migration of human nasopharyngeal carcinoma cell lines by involving ERK1/2 and transcriptional inhibition of MMP-2[J]. Expert Opinion on Therapeutic Targets, 2015, 19(3): 307-320.
[65] LEE Y C, CHENG T H, LEE J S, et al. Nobiletin, a citrus flavonoid, suppresses invasion and migration involving FAK/PI3K/Akt and small GTPase signals in human gastric adenocarcinoma AGS cells[J]. Molecular and Cellular Biochemistry, 2011, 347(1/2): 103-115.
[66] BAEK S H, KIM S M, NAM D, et al. Antimetastatic effect of nobiletin through the down-regulation of CXC chemokine receptor type 4 and matrix metallopeptidase-9[J]. Pharmaceutical Biology, 2012, 50(10): 1 210-1 218.
[67] NIETO M A. Epithelial-Mesenchymal Transitions in development and disease: old views and new perspectives [J]. International Journal of Developmental Biology, 2009, 53(8/9/10): 1 541-1547.
[68] HOU Min-zhi, CHENG Zhi-qiang, SHEN Hong-wei, et al. High expression of CTHRC1 promotes EMT of epithelial ovarian cancer (EOC) and is associated with poor prognosis[J]. Oncotarget, 2015, 6(34): 35 813-35 829.
[69] DA Chun-li, LIU Yu-ting, ZHAN Yi-yi, et al. Nobiletin inhi-bits epithelial-mesenchymal transition of human non-small cell lung cancer cells by antagonizing the TGF-β1/Smad3 signaling pathway[J]. Oncology Reports, 2016, 35(5): 2 767-2 774.
[70] FENG Sen-ling, YUAN Zhong-wen, YAO Xiao-jun, et al. Tangeretin, a citrus pentamethoxyflavone, antagonizes ABCB1-mediated multidrug resistance by inhibiting its transport function[J]. Pharmacological Research, 2016, 110: 193-204.
[71] LAI C S, HO M H, TSAI M L, et al. Suppression of adipogenesis and obesity in high-fat induced mouse model by hydroxylated polymethoxyflavones[J]. Journal of Agricultural and Food Chemistry, 2013, 61(43): 10 320-10 328.
[72] CHAROENSINPHON N, QIU P, PING D, et al. 5-Demethyltangeretin inhibits human nonsmall cell lung cancer cell growth by inducing G₂/M cell cycle arrest and apoptosis[J]. Molecular Nutrition and Food Research, 2013, 57(12): 2 103-2 111.
[73] ZHENG Jin-kai, SONG Ming-yue, DONG Ping, et al. Identification of novel bioactive metabolites of 5-demethylNobiletin in mice[J]. Molecular Nutrition and Food Research, 2013, 57(11): 1 999-2 007.
[74] HEIM K E, TAGLIAFERRO A R, BOBILYA D J. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships[J]. The Journal of Nutritional Biochemistry, 2002, 13(10): 572-584.
