Skip to content
2000
Volume 26, Issue 1
  • ISSN: 1389-2010
  • E-ISSN: 1873-4316

Abstract

Flavonoids are a class of polyphenolic compounds that can be classified into six distinct categories, namely isoflavonoids, flavanones, flavanols, flavonols, flavones, and anthocyanidins. These compounds are naturally occurring and can be found in a diverse range of plant species. Flavonoids, a class of bioactive compounds, are mostly obtained through the consumption of vegetables, fruits and plant-derived beverages such as wine, cocoa-based products and green tea. Flavonoids have been demonstrated to exhibit a diverse range of anticancer properties. These include the modulation of activities of enzymes involved in scavenging reactive oxygen species, involvement in cell cycle arrest, induction of apoptosis and autophagy, as well as suppression of cancer cell proliferation and invasiveness. Flavonoids exhibit a dual role in maintaining reactive oxygen species balance. They function as antioxidants in regular physiological conditions, while also demonstrating significant pro-oxidant properties in cancer cells. This pro-oxidant activity induces apoptotic pathways and downregulates pro-inflammatory signalling pathways. The paper explores the biochemical characteristics, bioavailability, anticancer efficacy, and modes of action of flavonoids.

Loading

Article metrics loading...

/content/journals/cpb/10.2174/0113892010297456240327062614
2024-04-08
2025-04-02
Loading full text...

Full text loading...

References

  1. NabaviS.M. ŠamecD. TomczykM. MilellaL. RussoD. HabtemariamS. SuntarI. RastrelliL. DagliaM. XiaoJ. GiampieriF. BattinoM. Sobarzo-SanchezE. NabaviS.F. YousefiB. JeandetP. XuS. ShirooieS. Flavonoid biosynthetic pathways in plants: Versatile targets for metabolic engineering.Biotechnol. Adv.20203810731610.1016/j.biotechadv.2018.11.005 30458225
    [Google Scholar]
  2. ScaranoA. ChieppaM. SantinoA. Looking at flavonoid biodiversity in horticultural crops: A colored mine with nutritional benefits.Plants2018749810.3390/plants7040098 30405037
    [Google Scholar]
  3. LiuJ. WangX. YongH. KanJ. JinC. Recent advances in flavonoid-grafted polysaccharides: Synthesis, structural characterization, bioactivities and potential applications.Int. J. Biol. Macromol.20181161011102510.1016/j.ijbiomac.2018.05.149 29800657
    [Google Scholar]
  4. KofinkM. PapagiannopoulosM. GalensaR. (-)-Catechin in cocoa and chocolate: Occurrence and analysis of an atypical flavan-3-ol enantiomer.Molecules20071271274128810.3390/12071274 17909484
    [Google Scholar]
  5. BraicuC. LadomeryM.R. ChedeaV.S. IrimieA. Berindan-NeagoeI. The relationship between the structure and biological actions of green tea catechins.Food Chem.201314133282328910.1016/j.foodchem.2013.05.122 23871088
    [Google Scholar]
  6. ArtsI.C.W. van de PutteB. HollmanP.C.H. Catechin contents of foods commonly consumed in The Netherlands. 2. Tea, wine, fruit juices, and chocolate milk.J. Agric. Food Chem.20004851752175710.1021/jf000026+ 10820090
    [Google Scholar]
  7. Määttä-RiihinenK.R. Kamal-EldinA. TörrönenA.R. Identification and quantification of phenolic compounds in berries of Fragaria and Rubus species (family Rosaceae).J. Agric. Food Chem.200452206178618710.1021/jf049450r 15453684
    [Google Scholar]
  8. WuX. GuL. PriorR.L. McKayS. Characterization of anthocyanins and proanthocyanidins in some cultivars of Ribes, Aronia, and Sambucus and their antioxidant capacity.J. Agric. Food Chem.200452267846785610.1021/jf0486850 15612766
    [Google Scholar]
  9. de Pascual-TeresaS. Santos-BuelgaC. Rivas-GonzaloJ.C. Quantitative analysis of flavan-3-ols in Spanish foodstuffs and beverages.J. Agric. Food Chem.200048115331533710.1021/jf000549h 11087482
    [Google Scholar]
  10. VrhovsekU. RigoA. TononD. MattiviF. Quantitation of polyphenols in different apple varieties.J. Agric. Food Chem.200452216532653810.1021/jf049317z 15479019
    [Google Scholar]
  11. LandbergR. NaidooN. van DamR.M. Diet and endothelial function.Curr. Opin. Lipidol.201223214715510.1097/MOL.0b013e328351123a 22327611
    [Google Scholar]
  12. MejriF. SelmiS. MartinsA. benkhoud, H.; Baati, T.; Chaabane, H.; Njim, L.; Serralheiro, M.L.M.; Rauter, A.P.; Hosni, K. Broad bean (Vicia faba L.) pods: a rich source of bioactive ingredients with antimicrobial, antioxidant, enzyme inhibitory, anti-diabetic and health-promoting properties.Food Funct.2018942051206910.1039/C8FO00055G 29589631
    [Google Scholar]
  13. RomaniA. MulinacciN. PinelliP. VincieriF.F. CimatoA. Polyphenolic content in five tuscany cultivars of Olea europaea L.J. Agric. Food Chem.199947396496710.1021/jf980264t 10552399
    [Google Scholar]
  14. SlimestadR. FossenT. VågenI.M. Onions: A source of unique dietary flavonoids.J. Agric. Food Chem.20075525100671008010.1021/jf0712503 17997520
    [Google Scholar]
  15. PandjaitanN. HowardL.R. MorelockT. GilM.I. Antioxidant capacity and phenolic content of spinach as affected by genetics and maturation.J. Agric. Food Chem.200553228618862310.1021/jf052077i 16248562
    [Google Scholar]
  16. FattorussoE. IorizziM. LanzottiV. Taglialatela-ScafatiO. Chemical composition of shallot (Allium ascalonicum Hort.).J. Agric. Food Chem.200250205686569010.1021/jf020396t 12236699
    [Google Scholar]
  17. Rodríguez-GarcíaC. Sánchez-QuesadaC. GaforioJ.J. Dietary flavonoids as cancer chemopreventive agents: An updated review of human studies.Antioxidants20198513710.3390/antiox8050137 31109072
    [Google Scholar]
  18. YahfoufiN. AlsadiN. JambiM. MatarC. The immunomodulatory and anti-inflammatory role of polyphenols.Nutrients20181011161810.3390/nu10111618 30400131
    [Google Scholar]
  19. AbotalebM. SamuelS. VargheseE. VargheseS. KubatkaP. LiskovaA. BüsselbergD. Flavonoids in cancer and apoptosis.Cancers20181112810.3390/cancers11010028 30597838
    [Google Scholar]
  20. ChirumboloS. BjørklundG. LysiukR. VellaA. LenchykL. UpyrT. Targeting cancer with phytochemicals via their fine tuning of the cell survival signaling pathways.Int. J. Mol. Sci.20181911356810.3390/ijms19113568 30424557
    [Google Scholar]
  21. ShenN. WangT. GanQ. LiuS. WangL. JinB. Plant flavonoids: Classification, distribution, biosynthesis, and antioxidant activity.Food Chem.202238313253110.1016/j.foodchem.2022.132531 35413752
    [Google Scholar]
  22. PancheA.N. DiwanA.D. ChandraS.R. Flavonoids: An overview.J. Nutr. Sci.20165e4710.1017/jns.2016.41 28620474
    [Google Scholar]
  23. ChenS. WangX. ChengY. GaoH. ChenX. A review of classification, biosynthesis, biological activities and potential applications of flavonoids.Molecules20232813498210.3390/molecules28134982 37446644
    [Google Scholar]
  24. IwashinaT. The structure and distribution of the flavonoids in plants.J. Plant Res.2000113328729910.1007/PL00013940
    [Google Scholar]
  25. KumarS. PandeyA.K. Chemistry and biological activities of flavonoids: An overview.ScientificWorldJournal2013201311610.1155/2013/162750 24470791
    [Google Scholar]
  26. AlamM.A. SubhanN. RahmanM.M. UddinS.J. RezaH.M. SarkerS.D. Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action.Adv. Nutr.20145440441710.3945/an.113.005603 25022990
    [Google Scholar]
  27. IzawaK. AminoY. KohmuraM. UedaY. KurodaM. Human–Environment interactions–taste.Comp. Nat. Prod.20104631671
    [Google Scholar]
  28. DimitriosT. VassilikiO. Polyphenols in Plants.2nd edAcademic Press2019263284
    [Google Scholar]
  29. MallaA. RamalingamS.K. Handbook of food bioengineering, role of materials science in food bioengineering.Academic Press2018353379
    [Google Scholar]
  30. MazurW. FotsisT. WähäläK. OjalaS. SalakkaA. AdlercreutzH. Isotope dilution gas chromatographic-mass spectrometric method for the determination of isoflavonoids, coumestrol, and lignans in food samples.Anal. Biochem.1996233216918010.1006/abio.1996.0025 8789715
    [Google Scholar]
  31. GarazdM.M. GarazdY.L. KhilyaV.P. Neoflavones. 1. Natural distribution and spectral and biological properties.Chem. Nat. Compd.20033915412110.1023/A:1024140915526
    [Google Scholar]
  32. LuqmanS. MeenaA. SinghP. KondratyukT.P. MarlerL.E. PezzutoJ.M. NegiA.S. Neoflavonoids and tetrahydroquinolones as possible cancer chemopreventive agents.Chem. Biol. Drug Des.201280461662410.1111/j.1747‑0285.2012.01439.x 22726671
    [Google Scholar]
  33. KumarP. AhamadT. MishraD.P. KhanM.F. Plant-derived Bioactives.SingaporeSpringer2020355710.1007/978‑981‑15‑2361‑8_3
    [Google Scholar]
  34. SalehiB. Sharifi-RadJ. CappelliniF. ReinerŽ. ZorzanD. ImranM. SenerB. KilicM. El-ShazlyM. FahmyN.M. Al-SayedE. MartorellM. TonelliC. PetroniK. DoceaA.O. CalinaD. MaroyiA. The therapeutic potential of anthocyanins: Current approaches based on their molecular mechanism of action.Front. Pharmacol.202011130010.3389/fphar.2020.01300 32982731
    [Google Scholar]
  35. GiustiM.M. WrolstadR.E. Acylated anthocyanins from edible sources and their applications in food systems.Biochem. Eng. J.200314321722510.1016/S1369‑703X(02)00221‑8
    [Google Scholar]
  36. HertogM.G.L. HollmanP.C.H. KatanM.B. Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in the Netherlands.J. Agric. Food Chem.199240122379238310.1021/jf00024a011
    [Google Scholar]
  37. JustesenU. KnuthsenP. Composition of flavonoids in fresh herbs and calculation of flavonoid intake by use of herbs in traditional Danish dishes.Food Chem.200173224525010.1016/S0308‑8146(01)00114‑5
    [Google Scholar]
  38. StewartA.J. BozonnetS. MullenW. JenkinsG.I. LeanM.E.J. CrozierA. Occurrence of flavonols in tomatoes and tomato-based products.J. Agric. Food Chem.20004872663266910.1021/jf000070p 10898604
    [Google Scholar]
  39. ZhengW. WangS.Y. Antioxidant activity and phenolic compounds in selected herbs.J. Agric. Food Chem.200149115165517010.1021/jf010697n 11714298
    [Google Scholar]
  40. ValavanidisA. VlachogianniT. Plant Polyphenols.Stud. Nat. Prod. Chem.20133926929510.1016/B978‑0‑444‑62615‑8.00008‑4
    [Google Scholar]
  41. KoesR. VerweijW. QuattrocchioF. Flavonoids: A colorful model for the regulation and evolution of biochemical pathways.Trends Plant Sci.200510523624210.1016/j.tplants.2005.03.002 15882656
    [Google Scholar]
  42. ArtsI.C.W. van de PutteB. HollmanP.C.H. Catechin contents of foods commonly consumed in The Netherlands. 1. Fruits, vegetables, staple foods, and processed foods.J. Agric. Food Chem.20004851746175110.1021/jf000025h 10820089
    [Google Scholar]
  43. Tomás‐BarberánF.A. CliffordM.N. Flavanones, chalcones and dihydrochalcones–nature, occurrence and dietary burden.J. Sci. Food Agric.20008071073108010.1002/(SICI)1097‑0010(20000515)80:7<1073:AID‑JSFA568>3.0.CO;2‑B
    [Google Scholar]
  44. HavsteenB.H. The biochemistry and medical significance of the flavonoids.Pharmacol. Ther.2002962-36720210.1016/S0163‑7258(02)00298‑X 12453566
    [Google Scholar]
  45. Gil-IzquierdoA. GilM.I. FerreresF. Tomás-BarberánF.A. In vitro availability of flavonoids and other phenolics in orange juice.J. Agric. Food Chem.20014921035104110.1021/jf0000528 11262068
    [Google Scholar]
  46. MiadokováE. Isoflavonoids: An overview of their biological activities and potential health benefits.Interdiscip. Toxicol.20092421121810.2478/v10102‑009‑0021‑3 21217857
    [Google Scholar]
  47. BravoL. Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance.Nutr. Rev.1998561131733310.1111/j.1753‑4887.1998.tb01670.x 9838798
    [Google Scholar]
  48. AherneS.A. O’BrienN.M. Dietary flavonols: Chemistry, food content, and metabolism.Nutrition2002181758110.1016/S0899‑9007(01)00695‑5 11827770
    [Google Scholar]
  49. TuanH.M. Food phytochemicals for cancer prevention II Fruits and vegetables. ACS Symposium series,USA 1994546
    [Google Scholar]
  50. HoC.T. Food phytochemicals for cancer prevention II.American Chemical Society199454710.1021/bk‑1994‑0547
    [Google Scholar]
  51. VoigtJ. Phenolic compounds in food and their effects on health. i. Analysis, occurrence, and chemistry.American Chemical Society. ChangY. Mou‐TuanH. Washington, DC Preis199274
    [Google Scholar]
  52. Benavente-GarcíaO. CastilloJ. MarinF.R. OrtuñoA. Del RíoJ.A. Uses and properties of citrus flavonoids.J. Agric. Food Chem.199745124505451510.1021/jf970373s 18593176
    [Google Scholar]
  53. SalehM.M. HashemF.A.E.M. GlombitzaK.W. Study of Citrus taitensis and radical scavenger activity of the flavonoids isolated.Food Chem.199863339740010.1016/S0308‑8146(97)00238‑0
    [Google Scholar]
  54. EtiévantP. SchlichP. BertrandA. SymondsP. BouvierJ.C. Varietal and geographic classification of French red wines in terms of pigments and flavonoid compounds.J. Sci. Food Agric.1988421395410.1002/jsfa.2740420106
    [Google Scholar]
  55. HostetlerG.L. RalstonR.A. SchwartzS.J. Flavones: Food sources, bioavailability, metabolism, and bioactivity.Adv. Nutr.20178342343510.3945/an.116.012948 28507008
    [Google Scholar]
  56. KozłowskaA. Szostak-WegierekD. Flavonoids--food sources and health benefits.Rocz. Panstw. Zakl. Hig.20146527985 25272572
    [Google Scholar]
  57. Flavonoids classification and natural sources. Available from: https://encyclopedia.pub/entry/2767
  58. CorcoranM.P. McKayD.L. BlumbergJ.B. Flavonoid basics: chemistry, sources, mechanisms of action, and safety.J. Nutr. Gerontol. Geriatr.201231317618910.1080/21551197.2012.698219 22888837
    [Google Scholar]
  59. RossJ.A. KasumC.M. Dietary flavonoids: Bioavailability, metabolic effects, and safety.Annu. Rev. Nutr.2002221193410.1146/annurev.nutr.22.111401.144957 12055336
    [Google Scholar]
  60. Waheed JanabiA.H. KambohA.A. SaeedM. XiaoyuL. BiBi, J.; Majeed, F.; Naveed, M.; Mughal, M.J.; Korejo, N.A.; Kamboh, R.; Alagawany, M.; Lv, H. Flavonoid-rich foods (FRF): A promising nutraceutical approach against lifespan-shortening diseases.Iran. J. Basic Med. Sci.2020232140153 32405356
    [Google Scholar]
  61. MurphyM.P. How mitochondria produce reactive oxygen species.Biochem. J.2009417111310.1042/BJ20081386 19061483
    [Google Scholar]
  62. HadiS.M. AsadS.F. SinghS. AhmadA. Putative mechanism for anticancer and apoptosis-inducing properties of plant-derived polyphenolic compounds.IUBMB Life200050316717110.1080/152165400300001471 11142343
    [Google Scholar]
  63. LinkA. BalaguerF. GoelA. Cancer chemoprevention by dietary polyphenols: Promising role for epigenetics.Biochem. Pharmacol.201080121771179210.1016/j.bcp.2010.06.036 20599773
    [Google Scholar]
  64. FragaC.G. GalleanoM. VerstraetenS.V. OteizaP.I. Basic biochemical mechanisms behind the health benefits of polyphenols.Mol. Aspects Med.201031643544510.1016/j.mam.2010.09.006 20854840
    [Google Scholar]
  65. KaushikS. ShyamH. AgarwalS. SharmaR. NagT.C. DwivediA.K. BalapureA.K. Genistein potentiates Centchroman induced antineoplasticity in breast cancer via PI3K/Akt deactivation and ROS dependent induction of apoptosis.Life Sci.201923911707310.1016/j.lfs.2019.117073 31751581
    [Google Scholar]
  66. JinS. ZhangQ.Y. KangX.M. WangJ.X. ZhaoW.H. Daidzein induces MCF-7 breast cancer cell apoptosis via the mitochondrial pathway.Ann. Oncol.201021226326810.1093/annonc/mdp499 19889614
    [Google Scholar]
  67. ChanK.K.L. SiuM.K.Y. JiangY. WangJ. LeungT.H.Y. NganH.Y.S. Estrogen receptor modulators genistein, daidzein and ERB-041 inhibit cell migration, invasion, proliferation and sphere formation via modulation of FAK and PI3K/AKT signaling in ovarian cancer.Cancer Cell Int.20181816510.1186/s12935‑018‑0559‑2 29743815
    [Google Scholar]
  68. TavsanZ. KayaliH.A. Flavonoids showed anticancer effects on the ovarian cancer cells: Involvement of reactive oxygen species, apoptosis, cell cycle and invasion.Biomed. Pharmacother.201911610900410.1016/j.biopha.2019.109004 31128404
    [Google Scholar]
  69. SalmaniJ.M.M. ZhangX.P. JacobJ.A. ChenB.A. Apigenin’s anticancer properties and molecular mechanisms of action: Recent advances and future prospectives.Chin. J. Nat. Med.201715532132910.1016/S1875‑5364(17)30052‑3 28558867
    [Google Scholar]
  70. SouzaR.P. Bonfim-MendonçaP.S. GimenesF. RattiB.A. KaplumV. BruschiM.L. NakamuraC.V. SilvaS.O. Maria-EnglerS.S. ConsolaroM.E.L. Oxidative stress triggered by apigenin induces apoptosis in a comprehensive panel of human cervical cancer-derived cell lines.Oxid. Med. Cell. Longev.2017201711810.1155/2017/1512745 28191273
    [Google Scholar]
  71. ChoiE.J. JungJ.Y. KimG.H. Genistein inhibits the proliferation and differentiation of MCF-7 and 3T3-L1 cells via the regulation of ERα expression and induction of apoptosis.Exp. Ther. Med.20148245445810.3892/etm.2014.1771 25009600
    [Google Scholar]
  72. SolomonL.A. AliS. BanerjeeS. MunkarahA.R. MorrisR.T. SarkarF.H. Sensitization of ovarian cancer cells to cisplatin by genistein: The role of NF-kappaB.J. Ovarian Res.200811910.1186/1757‑2215‑1‑9 19025644
    [Google Scholar]
  73. ShafieeG. SaidijamM. TavilaniH. GhasemkhaniN. KhodadadiI. Genistein induces apoptosis and inhibits proliferation of HT29 colon cancer cells.Int. J. Mol. Cell. Med.201653178191 27942504
    [Google Scholar]
  74. QinJ. TengJ. ZhuZ. ChenJ. HuangW.J. Genistein induces activation of the mitochondrial apoptosis pathway by inhibiting phosphorylation of Akt in colorectal cancer cells.Pharm. Biol.2016541747910.3109/13880209.2015.1014921 25880142
    [Google Scholar]
  75. DanciuC. AvramS. PavelI.Z. GhiulaiR. DeheleanC.A. ErsiliaA. MindaD. PetrescuC. MoacaE.A. SoicaC. Main isoflavones found in dietary sources as natural anti-inflammatory agents.Curr. Drug Targets201819784185310.2174/1389450118666171109150731 29141545
    [Google Scholar]
  76. LiuX. SuzukiN. LaxmiY.R.S. OkamotoY. ShibutaniS. Anti-breast cancer potential of daidzein in rodents.Life Sci.20129111-1241541910.1016/j.lfs.2012.08.022 23227466
    [Google Scholar]
  77. ParkH.J. JeonY.K. YouD.H. NamM.J. Daidzein causes cytochrome c-mediated apoptosis via the Bcl-2 family in human hepatic cancer cells.Food Chem. Toxicol.20136054254910.1016/j.fct.2013.08.022 23959101
    [Google Scholar]
  78. ZhangJ. WuD. Vikash; Song, J.; Wang, J.; Yi, J.; Dong, W. Hesperetin induces the apoptosis of gastric cancer cells via activating mitochondrial pathway by increasing reactive oxygen species.Dig. Dis. Sci.201560102985299510.1007/s10620‑015‑3696‑7 25972151
    [Google Scholar]
  79. SivagamiG. VinothkumarR. PreethyC.P. RiyasdeenA. AkbarshaM.A. MenonV.P. NaliniN. NaliniN. Role of hesperetin (a natural flavonoid) and its analogue on apoptosis in HT-29 human colon adenocarcinoma cell line: A comparative study.Food Chem. Toxicol.2012503-466067110.1016/j.fct.2011.11.038 22142698
    [Google Scholar]
  80. ElangoR. AthinarayananJ. SubbarayanV.P. LeiD.K.Y. AlshatwiA.A. Hesperetin induces an apoptosis-triggered extrinsic pathway and a p53- independent pathway in human lung cancer H522 cells.J. Asian Nat. Prod. Res.201820655956910.1080/10286020.2017.1327949 28537448
    [Google Scholar]
  81. SambanthamS. RadhaM. ParamasivamA. AnandanB. MalathiR. ChandraS.R. JayaramanG. Molecular mechanism underlying hesperetin-induced apoptosis by in silico analysis and in prostate cancer PC-3 cells.Asian Pac. J. Cancer Prev.20131474347435210.7314/APJCP.2013.14.7.4347 23992001
    [Google Scholar]
  82. BaoL. LiuF. GuoH. LiY. TanB. ZhangW. PengY. Naringenin inhibits proliferation, migration, and invasion as well as induces apoptosis of gastric cancer SGC7901 cell line by downregulation of AKT pathway.Tumour Biol.2016378113651137410.1007/s13277‑016‑5013‑2 26960693
    [Google Scholar]
  83. ZhangH. ZhongX. ZhangX. ShangD. ZhouY. ZhangC. Enhanced anticancer effect of ABT-737 in combination with naringenin on gastric cancer cells.Exp. Ther. Med.201611266967310.3892/etm.2015.2912 26893664
    [Google Scholar]
  84. ShirakamiY. SakaiH. KochiT. SeishimaM. ShimizuM. Catechins and its role in chronic diseases.Drug Discovery from Mother Nature2016679010.1007/978‑3‑319‑41342‑6_4
    [Google Scholar]
  85. MoradzadehM. HosseiniA. ErfanianS. RezaeiH. Epigallocatechin-3-gallate promotes apoptosis in human breast cancer T47D cells through down-regulation of PI3K/AKT and Telomerase.Pharmacol. Rep.201769592492810.1016/j.pharep.2017.04.008 28646740
    [Google Scholar]
  86. ChenL. ZhangH.Y. Cancer preventive mechanisms of the green tea polyphenol (-)-epigallocatechin-3-gallate.Molecules200712594695710.3390/12050946 17873830
    [Google Scholar]
  87. LiuJ. XingJ. FeiY. Green tea (Camellia sinensis) and cancer prevention: A systematic review of randomized trials and epidemiological studies.Chin. Med.2008311210.1186/1749‑8546‑3‑12 18940008
    [Google Scholar]
  88. SutherlandB.A. RahmanR.M.A. AppletonI. Mechanisms of action of green tea catechins, with a focus on ischemia-induced neurodegeneration.J. Nutr. Biochem.200617529130610.1016/j.jnutbio.2005.10.005 16443357
    [Google Scholar]
  89. RanganathanS. HalagowderD. SivasithambaramN.D. Quercetin suppresses twist to induce apoptosis in MCF-7 breast cancer cells.PLoS One20151010e014137010.1371/journal.pone.0141370 26491966
    [Google Scholar]
  90. DuoJ. YingG.G. WangG.W. ZhangL. Quercetin inhibits human breast cancer cell proliferation and induces apoptosis via Bcl-2 and Bax regulation.Mol. Med. Rep.20125614531456 22447039
    [Google Scholar]
  91. ChouC.C. YangJ.S. LuH.F. IpS.W. LoC. WuC.C. LinJ.P. TangN.Y. ChungJ.G. ChouM.J. TengY.H. ChenD.R. Quercetin-mediated cell cycle arrest and apoptosis involving activation of a caspase cascade through the mitochondrial pathway in human breast cancer MCF-7 cells.Arch. Pharm. Res.20103381181119110.1007/s12272‑010‑0808‑y 20803121
    [Google Scholar]
  92. WangP. HeberD. HenningS.M. Quercetin increased the antiproliferative activity of green tea polyphenol (-)-epigallocatechin gallate in prostate cancer cells.Nutr. Cancer201264458058710.1080/01635581.2012.661514 22452782
    [Google Scholar]
  93. NiuG. YinS. XieS. LiY. NieD. MaL. WangX. WuY. Quercetin induces apoptosis by activating caspase-3 and regulating Bcl-2 and cyclooxygenase-2 pathways in human HL-60 cells.Acta Biochim. Biophys. Sin.2011431303710.1093/abbs/gmq107 21173056
    [Google Scholar]
  94. Granado-SerranoA.B. MartiínM.A. BravoL. GoyaL. RamosS. Quercetin induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI-3-kinase/Akt and ERK pathways in a human hepatoma cell line (HepG2).J. Nutr.2006136112715272110.1093/jn/136.11.2715 17056790
    [Google Scholar]
  95. SunS. GongF. LiuP. MiaoQ. Metformin combined with quercetin synergistically repressed prostate cancer cells via inhibition of VEGF/PI3K/Akt signaling pathway.Gene2018664505710.1016/j.gene.2018.04.045 29678660
    [Google Scholar]
  96. ImranM. RaufA. ShahZ.A. SaeedF. ImranA. ArshadM.U. AhmadB. BawazeerS. AtifM. PetersD.G. MubarakM.S. Chemo‐preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review.Phytother. Res.201933226327510.1002/ptr.6227 30402931
    [Google Scholar]
  97. LuoH. RankinG.O. LiZ. DePriestL. ChenY.C. Kaempferol induces apoptosis in ovarian cancer cells through activating p53 in the intrinsic pathway.Food Chem.2011128251351910.1016/j.foodchem.2011.03.073 21625365
    [Google Scholar]
  98. KashafiE. MoradzadehM. MohamadkhaniA. ErfanianS. Kaempferol increases apoptosis in human cervical cancer HeLa cells via PI3K/AKT and telomerase pathways.Biomed. Pharmacother.20178957357710.1016/j.biopha.2017.02.061 28258039
    [Google Scholar]
  99. DeanM. MurphyB.T. BurdetteJ.E. Phytosteroids beyond estrogens: Regulators of reproductive and endocrine function in natural products.Mol. Cell. Endocrinol.20174429810510.1016/j.mce.2016.12.013 27986590
    [Google Scholar]
  100. PandeyM. KaurP. ShuklaS. AbbasA. FuP. GuptaS. Plant flavone apigenin inhibits HDAC and remodels chromatin to induce growth arrest and apoptosis in human prostate cancer cells: In vitro and in vivo study.Mol. Carcinog.2012511295296210.1002/mc.20866 22006862
    [Google Scholar]
  101. ShuklaS. FuP. GuptaS. Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70–Bax interaction in prostate cancer.Apoptosis201419588389410.1007/s10495‑014‑0971‑6 24563225
    [Google Scholar]
  102. MengS. ZhuY. LiJ.F. WangX. LiangZ. LiS.Q. XuX. ChenH. LiuB. ZhengX.Y. XieL.P. Apigenin inhibits renal cell carcinoma cell proliferation.Oncotarget2017812198341984210.18632/oncotarget.15771 28423637
    [Google Scholar]
  103. GorlachS. FichnaJ. LewandowskaU. Polyphenols as mitochondria-targeted anticancer drugs.Cancer Lett.2015366214114910.1016/j.canlet.2015.07.004 26185003
    [Google Scholar]
  104. ImN.K. JangW.J. JeongC.H. JeongG.S. Delphinidin suppresses PMA-induced MMP-9 expression by blocking the NF-κB activation through MAPK signaling pathways in MCF-7 human breast carcinoma cells.J. Med. Food201417885586110.1089/jmf.2013.3077 25000305
    [Google Scholar]
  105. KlingenbergM. The ADP and ATP transport in mitochondria and its carrier.Biochim. Biophys. Acta Biomembr.20081778101978202110.1016/j.bbamem.2008.04.011
    [Google Scholar]
  106. HalestrapA.P. Dual role for the ADP/ATP translocator?Nature2004430700398398410.1038/nature02816 15332302
    [Google Scholar]
  107. OrtegaR. GarcíaN. The flavonoid quercetin induces changes in mitochondrial permeability by inhibiting adenine nucleotide translocase.J. Bioenerg. Biomembr.2009411414710.1007/s10863‑009‑9198‑6 19296209
    [Google Scholar]
  108. OishiM. IizumiY. TaniguchiT. GoiW. MikiT. SakaiT. Apigenin sensitizes prostate cancer cells to Apo2L/TRAIL by targeting adenine nucleotide translocase-2.PLoS One201382e5592210.1371/journal.pone.0055922 23431365
    [Google Scholar]
  109. MoiniH. ArroyoA. VayaJ. PackerL. Bioflavonoid effects on the mitochondrial respiratory electron transport chain and cytochrome c redox state.Redox Rep.199941-2354110.1179/135100099101534729 10714274
    [Google Scholar]
  110. SalviM. BrunatiA.M. ClariG. ToninelloA. Interaction of genistein with the mitochondrial electron transport chain results in opening of the membrane transition pore.Biochim. Biophys. Acta Bioenerg.200215562-318719610.1016/S0005‑2728(02)00361‑4 12460676
    [Google Scholar]
  111. ValentiD. de BariL. ManenteG.A. RossiL. MuttiL. MoroL. VaccaR.A. Negative modulation of mitochondrial oxidative phosphorylation by epigallocatechin-3 gallate leads to growth arrest and apoptosis in human malignant pleural mesothelioma cells.Biochim. Biophys. Acta Mol. Basis Dis.20131832122085209610.1016/j.bbadis.2013.07.014 23911347
    [Google Scholar]
  112. OliveiraM.R. NabaviS.F. DagliaM. RastrelliL. NabaviS.M. Epigallocatechin gallate and mitochondria—A story of life and death.Pharmacol. Res.2016104708510.1016/j.phrs.2015.12.027 26731017
    [Google Scholar]
  113. BendokasV. SkemieneK. TrumbeckaiteS. StanysV. PassamontiS. BorutaiteV. LiobikasJ. Anthocyanins: From plant pigments to health benefits at mitochondrial level.Crit. Rev. Food Sci. Nutr.202060193352336510.1080/10408398.2019.1687421 31718251
    [Google Scholar]
  114. LiobikasJ. SkemieneK. TrumbeckaiteS. BorutaiteV. Anthocyanins in cardioprotection: A path through mitochondria. Pharmacol. Res.2016113Pt B80881510.1016/j.phrs.2016.03.036 27038533
    [Google Scholar]
  115. WangJ. FangF. HuangZ. WangY. WongC. Kaempferol is an estrogen‐related receptor α and γ inverse agonist.FEBS Lett.2009583464364710.1016/j.febslet.2009.01.030 19171140
    [Google Scholar]
  116. BussG.D. ConstantinJ. de LimaL.C. TeodoroG.R. ComarJ.F. Ishii-IwamotoE.L. BrachtA. The action of quercetin on the mitochondrial NADH to NAD(+) ratio in the isolated perfused rat liver.Planta Med.200571121118112210.1055/s‑2005‑873174 16395647
    [Google Scholar]
  117. ConstantinR.P. NascimentoG.S. ConstantinR.P. SalgueiroC.L. BrachtA. Ishii-IwamotoE.L. YamamotoN.S. ConstantinJ. Citrus flavanones affect hepatic fatty acid oxidation in rats by acting as prooxidant agents.BioMed Res. Int.2013201311210.1155/2013/342973 24288675
    [Google Scholar]
  118. ChenL.B. Mitochondrial membrane potential in living cells.Annu. Rev. Cell Biol.19884115518110.1146/annurev.cb.04.110188.001103 3058159
    [Google Scholar]
  119. FantinV.R. St-PierreJ. LederP. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance.Cancer Cell20069642543410.1016/j.ccr.2006.04.023 16766262
    [Google Scholar]
  120. BernatonieneJ. KopustinskieneD. JakstasV. MajieneD. BanieneR. KuršvietieneL. MasteikovaR. SavickasA. ToleikisA. TrumbeckaiteS. The effect of Leonurus cardiaca herb extract and some of its flavonoids on mitochondrial oxidative phosphorylation in the heart.Planta Med.201480752553210.1055/s‑0034‑1368426 24841965
    [Google Scholar]
  121. BernatonieneJ. TrumbeckaiteS. MajieneD. BanieneR. BaliutyteG. SavickasA. ToleikisA. The effect of crataegus fruit extract and some of its flavonoids on mitochondrial oxidative phosphorylation in the heart.Phytother. Res.200923121701170710.1002/ptr.2815 19441016
    [Google Scholar]
  122. KopustinskieneD.M. SavickasA. VetchýD. MasteikovaR. KasauskasA. BernatonieneJ. Direct effects of (-)-epicatechin and procyanidin B2 on the respiration of rat heart mitochondria.BioMed Res. Int.201520151710.1155/2015/232836 25811024
    [Google Scholar]
  123. RavanelP. Uncoupling activity of a series of flavones and flavonols on isolated plant mitochondria.Phytochemistry19862551015102010.1016/S0031‑9422(00)81546‑0
    [Google Scholar]
  124. van DijkC. DriessenA.J.M. RecourtK. The uncoupling efficiency and affinity of flavonoids for vesicles.Biochem. Pharmacol.200060111593160010.1016/S0006‑2952(00)00488‑3 11077041
    [Google Scholar]
  125. DortaD.J. PigosoA.A. MingattoF.E. RodriguesT. PradoI.M.R. HelenaA.F.C. UyemuraS.A. SantosA.C. CurtiC. The interaction of flavonoids with mitochondria: Effects on energetic processes.Chem. Biol. Interact.20051522-3677810.1016/j.cbi.2005.02.004 15840381
    [Google Scholar]
  126. OteizaP.I. FragaC.G. MillsD.A. TaftD.H. Flavonoids and the gastrointestinal tract: Local and systemic effects.Mol. Aspects Med.201861414910.1016/j.mam.2018.01.001 29317252
    [Google Scholar]
  127. WellsJ.M. BrummerR.J. DerrienM. MacDonaldT.T. TroostF. CaniP.D. TheodorouV. DekkerJ. MéheustA. de VosW.M. MercenierA. NautaA. Garcia-RodenasC.L. Homeostasis of the gut barrier and potential biomarkers.Am. J. Physiol. Gastrointest. Liver Physiol.20173123G171G19310.1152/ajpgi.00048.2015 27908847
    [Google Scholar]
  128. RowlandI. GibsonG. HeinkenA. ScottK. SwannJ. ThieleI. TuohyK. Gut microbiota functions: Metabolism of nutrients and other food components.Eur. J. Nutr.201857112410.1007/s00394‑017‑1445‑8 28393285
    [Google Scholar]
  129. QuG. ChenJ. GuoX. The beneficial and deleterious role of dietary polyphenols on chronic degenerative diseases by regulating gene expression.Biosci. Trends201812652653610.5582/bst.2018.01172 30606977
    [Google Scholar]
  130. EspínJ.C. González-SarríasA. Tomás-BarberánF.A. The gut microbiota: A key factor in the therapeutic effects of (poly)phenols.Biochem. Pharmacol.2017139829310.1016/j.bcp.2017.04.033 28483461
    [Google Scholar]
  131. BettaiebA. Vazquez PrietoM.A. Rodriguez LanziC. MiatelloR.M. HajF.G. FragaC.G. OteizaP.I. (−)-Epicatechin mitigates high-fructose-associated insulin resistance by modulating redox signaling and endoplasmic reticulum stress.Free Radic. Biol. Med.20147224725610.1016/j.freeradbiomed.2014.04.011 24746618
    [Google Scholar]
  132. Gutiérrez-SalmeánG. Ortiz-VilchisP. VacaseydelC.M. Garduño-SicilianoL. Chamorro-CevallosG. MeaneyE. VillafañaS. VillarrealF. CeballosG. Ramírez-SánchezI. Effects of (−)-epicatechin on a diet-induced rat model of cardiometabolic risk factors.Eur. J. Pharmacol.2014728243010.1016/j.ejphar.2014.01.053 24491839
    [Google Scholar]
  133. Vazquez PrietoM.A. BettaiebA. Rodriguez LanziC. SotoV.C. PerdicaroD.J. GalmariniC.R. HajF.G. MiatelloR.M. OteizaP.I. Catechin and quercetin attenuate adipose inflammation in fructose‐fed rats and 3T3‐L1 adipocytes.Mol. Nutr. Food Res.201559462263310.1002/mnfr.201400631 25620282
    [Google Scholar]
  134. CremoniniE. MastaloudisA. HesterS.N. VerstraetenS.V. AndersonM. WoodS.M. WaterhouseA.L. FragaC.G. OteizaP.I. Anthocyanins inhibit tumor necrosis alpha-induced loss of Caco-2 cell barrier integrity.Food Funct.2017882915292310.1039/C7FO00625J 28740990
    [Google Scholar]
  135. OlejnikA. KowalskaK. KidońM. CzapskiJ. RychlikJ. OlkowiczM. DembczyńskiR. Purple carrot anthocyanins suppress lipopolysaccharide-induced inflammation in the co-culture of intestinal Caco-2 and macrophage RAW264.7 cells.Food Funct.20167155756410.1039/C5FO00890E 26613574
    [Google Scholar]
  136. HeX. SunL. Dietary intake of flavonoid subclasses and risk of colorectal cancer: Evidence from population studies.Oncotarget2016718266172662710.18632/oncotarget.8562 27058896
    [Google Scholar]
  137. GrossoG. GodosJ. Lamuela-RaventosR. RayS. MicekA. PajakA. SciaccaS. D’OrazioN. Del RioD. GalvanoF. A comprehensive meta‐analysis on dietary flavonoid and lignan intake and cancer risk: Level of evidence and limitations.Mol. Nutr. Food Res.2017614160093010.1002/mnfr.201600930 27943649
    [Google Scholar]
  138. RossiM. BosettiC. NegriE. LagiouP. VecchiaC.L. Flavonoids, proanthocyanidins, and cancer risk: A network of case-control studies from Italy.Nutr. Cancer201062787187710.1080/01635581.2010.509534 20924962
    [Google Scholar]
  139. LiY. ZhangT. ChenG. Flavonoids and colorectal cancer prevention.Antioxidants201871218710.3390/antiox7120187 30544686
    [Google Scholar]
  140. MasumotoS. TeraoA. YamamotoY. MukaiT. MiuraT. ShojiT. Non-absorbable apple procyanidins prevent obesity associated with gut microbial and metabolomic changes.Sci. Rep.2016613120810.1038/srep31208 27506289
    [Google Scholar]
  141. SugiyamaH. AkazomeY. ShojiT. YamaguchiA. YasueM. KandaT. OhtakeY. Oligomeric procyanidins in apple polyphenol are main active components for inhibition of pancreatic lipase and triglyceride absorption.J. Agric. Food Chem.200755114604460910.1021/jf070569k 17458979
    [Google Scholar]
  142. FeiQ. GaoY. ZhangX. SunY. HuB. ZhouL. JabbarS. ZengX. Effects of Oolong tea polyphenols, EGCG, and EGCG3″Me on pancreatic α-amylase activity in vitro.J. Agric. Food Chem.201462399507951410.1021/jf5032907 25222598
    [Google Scholar]
  143. CardonaF. Andrés-LacuevaC. TulipaniS. TinahonesF.J. Queipo-OrtuñoM.I. Benefits of polyphenols on gut microbiota and implications in human health.J. Nutr. Biochem.20132481415142210.1016/j.jnutbio.2013.05.001 23849454
    [Google Scholar]
  144. DavidL.A. MauriceC.F. CarmodyR.N. GootenbergD.B. ButtonJ.E. WolfeB.E. LingA.V. DevlinA.S. VarmaY. FischbachM.A. BiddingerS.B. DuttonR.J. TurnbaughP.J. Diet rapidly and reproducibly alters the human gut microbiome.Nature2014505748455956310.1038/nature12820 24336217
    [Google Scholar]
  145. MarchesiJ.R. AdamsD.H. FavaF. HermesG.D.A. HirschfieldG.M. HoldG. QuraishiM.N. KinrossJ. SmidtH. TuohyK.M. ThomasL.V. ZoetendalE.G. HartA. The gut microbiota and host health: A new clinical frontier.Gut201665233033910.1136/gutjnl‑2015‑309990 26338727
    [Google Scholar]
  146. WalleT. Absorption and metabolism of flavonoids.Free Radic. Biol. Med.200436782983710.1016/j.freeradbiomed.2004.01.002 15019968
    [Google Scholar]
  147. CassidyA. MinihaneA.M. The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids.Am. J. Clin. Nutr.20171051102210.3945/ajcn.116.136051 27881391
    [Google Scholar]
  148. WilliamsonG. CliffordM.N. Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols.Biochem. Pharmacol.2017139243910.1016/j.bcp.2017.03.012 28322745
    [Google Scholar]
  149. Duda-ChodakA. The inhibitory effect of polyphenols on human gut microbiota.J. Physiol. Pharmacol.2012635497503 23211303
    [Google Scholar]
  150. NohynekL.J. AlakomiH.L. KähkönenM.P. HeinonenM. HelanderI.M. Oksman-CaldenteyK.M. Puupponen-PimiäR.H. Berry phenolics: Antimicrobial properties and mechanisms of action against severe human pathogens.Nutr. Cancer2006541183210.1207/s15327914nc5401_4 16800770
    [Google Scholar]
  151. EspleyR.V. ButtsC.A. LaingW.A. MartellS. SmithH. McGhieT.K. ZhangJ. PaturiG. HedderleyD. BovyA. SchoutenH.J. PutterillJ. AllanA.C. HellensR.P. Dietary flavonoids from modified apple reduce inflammation markers and modulate gut microbiota in mice.J. Nutr.2014144214615410.3945/jn.113.182659 24353343
    [Google Scholar]
  152. GwiazdowskaD. JuśK. Jasnowska-MałeckaJ. KluczyńskaK. The impact of polyphenols on Bifidobacterium growth.Acta Biochim. Pol.201562489590110.18388/abp.2015_1154 26619254
    [Google Scholar]
  153. RidlonJ.M. KangD.J. HylemonP.B. BajajJ.S. Bile acids and the gut microbiome.Curr. Opin. Gastroenterol.201430333233810.1097/MOG.0000000000000057 24625896
    [Google Scholar]
  154. MaynardC.L. ElsonC.O. HattonR.D. WeaverC.T. Reciprocal interactions of the intestinal microbiota and immune system.Nature2012489741523124110.1038/nature11551 22972296
    [Google Scholar]
  155. ShorttC. HasselwanderO. MeynierA. NautaA. FernándezE.N. PutzP. RowlandI. SwannJ. TürkJ. VermeirenJ. AntoineJ.M. Systematic review of the effects of the intestinal microbiota on selected nutrients and non-nutrients.Eur. J. Nutr.2018571254910.1007/s00394‑017‑1546‑4 29086061
    [Google Scholar]
  156. KuoS.M. Dietary flavonoid and cancer prevention: evidence and potential mechanism.Crit. Rev. Oncog.199781476910.1615/CritRevOncog.v8.i1.30
    [Google Scholar]
  157. GalatiG. O’BrienP.J. Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties.Free Radic. Biol. Med.200437328730310.1016/j.freeradbiomed.2004.04.034 15223063
    [Google Scholar]
  158. SkibolaC.F. SmithM.T. Potential health impacts of excessive flavonoid intake.Free Radic. Biol. Med.2000293-437538310.1016/S0891‑5849(00)00304‑X 11035267
    [Google Scholar]
  159. GuptaS.C. KunnumakkaraA.B. AggarwalS. AggarwalB.B. Inflammation, a double-edge sword for cancer and other age-related diseases.Front. Immunol.20189216010.3389/fimmu.2018.02160 30319623
    [Google Scholar]
  160. Pérez-CanoF. CastellM. Flavonoids, inflammation and immune system.Nutrients201681065910.3390/nu8100659 27775647
    [Google Scholar]
  161. DingS. JiangH. FangJ. Regulation of immune function by polyphenols.J. Immunol. Res.201812126407410.1155/2018/1264074
    [Google Scholar]
  162. HosseinzadeA. SadeghiO. Naghdipour BireganiA. SoukhtehzariS. BrandtG.S. EsmaillzadehA. Immunomodulatory effects of flavonoids: Possible induction of T CD4+ regulatory cells through suppression of mTOR pathway signaling activity.Front. Immunol.2019105110.3389/fimmu.2019.00051 30766532
    [Google Scholar]
  163. MooradianM.J. SullivanR.J. Immunomodulatory effects of current cancer treatment and the consequences for follow-up immunotherapeutics.Future Oncol.201713181649166310.2217/fon‑2017‑0117 28776423
    [Google Scholar]
  164. XuL. ZhangY. TianK. ChenX. ZhangR. MuX. WuY. WangD. WangS. LiuF. WangT. ZhangJ. LiuS. ZhangY. TuC. LiuH. Apigenin suppresses PD-L1 expression in melanoma and host dendritic cells to elicit synergistic therapeutic effects.J. Exp. Clin. Cancer Res.201837126110.1186/s13046‑018‑0929‑6 30373602
    [Google Scholar]
  165. LiW. KimT.I. KimJ.H. ChungH.S. Immune checkpoint PD-1/PD-L1 CTLA-4/CD80 are blocked by Rhus verniciflua Stokes and its active compounds.Molecules20192422406210.3390/molecules24224062 31717574
    [Google Scholar]
  166. BaoF. BaiH.Y. WuZ.R. YangZ.G. Phenolic compounds from cultivated Glycyrrhiza uralensis and their PD-1/PD-L1 inhibitory activities.Nat. Prod. Res.202135456256910.1080/14786419.2019.1586698 30908097
    [Google Scholar]
  167. SundaramM.K. UnniS. SomvanshiP. BhardwajT. MandalR.K. HussainA. HaqueS. Genistein modulates signaling pathways and targets several epigenetic markers in HeLa cells.Genes2019101295510.3390/genes10120955 31766427
    [Google Scholar]
  168. PonsD.G. Vilanova-LlompartJ. Gaya-BoverA. Alorda-ClaraM. OliverJ. RocaP. Sastre-SerraJ. The phytoestrogen genistein affects inflammatory-related genes expression depending on the ERα/ERβ ratio in breast cancer cells.Int. J. Food Sci. Nutr.201970894194910.1080/09637486.2019.1597025 30945577
    [Google Scholar]
  169. LiskovaA. KubatkaP. SamecM. ZuborP. MlyncekM. BielikT. SamuelS.M. ZulliA. KwonT.K. BüsselbergD. Dietary phytochemicals targeting cancer stem cells.Molecules201924589910.3390/molecules24050899 30836718
    [Google Scholar]
  170. SakamotoY. KanatsuJ. TohM. NakaA. KondoK. IidaK. The dietary isoflavone daidzein reduces expression of pro-inflammatory genes through PPARα/γ and JNK pathways in adipocyte and macrophage co-cultures.PLoS One2016112e014967610.1371/journal.pone.0149676 26901838
    [Google Scholar]
  171. RenH. HaoJ. LiuT. ZhangD. LvH. SongE. ZhuC. Hesperetin suppresses inflammatory responses in lipopolysaccharide-induced RAW 264.7 cells via the inhibition of NF-κB and activation of Nrf2/HO-1 pathways.Inflammation201639396497310.1007/s10753‑016‑0311‑9 26994999
    [Google Scholar]
  172. NaliniN. AranganathanS. KabalimurthyJ. Chemopreventive efficacy of hesperetin (citrus flavonone) against 1,2-dimethylhydrazine-induced rat colon carcinogenesis.Toxicol. Mech. Methods201222539740810.3109/15376516.2012.673092 22409373
    [Google Scholar]
  173. AhmedO.M. AhmedA.A. FahimH.I. ZakyM.Y. Quercetin and naringenin abate diethylnitrosamine/acetylaminofluorene-induced hepatocarcinogenesis in Wistar rats: The roles of oxidative stress, inflammation and cell apoptosis.Drug Chem. Toxicol.202245126227310.1080/01480545.2019.1683187 31665932
    [Google Scholar]
  174. ZhaoZ. JinG. GeY. GuoZ. Naringenin inhibits migration of breast cancer cells via inflammatory and apoptosis cell signaling pathways.Inflammopharmacology20192751021103610.1007/s10787‑018‑00556‑3 30941613
    [Google Scholar]
  175. ChenY.Y. ChangY.M. WangK.Y. ChenP.N. HseuY.C. ChenK.M. YehK.T. ChenC.J. HsuL.S. Naringenin inhibited migration and invasion of glioblastoma cells through multiple mechanisms.Environ. Toxicol.201934323323910.1002/tox.22677 30431227
    [Google Scholar]
  176. ShirakamiY. SakaiH. KochiT. SeishimaM. ShimizuM. Catechins and its role in chronic diseases.Drug Discovery from Mother Nature2016679010.1007/978‑3‑319‑41342‑6_4
    [Google Scholar]
  177. Granado-SerranoA.B. MartínM.A. HaegemanG. GoyaL. BravoL. RamosS. Epicatechin induces NF-κB, activator protein-1 (AP-1) and nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) via phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) signalling in HepG2 cells.Br. J. Nutr.2010103216817910.1017/S0007114509991747 20030899
    [Google Scholar]
  178. LiuY. TangZ.G. LinY. QuX.G. LvW. WangG.B. LiC.L. Effects of quercetin on proliferation and migration of human glioblastoma U251 cells.Biomed. Pharmacother.201792333810.1016/j.biopha.2017.05.044 28528183
    [Google Scholar]
  179. MauryaA.K. VinayakM. Quercetin attenuates cell survival, inflammation, and angiogenesis via modulation of AKT signaling in murine T-cell lymphoma.Nutr. Cancer201769347048010.1080/01635581.2017.1267775 28107044
    [Google Scholar]
  180. SongY. HanM. ZhangX. Quercetin suppresses the migration and invasion in human colon cancer Caco-2 cells through regulating toll-like receptor 4/Nuclear Factor-kappa B pathway.Pharmacogn. Mag.2016124623710.4103/0973‑1296.182154 27279714
    [Google Scholar]
  181. BruningA. Inhibition of mTOR signaling by quercetin in cancer treatment and prevention. Anti-Can.Agents Med. Chem.20131371025103110.2174/18715206113139990114
    [Google Scholar]
  182. LeeS.H. KimY.J. KwonS.H. LeeY.H. ChoiS.Y. ParkJ.S. KwonH.J. Inhibitory effects of flavonoids on TNF-α-induced IL-8 gene expression in HEK 293 cells.BMB Rep.200942526527010.5483/BMBRep.2009.42.5.265 19470239
    [Google Scholar]
  183. RenJ. LuY. QianY. ChenB. WuT. JiG. Recent progress regarding kaempferol for the treatment of various diseases (Review).Exp. Ther. Med.20191842759277610.3892/etm.2019.7886 31572524
    [Google Scholar]
  184. DeviK.P. MalarD.S. NabaviS.F. SuredaA. XiaoJ. NabaviS.M. DagliaM. Kaempferol and inflammation: From chemistry to medicine.Pharmacol. Res.20159911010.1016/j.phrs.2015.05.002 25982933
    [Google Scholar]
  185. KadiogluO. NassJ. SaeedM.E. SchulerB. EfferthT. Kaempferol is an anti-inflammatory compound with activity towards NF-κB pathway proteins.Anticancer Res.201535526452650 25964540
    [Google Scholar]
  186. GhițuA. SchwiebsA. RadekeH.H. AvramS. ZupkoI. BorA. PavelI.Z. DeheleanC.A. OpreanC. BojinF. FarcasC. SoicaC. DuicuO. DanciuC. A comprehensive assessment of apigenin as an antiproliferative, proapoptotic, antiangiogenic and immunomodulatory phytocompound.Nutrients201911485810.3390/nu11040858 30995771
    [Google Scholar]
  187. AiX.Y. QinY. LiuH.J. CuiZ.H. LiM. YangJ.H. ZhongW.L. LiuY.R. ChenS. SunT. ZhouH.G. YangC. Apigenin inhibits colonic inflammation and tumorigenesis by suppressing STAT3-NF-κB signaling.Oncotarget201785910021610022610.18632/oncotarget.22145 29245972
    [Google Scholar]
  188. RehmanM.U. TahirM. KhanA.Q. KhanR. LateefA. Oday-O-Hamiza; Qamar, W.; Ali, F.; Sultana, S. Chrysin suppresses renal carcinogenesis via amelioration of hyperproliferation, oxidative stress and inflammation: Plausible role of NF-κB.Toxicol. Lett.20132162-314615810.1016/j.toxlet.2012.11.013 23194824
    [Google Scholar]
  189. UllahA. MunirS. BadshahS.L. KhanN. GhaniL. PoulsonB.G. EmwasA.H. JaremkoM. Important flavonoids and their role as a therapeutic agent.Molecules20202522524310.3390/molecules25225243 33187049
    [Google Scholar]
  190. RenL.Q. LiQ. ZhangY. Luteolin suppresses the proliferation of gastric cancer cells and acts in synergy with oxaliplatin.BioMed Res. Int.202020201910.1155/2020/9396512 32149146
    [Google Scholar]
  191. ImranM. SalehiB. Sharifi-RadJ. Aslam GondalT. SaeedF. ImranA. ShahbazM. Tsouh FokouP.V. Umair ArshadM. KhanH. GuerreiroS.G. MartinsN. EstevinhoL.M. Kaempferol: A key emphasis to its anticancer potential.Molecules20192412227710.3390/molecules24122277 31248102
    [Google Scholar]
  192. AshrafizadehM. BakhodaM.R. BahmanpourZ. IlkhaniK. ZarrabiA. MakvandiP. KhanH. MazaheriS. DarvishM. MirzaeiH. Apigenin as tumor suppressor in cancers: Biotherapeutic activity, nanodelivery, and mechanisms with emphasis on pancreatic cancer.Front Chem.2020882910.3389/fchem.2020.00829 33195038
    [Google Scholar]
  193. DharmawansaK.V.S. HoskinD.W. RupasingheH.P.V. Chemopreventive effect of dietary anthocyanins against gastrointestinal cancers: A review of recent advances and perspectives.Int. J. Mol. Sci.20202118655510.3390/ijms21186555 32911639
    [Google Scholar]
  194. SpagnuoloC. RussoG.L. OrhanI.E. HabtemariamS. DagliaM. SuredaA. NabaviS.F. DeviK.P. LoizzoM.R. TundisR. NabaviS.M. Genistein and cancer: Current status, challenges, and future directions.Adv. Nutr.20156440841910.3945/an.114.008052 26178025
    [Google Scholar]
  195. YapK.M. SekarM. WuY.S. GanS.H. RaniN.N.I.M. SeowL.J. SubramaniyanV. FuloriaN.K. FuloriaS. LumP.T. Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects.Saudi J. Biol. Sci.202128126730674710.1016/j.sjbs.2021.07.046 34866972
    [Google Scholar]
  196. AboulaghrasS. SahibN. BakrimS. BenaliT. CharfiS. GuaouguaouF.E. OmariN.E. GalloM. MontesanoD. ZenginG. TaghzoutiK. BouyahyaA. Health benefits and pharmacological aspects of chrysoeriol.Pharmaceuticals202215897310.3390/ph15080973 36015121
    [Google Scholar]
  197. WangZ. LvJ. LiX. LinQ. The flavonoid Astragalin shows anti‐tumor activity and inhibits PI3K/AKT signaling in gastric cancer.Chem. Biol. Drug Des.202198577978610.1111/cbdd.13933 34396710
    [Google Scholar]
  198. YeB. MaJ. LiZ. LiY. HanX. Ononin shows anticancer activity against laryngeal cancer via the inhibition of ERK/JNK/p38 signaling pathway.Front. Oncol.20221293964610.3389/fonc.2022.939646 35912256
    [Google Scholar]
  199. VermaE. KumarA. Devi DaimaryU. ParamaD. GirisaS. SethiG. KunnumakkaraA.B. Potential of baicalein in the prevention and treatment of cancer: A scientometric analyses based review.J. Funct. Foods20218610466010.1016/j.jff.2021.104660
    [Google Scholar]
  200. NingR. ChenG. FangR. ZhangY. ZhaoW. QianF. Diosmetin inhibits cell proliferation and promotes apoptosis through STAT3/c-Myc signaling pathway in human osteosarcoma cells.Biol. Res.20215414010.1186/s40659‑021‑00363‑1 34922636
    [Google Scholar]
  201. RazaW. LuqmanS. MeenaA. Prospects of tangeretin as a modulator of cancer targets/pathways.Pharmacol. Res.202016110520210.1016/j.phrs.2020.105202 32942013
    [Google Scholar]
  202. LiY. YuH. HanF. WangM. LuoY. GuoX. Biochanin A induces S phase arrest and apoptosis in lung cancer cells.BioMed Res. Int.2018201811210.1155/2018/3545376 30402472
    [Google Scholar]
  203. NooriS. Rezaei TaviraniM. DeraviN. Mahboobi RabbaniM.I. ZarghiA. Naringenin enhances the anti-cancer effect of cyclophosphamide against MDA-MB-231 breast cancer cells via targeting the STAT3 signaling pathway.Iran. J. Pharm. Res.2020193122133 33680016
    [Google Scholar]
  204. DebnathS. SarkarA. MukherjeeD.D. RayS. MahataB. MahataT. ParidaP.K. DasT. MukhopadhyayR. GhoshZ. BiswasK. Eriodictyol mediated selective targeting of the TNFR1/FADD/TRADD axis in cancer cells induce apoptosis and inhibit tumor progression and metastasis.Transl. Oncol.20222110143310.1016/j.tranon.2022.101433 35462210
    [Google Scholar]
  205. ZhuX. LiR. WangC. ZhouS. FanY. MaS. GaoD. GaiN. YangJ. Pinocembrin inhibits the proliferation and metastasis of breast cancer via suppression of the PI3K/AKT signaling pathway.Front. Oncol.20211166118410.3389/fonc.2021.661184 34336656
    [Google Scholar]
  206. ChoE. ChungE.Y. JangH.Y. HongO.Y. ChaeH.S. JeongY.J. KimS.Y. KimB.S. YooD.J. KimJ.S. ParkK.H. Anti-cancer effect of cyanidin-3-glucoside from mulberry via caspase-3 cleavage and DNA fragmentation in vitro and in vivo. Anti-Can Agents.Med. Chem.201717111519152510.2174/1871520617666170327152026
    [Google Scholar]
  207. SharmaA. ChoiH.K. KimY.K. LeeH.J. Delphinidin and Its Glycosides’ War on Cancer: Preclinical Perspectives.Int. J. Mol. Sci.202122211150010.3390/ijms222111500 34768930
    [Google Scholar]
  208. YaoL. LiuW. BashirM. NisarM.F. WanC.C. Eriocitrin: A review of pharmacological effects.Biomed. Pharmacother.202215411356310.1016/j.biopha.2022.113563 35987162
    [Google Scholar]
  209. LiS. LiW. WangC. WuR. YinR. KuoH.C. WangL. KongA.N. Pelargonidin reduces the TPA induced transformation of mouse epidermal cells –potential involvement of Nrf2 promoter demethylation.Chem. Biol. Interact.201930910870110.1016/j.cbi.2019.06.014 31181187
    [Google Scholar]
  210. MaY. LiY. ZhangH. WangY. WuC. HuangW. Malvidin induces hepatic stellate cell apoptosis via the endoplasmic reticulum stress pathway and mitochondrial pathway.Food Sci. Nutr.2020895095510610.1002/fsn3.1810 32994970
    [Google Scholar]
  211. MishraP.K. ShandilyaR. BhargavaA. SamarthR.M. TiwariR. MishraD.K. SrivastavaR.K. SharmaR.S. LohiyaN.K. MishraP.K. Nano-engineered flavonoids for cancer protection.Front. Biosci.20192461097115710.2741/4771 30844733
    [Google Scholar]
  212. AmawiH. AshbyC.R.Jr TiwariA.K. Cancer chemoprevention through dietary flavonoids: what’s limiting?Chin. J. Cancer20173615010.1186/s40880‑017‑0217‑4 28061892
    [Google Scholar]
  213. GaoS. HuM. Bioavailability challenges associated with development of anti-cancer phenolics.Mini Rev. Med. Chem.201010655056710.2174/138955710791384081 20370701
    [Google Scholar]
  214. Palafox-CarlosH. Ayala-ZavalaJ.F. González-AguilarG.A. The role of dietary fiber in the bioaccessibility and bioavailability of fruit and vegetable antioxidants.J. Food Sci.2011761R6R1510.1111/j.1750‑3841.2010.01957.x 21535705
    [Google Scholar]
  215. RuenroengklinN. ZhongJ. DuanX. YangB. LiJ. JiangY. Effects of various temperatures and pH values on the extraction yield of phenolics from litchi fruit pericarp tissue and the antioxidant activity of the extracted anthocyanins.Int. J. Mol. Sci.2008971333134110.3390/ijms9071333 19325806
    [Google Scholar]
  216. SchubertW. ErikssonU. EdgarB. CullbergG. HednerT. Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17β-estradiol.Eur. J. Drug Metab. Pharmacokinet.199520321922410.1007/BF03189673 8751044
    [Google Scholar]
  217. ChenZ. ZhengS. LiL. JiangH. Metabolism of flavonoids in human: A comprehensive review.Curr. Drug Metab.2014151486110.2174/138920021501140218125020 24588554
    [Google Scholar]
  218. XiaoJ. Dietary flavonoid aglycones and their glycosides: Which show better biological significance?Crit. Rev. Food Sci. Nutr.201757918741905 26176651
    [Google Scholar]
  219. KolahalamL.A. Kasi ViswanathI.V. DiwakarB.S. GovindhB. ReddyV. MurthyY.L.N. Review on nanomaterials: Synthesis and applications.Mater. Today Proc.2019182182219010.1016/j.matpr.2019.07.371
    [Google Scholar]
  220. ZhangZ. WangJ. ChenC. Near-infrared light-mediated nanoplatforms for cancer thermo-chemotherapy and optical imaging.Adv. Mater.201325283869388010.1002/adma.201301890 24048973
    [Google Scholar]
  221. ZhangZ. WangJ. NieX. WenT. JiY. WuX. ZhaoY. ChenC. Near infrared laser-induced targeted cancer therapy using thermoresponsive polymer encapsulated gold nanorods.J. Am. Chem. Soc.2014136207317732610.1021/ja412735p 24773323
    [Google Scholar]
  222. ShiJ. KantoffP.W. WoosterR. FarokhzadO.C. Cancer nanomedicine: Progress, challenges and opportunities.Nat. Rev. Cancer2017171203710.1038/nrc.2016.108 27834398
    [Google Scholar]
  223. MuL.M. JuR.J. LiuR. BuY.Z. ZhangJ.Y. LiX.Q. ZengF. LuW.L. Dual-functional drug liposomes in treatment of resistant cancers.Adv. Drug Deliv. Rev.2017115465610.1016/j.addr.2017.04.006 28433739
    [Google Scholar]
  224. SunL. WuQ. PengF. LiuL. GongC. Strategies of polymeric nanoparticles for enhanced internalization in cancer therapy.Colloids Surf. B Biointerfaces2015135567210.1016/j.colsurfb.2015.07.013 26241917
    [Google Scholar]
  225. ParkJ.W. Liposome-based drug delivery in breast cancer treatment.Breast Cancer Res.200243959910.1186/bcr432 12052251
    [Google Scholar]
  226. FengL. ChengL. DongZ. TaoD. BarnhartT.E. CaiW. ChenM. LiuZ. Theranostic liposomes with hypoxia-activated prodrug to effectively destruct hypoxic tumors post-photodynamic therapy.ACS Nano201711192793710.1021/acsnano.6b07525 28027442
    [Google Scholar]
  227. WangY. XieY. LiJ. PengZ.H. SheininY. ZhouJ. OupickýD. Tumor-penetrating nanoparticles for enhanced anticancer activity of combined photodynamic and hypoxia-activated therapy.ACS Nano20171122227223810.1021/acsnano.6b08731 28165223
    [Google Scholar]
  228. LiuY. LiuY. BuW. ChengC. ZuoC. XiaoQ. SunY. NiD. ZhangC. LiuJ. ShiJ. Hypoxia induced by upconversion‐based photodynamic therapy: towards highly effective synergistic bioreductive therapy in tumors.Angew. Chem. Int. Ed.201554288105810910.1002/anie.201500478 26012928
    [Google Scholar]
  229. WuH. HuangX. GaoM. LiaoX. ShiB. Polyphenol-grafted collagen fiber as reductant and stabilizer for one-step synthesis of size-controlled gold nanoparticles and their catalytic application to 4-nitrophenol reduction.Green Chem.201113365165810.1039/c0gc00843e
    [Google Scholar]
  230. LeZ. ChenY. HanH. TianH. ZhaoP. YangC. HeZ. LiuL. LeongK.W. MaoH.Q. LiuZ. ChenY. Hydrogen-bonded tannic acid-based anticancer nanoparticle for enhancement of oral chemotherapy.ACS Appl. Mater. Interfaces20181049421864219710.1021/acsami.8b18979 30444601
    [Google Scholar]
  231. WangX. YanJ. PanD. YangR. WangL. XuY. ShengJ. YueY. HuangQ. WangY. WangR. YangM. Polyphenol–poloxamer self‐assembled supramolecular nanoparticles for tumor NIRF/PET imaging.Adv. Healthc. Mater.2018715170150510.1002/adhm.201701505 29761649
    [Google Scholar]
  232. SinghS. AhujaA. SharmaH. MaheshwariP. An overview of dietary flavonoids as a nutraceutical nanoformulation approach to life-threatening diseases.Curr. Pharm. Biotechnol.202324141740177310.2174/1389201024666230314101654 36918792
    [Google Scholar]
/content/journals/cpb/10.2174/0113892010297456240327062614
Loading
/content/journals/cpb/10.2174/0113892010297456240327062614
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keyword(s): Cancer; cell proliferation; flavonoids; gut microbiota; oxidant; reactive oxygen species
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test