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2000
Volume 24, Issue 1
  • ISSN: 1871-5230
  • E-ISSN: 1875-614X

Abstract

Background

Inflammatory, immune, and neurodegenerative diseases constitute a category of persistent and debilitating conditions affecting millions worldwide, with intertwined pathophysiological pathways. Recent research has spotlighted naturally occurring compounds like naringenin for potential therapeutic applications across multiple ailments.

Objectives

This review offers an encompassing exploration of naringenin's anti-inflammatory, immune-protective, and neuroprotective mechanisms, elucidating its pharmacological targets, signal transduction pathways, safety profile, and insights from clinical investigations.

Methods

Data for this review were amassed through the scrutiny of various published studies search engines such as PubMed and Google Scholar. Content from reputable publishers including Bentham Science, Taylor and Francis, Nature, PLOS ONE, among others, was referenced.

Results

Naringenin exhibits substantial anti-inflammatory effects by restraining the NF-κB signaling pathway. It activates Nrf2, renowned for its anti-inflammatory properties, inducing the release of hemeoxynase-1 by macrophages. Furthermore, naringenin treatment downregulates the expression of Th1 cytokines and inflammatory mediators. It also impedes xanthine oxidase, counteracts reactive oxygen species (ROS), scavenges superoxide radicals, mitigates the accessibility of oxygen-induced K+ erythrocytes, and reduces lipid peroxidation. Naringenin's antioxidant prowess holds promise for addressing neurological conditions.

Conclusion

Extensive research has been undertaken to establish the anti-inflammatory, immunomodulatory, and neuroprotective attributes of naringenin across various medical domains, lending credence to its pharmacological utility. The principal obstacle to naringenin's adoption as a therapeutic agent remains the dearth of data. Efforts should focus on rendering naringenin delivery patient-friendly, economically viable, and technologically advanced.

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References

  1. PallottiniV. SegattoM. AcconciaF. FiocchettiM. MarinoM. Mechanism underlying naringenin hypocholesterolemic effects: Involvement of estrogen receptor α subtype.Int. J. Mol. Sci.202223241580910.3390/ijms232415809 36555447
    [Google Scholar]
  2. HanX. GaoS. ChengY.N. SunY.Z. LiuW. TangL.L. RenD.M. Protective effect of naringenin-7-O-glucoside against oxidative stress induced by doxorubicin in H9c2 cardiomyocytes.Biosci. Trends201261192510.5582/bst.2012.v6.1.19 22426099
    [Google Scholar]
  3. PatelK. SinghG.K. PatelD.K. A review on pharmacological and analytical aspects of naringenin.Chin. J. Integr. Med.201824755156010.1007/s11655‑014‑1960‑x 25501296
    [Google Scholar]
  4. SehrawatN. UpadhyayS.K. SharmaA.K. KumarS. YadavM. Emerging renoprotective role of citrus flavonoid naringin: Current pharmaceutical status and future perspectives.Curr. Pharmacol. Rep.2021739610110.1007/s40495‑021‑00256‑7
    [Google Scholar]
  5. Ben-AzuB. NwokeE.E. AderibigbeA.O. OmogbiyaI.A. AjayiA.M. OlonodeE.T. UmukoroS. IwalewaE.O. Possible neuroprotective mechanisms of action involved in the neurobehavioral property of naringin in mice.Biomed. Pharmacother.201910953654610.1016/j.biopha.2018.10.055 30399589
    [Google Scholar]
  6. WangH.K. YehC.H. IwamotoT. SatsuH. ShimizuM. TotsukaM. Dietary flavonoid naringenin induces regulatory T cells via an aryl hydrocarbon receptor mediated pathway.J. Agric. Food Chem.20126092171217810.1021/jf204625y 22324845
    [Google Scholar]
  7. JinM.J. KimU. KimI.S. KimY. KimD.H. HanS.B. KimD.H. KwonO.S. YooH.H. Effects of gut microflora on pharmacokinetics of hesperidin: A study on non-antibiotic and pseudo-germ-free rats.J. Toxicol. Environ. Health A20107321-221441145010.1080/15287394.2010.511549 20954071
    [Google Scholar]
  8. DouW. ZhangJ. SunA. ZhangE. DingL. MukherjeeS. WeiX. ChouG. WangZ.T. ManiS. Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling.Br. J. Nutr.2013110459960810.1017/S0007114512005594 23506745
    [Google Scholar]
  9. BhartiS. RaniN. KrishnamurthyB. AryaD. Preclinical evidence for the pharmacological actions of naringin: A review.Planta Med.201480643745110.1055/s‑0034‑1368351 24710903
    [Google Scholar]
  10. ArafahA. RehmanM.U. MirT.M. WaliA.F. AliR. QamarW. KhanR. AhmadA. AgaS.S. AlqahtaniS. AlmatroudiN.M. Multi-therapeutic potential of naringenin (4′, 5, 7-trihydroxyflavonone): Experimental evidence and mechanisms.Plants2020912178410.3390/plants9121784 33339267
    [Google Scholar]
  11. RenugadeviJ. Milton PrabuS. Quercetin protects against oxidative stress-related renal dysfunction by cadmium in rats.Exp. Toxicol. Pathol.201062547148110.1016/j.etp.2009.06.006 19615871
    [Google Scholar]
  12. KhandavilliU.B.R. SkořepováE. SinhaA.S. BhogalaB.R. MaguireN.M. MaguireA.R. LawrenceS.E. Cocrystals and a salt of the bioactive flavonoid.Cryst. Growth Des.20181884571457710.1021/acs.cgd.8b00557
    [Google Scholar]
  13. De MarinisE. AscenziP. PellegriniM. GalluzzoP. BulzomiP. ArevaloM.A. Garcia-SeguraL.M. MarinoM. 17β-estradiol--a new modulator of neuroglobin levels in neurons: Role in neuroprotection against H2O2-induced toxicity.Neurosignals201018422323510.1159/000323906 21335947
    [Google Scholar]
  14. AhmedO.M. AbouZidS.F. AhmedN.A. ZakyM.Y. LiuH. An up-to-date review on citrus flavonoids: Chemistry and benefits in health and diseases.Curr. Pharm. Des.202127451353010.2174/18734286MTExcOTEd5 33245267
    [Google Scholar]
  15. MoradiN. FakhriS. FarzaeiM.H. AbbaszadehF. The anti-nociceptive activity of naringenin passes through L-arginine/NO/cGMP/KATP channel pathway and opioid receptors.Behav. Pharmacol.202132759059810.1097/FBP.0000000000000653 34483246
    [Google Scholar]
  16. OmarH.A. MohamedW.R. ArafaE.S.A. ShehataB.A. SherbinyG.A.E. ArabH.H. ElgendyA.N.A.M. Hesperidin alleviates cisplatin-induced hepatotoxicity in rats without inhibiting its antitumor activity.Pharmacol. Rep.201668234935610.1016/j.pharep.2015.09.007 26922538
    [Google Scholar]
  17. IoannouI. M’hiriN. ChaabanH. BoudhriouaN.M. GhoulM. Effect of the process, temperature, light and oxygen on naringin extraction and the evolution of its antioxidant activity.Int. J. Food Sci. Technol.201853122754276010.1111/ijfs.13887
    [Google Scholar]
  18. TupysA. KalembkiewiczJ. OstapiukY. MatiichukV. TymoshukO. WoźnickaE. ByczyńskiŁ. Synthesis, structural characterization and thermal studies of a novel reagent 1-[(5-benzyl-1,3-thiazol-2-yl)diazenyl]naphthalene-2-ol.J. Therm. Anal. Calorim.201712732233224210.1007/s10973‑016‑5784‑0
    [Google Scholar]
  19. ZhaoH. LiuM. LiuH. SuoR. LuC. Naringin protects endothelial cells from apoptosis and inflammation by regulating the Hippo-YAP Pathway.Biosci. Rep.2020403BSR2019343110.1042/BSR20193431 32091090
    [Google Scholar]
  20. LiaoY. WangN. NiY. XuJ. ShaoS. Electrochemical sensor based on Nbim/CNT composite for selective determination of luteolin in the flavonoids.J. Electroanal. Chem. 2015754949910.1016/j.jelechem.2015.07.014
    [Google Scholar]
  21. JoshiR. KulkarniY.A. WairkarS. Pharmacokinetic, pharmacodynamic and formulations aspects of Naringenin: An update.Life Sci.2018215435610.1016/j.lfs.2018.10.066 30391464
    [Google Scholar]
  22. Pinho-RibeiroF.A. ZarpelonA.C. FattoriV. ManchopeM.F. MizokamiS.S. CasagrandeR. VerriW.A.Jr Naringenin reduces inflammatory pain in mice.Neuropharmacology201610550851910.1016/j.neuropharm.2016.02.019 26907804
    [Google Scholar]
  23. FrydoonfarH.R. McGrathD.R. SpigelmanA.D. The variable effect on proliferation of a colon cancer cell line by the citrus fruit flavonoid Naringenin.Colorectal Dis.20035214915210.1046/j.1463‑1318.2003.00444.x 12780904
    [Google Scholar]
  24. HusainN. KumarA. Reactive oxygen species and natural antioxidants: A review.Adv. Biores.201234164175
    [Google Scholar]
  25. ur Rashid, H.; Xu, Y.; Ahmad, N.; Muhammad, Y.; Wang, L. Promising anti-inflammatory effects of chalcones via inhibition of cyclooxygenase, prostaglandin E2, inducible NO synthase and nuclear factor κb activities.Bioorg. Chem.20198733536510.1016/j.bioorg.2019.03.033 30921740
    [Google Scholar]
  26. El MohsenM.A. MarksJ. KuhnleG. Rice-EvansC. MooreK. GibsonG. DebnamE. SraiS.K. The differential tissue distribution of the citrus flavanone naringenin following gastric instillation.Free Radic. Res.200438121329134010.1080/10715760400017293 15763957
    [Google Scholar]
  27. YangY. TrevethanM. WangS. ZhaoL. Beneficial effects of citrus flavanones naringin and naringenin and their food sources on lipid metabolism: An update on bioavailability, pharmacokinetics, and mechanisms.J. Nutr. Biochem.202210410896710.1016/j.jnutbio.2022.108967 35189328
    [Google Scholar]
  28. KanazeF.I. BounartziM.I. GeorgarakisM. NiopasI. Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects.Eur. J. Clin. Nutr.200761447247710.1038/sj.ejcn.1602543 17047689
    [Google Scholar]
  29. RebelloC.J. BeylR.A. LertoraJ.J.L. GreenwayF.L. RavussinE. RibnickyD.M. PoulevA. KennedyB.J. CastroH.F. CampagnaS.R. CoulterA.A. RedmanL.M. Safety and pharmacokinetics of naringenin: A randomized, controlled, single‐ascending‐dose clinical trial.Diabetes Obes. Metab.2020221919810.1111/dom.13868 31468636
    [Google Scholar]
  30. Hernández-AquinoE. MurielP. Naringenin and the liver. In: Liver Pathophysiology: Therapies and Antioxidants.Cambridge, MassachusettsAcademic Press201710.1016/B978‑0‑12‑804274‑8.00046‑1
    [Google Scholar]
  31. 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]
  32. ChenL. DengH. CuiH. FangJ. ZuoZ. DengJ. LiY. WangX. ZhaoL. Inflammatory responses and inflammation-associated diseases in organs.Oncotarget2018967204721810.18632/oncotarget.23208 29467962
    [Google Scholar]
  33. MallahK. CouchC. BoruckiD.M. ToutonjiA. AlshareefM. TomlinsonS. Anti-inflammatory and neuroprotective agents in clinical trials for CNS disease and injury: Where do we go from here?Front. Immunol.202011202110.3389/fimmu.2020.02021 33013859
    [Google Scholar]
  34. GosslauA. LiS. HoC.T. ChenK.Y. RawsonN.E. The importance of natural product characterization in studies of their anti‐inflammatory activity.Mol. Nutr. Food Res.2011551748210.1002/mnfr.201000455 21207514
    [Google Scholar]
  35. Hernández-AquinoE. MurielP. Beneficial effects of naringenin in liver diseases: Molecular mechanisms.World J. Gastroenterol.201824161679170710.3748/wjg.v24.i16.1679 29713125
    [Google Scholar]
  36. GhoshD. KhanA.N. SinghR. BhattacharyaA. ChakravartiR. RoyS. RavichandiranV. A short review on glucogallin and its pharmacological activities.Mini Rev. Med. Chem.202222222820283010.2174/1389557522666220513150907 35570562
    [Google Scholar]
  37. ManchopeM.F. FerrazC.R. BorghiS.M. Therapeutic role of naringenin to alleviate inflammatory pain.Treatments, Mechanisms, and Adverse Reactions of Anesthetics and Analgesics.Cambridge, MassachusettsAcademic Press202210.1016/B978‑0‑12‑820237‑1.00038‑7
    [Google Scholar]
  38. MurtiY. MishraP. Synthesis, characterization, and biological evaluation of novel naringenin derivatives as anticancer agents.Curr. Bioact. Compd.202016444244810.2174/1573407215666181214114927
    [Google Scholar]
  39. MartaŻ.N. AgnieszkaW. JacekP. JeleńA. AdrianK. DagmaraS.K. Sałagacka-KubiakA. BalcerczakE. NFKB2 gene expression in patients with peptic ulcer diseases and gastric cancer.Mol. Biol. Rep.20204732015202110.1007/s11033‑020‑05299‑5 32056043
    [Google Scholar]
  40. ChinL.H. HonC.M. ChellappanD.K. ChellianJ. MadheswaranT. ZeeshanF. AwasthiR. AljabaliA.A.A. TambuwalaM.M. DurejaH. NegiP. KapoorD.N. GoyalR. PaudelK.R. SatijaS. GuptaG. HsuA. WarkP. MehtaM. WadhwaR. HansbroP.M. DuaK. Molecular mechanisms of action of naringenin in chronic airway diseases.Eur. J. Pharmacol.202087917313910.1016/j.ejphar.2020.173139 32343971
    [Google Scholar]
  41. YuD. MaC. YueZ. YaoX. MaoC. Protective effect of naringenin against lipopolysaccharide-induced injury in normal human bronchial epithelium via suppression of MAPK signaling.Inflammation201538119520410.1007/s10753‑014‑0022‑z 25303878
    [Google Scholar]
  42. EanesL. PatelY.M. Inhibition of the MAPK pathway alone is insufficient to account for all of the cytotoxic effects of naringenin in MCF-7 breast cancer cells.Biochim. Open20163647110.1016/j.biopen.2016.09.004 29450133
    [Google Scholar]
  43. ChenY. NieY. LuoY. LinF. ZhengY. ChengG. WuH. ZhangK. SuW. ShenJ. LiP. Protective effects of naringin against paraquat-induced acute lung injury and pulmonary fibrosis in mice.Food Chem. Toxicol.20135813314010.1016/j.fct.2013.04.024 23603004
    [Google Scholar]
  44. ShiraniK. YousefsaniB.S. ShiraniM. KarimiG. Protective effects of naringin against drugs and chemical toxins induced hepatotoxicity: A review.Phytother. Res.20203481734174410.1002/ptr.6641 32067280
    [Google Scholar]
  45. GoldwasserJ. CohenP.Y. LinW. KitsbergD. BalaguerP. PolyakS.J. ChungR.T. YarmushM.L. NahmiasY. Naringenin inhibits the assembly and long-term production of infectious hepatitis C virus particles through a PPAR-mediated mechanism.J. Hepatol.201155596397110.1016/j.jhep.2011.02.011 21354229
    [Google Scholar]
  46. MicaroniM. StanleyA.C. KhromykhT. VenturatoJ. WongC.X.F. LimJ.P. MarshB.J. StorrieB. GleesonP.A. StowJ.L. Rab6a/a′ are important Golgi regulators of pro-inflammatory TNF secretion in macrophages.PLoS One201382e5703410.1371/journal.pone.0057034 23437303
    [Google Scholar]
  47. HuangJ. BrameshuberM. ZengX. XieJ. LiQ. ChienY. ValituttiS. DavisM.M. A single peptide-major histocompatibility complex ligand triggers digital cytokine secretion in CD4(+) T cells.Immunity201339584685710.1016/j.immuni.2013.08.036 24120362
    [Google Scholar]
  48. LinC.F. KuoY.T. ChenT.Y. ChienC.T. Quercetin-rich guava (Psidium guajava) juice in combination with trehalose reduces autophagy, apoptosis and pyroptosis formation in the kidney and pancreas of type II diabetic rats.Molecules201621333410.3390/molecules21030334 26978332
    [Google Scholar]
  49. ZobeiriM. BelwalT. ParviziF. NaseriR. FarzaeiM.H. NabaviS.F. SuredaA. NabaviS.M. Naringenin and its nano-formulations for fatty liver: Cellular modes of action and clinical perspective.Curr. Pharm. Biotechnol.201819319620510.2174/1389201019666180514170122 29766801
    [Google Scholar]
  50. JinL. ZengW. ZhangF. ZhangC. LiangW. Naringenin ameliorates acute inflammation by regulating intracellular cytokine degradation.J. Immunol.2017199103466347710.4049/jimmunol.1602016 28993518
    [Google Scholar]
  51. GuptaS.C. TyagiA.K. Deshmukh-TaskarP. HinojosaM. PrasadS. AggarwalB.B. Downregulation of tumor necrosis factor and other proinflammatory biomarkers by polyphenols.Arch. Biochem. Biophys.2014559919910.1016/j.abb.2014.06.006 24946050
    [Google Scholar]
  52. Louw-du ToitR. HapgoodJ.P. AfricanderD. Medroxyprogesterone acetate differentially regulates interleukin (IL)-12 and IL-10 in a human ectocervical epithelial cell line in a glucocorticoid receptor (GR)-dependent manner.J. Biol. Chem.201428945311363114910.1074/jbc.M114.587311 25202013
    [Google Scholar]
  53. KauppinenA. SuuronenT. OjalaJ. KaarnirantaK. SalminenA. Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders.Cell. Signal.201325101939194810.1016/j.cellsig.2013.06.007 23770291
    [Google Scholar]
  54. VezzaT. Rodríguez-NogalesA. AlgieriF. UtrillaM.P. Rodriguez-CabezasM.E. GalvezJ. Flavonoids in inflammatory bowel disease: A review.Nutrients201684211
    [Google Scholar]
  55. HämäläinenM. NieminenR. VuorelaP. HeinonenM. MoilanenE. Anti-inflammatory effects of flavonoids: Genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages.Mediators Inflamm.200720074567310.1155/2007/45673 18274639
    [Google Scholar]
  56. Roman-BlasJ.A. JimenezS.A. NF-κB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis.Osteoarthritis Cartilage200614983984810.1016/j.joca.2006.04.008 16730463
    [Google Scholar]
  57. YamamotoY. GaynorR.B. IκB kinases: Key regulators of the NF-κB pathway.Trends Biochem. Sci.2004292727910.1016/j.tibs.2003.12.003 15102433
    [Google Scholar]
  58. ChenS. DingY. TaoW. ZhangW. LiangT. LiuC. Naringenin inhibits TNF-α induced VSMC proliferation and migration via induction of HO-1.Food Chem. Toxicol.20125093025303110.1016/j.fct.2012.06.006 22709785
    [Google Scholar]
  59. StabrauskieneJ. KopustinskieneD.M. LazauskasR. BernatonieneJ. Naringin and naringenin: Their mechanisms of action and the potential anticancer activities.Biomedicines2022107168610.3390/biomedicines10071686 35884991
    [Google Scholar]
  60. WadhwaR. PaudelK.R. ChinL.H. HonC.M. MadheswaranT. GuptaG. PanneerselvamJ. LakshmiT. SinghS.K. GulatiM. DurejaH. Anti‐inflammatory and anticancer activities of Naringenin‐loaded liquid crystalline nanoparticles in vitro.J. Food Biochem.2020451e1357210.1111/jfbc.13572
    [Google Scholar]
  61. OjewoleJ.A.O. Antinociceptive, anti-inflammatory and antidiabetic properties of Hypoxis hemerocallidea Fisch. & C.A. Mey. (Hypoxidaceae) corm [‘African Potato’] aqueous extract in mice and rats.J. Ethnopharmacol.2006103112613410.1016/j.jep.2005.07.012 16191469
    [Google Scholar]
  62. DongB. ZhouY. WangW. ScottJ. KimK. SunZ. GuoQ. LuY. GonzalesN.M. WuH. HartigS.M. YorkR.B. YangF. MooreD.D. Vitamin D receptor activation in liver macrophages ameliorates hepatic inflammation, steatosis, and insulin resistance in mice.Hepatology20207151559157410.1002/hep.30937 31506976
    [Google Scholar]
  63. RexJ. LutzA. FalettiL.E. AlbrechtU. ThomasM. BodeJ.G. BornerC. SawodnyO. MerfortI. IL-1β and TNFα differentially influence NF-κB activity and FasL-induced apoptosis in primary murine hepatocytes during LPS-induced inflammation.Front. Physiol.20191011710.3389/fphys.2019.00117 30842741
    [Google Scholar]
  64. LinH.J. KuK.L. LinI.H. YehC.C. Naringenin attenuates hepatitis B virus X protein-induced hepatic steatosis.BMC Complement. Altern. Med.201717150510.1186/s12906‑017‑2019‑2 29183361
    [Google Scholar]
  65. AssiniJ.M. MulvihillE.E. BurkeA.C. SutherlandB.G. TelfordD.E. ChhokerS.S. SawyezC.G. DrangovaM. AdamsA.C. KharitonenkovA. PinC.L. HuffM.W. Naringenin prevents obesity, hepatic steatosis, and glucose intolerance in male mice independent of fibroblast growth factor 21.Endocrinology201515662087210210.1210/en.2014‑2003 25774553
    [Google Scholar]
  66. MoosavianS.A. SathyapalanT. JamialahmadiT. SahebkarA. The emerging role of nanomedicine in the management of nonalcoholic fatty liver disease: A state-of-the-art review.Bioinorg. Chem. Appl.20212021404141510.1155/2021/4041415
    [Google Scholar]
  67. Hernández-AquinoE. ZarcoN. Casas-GrajalesS. Ramos-TovarE. Flores-BeltránR.E. ArauzJ. ShibayamaM. FavariL. TsutsumiV. SegoviaJ. MurielP. Naringenin prevents experimental liver fibrosis by blocking TGFβ-Smad3 and JNK-Smad3 pathways.World J. Gastroenterol.201723244354436810.3748/wjg.v23.i24.4354 28706418
    [Google Scholar]
  68. WaliA.F. RashidS. RashidS.M. AnsariM.A. KhanM.R. HaqN. AlharethD.Y. AhmadA. RehmanM.U. Naringenin regulates doxorubicin-induced liver dysfunction: Impact on oxidative stress and inflammation.Plants20209455010.3390/plants9040550 32344607
    [Google Scholar]
  69. UrataY. OsugaY. IzumiG. TakamuraM. KogaK. NagaiM. HaradaM. HirataT. HirotaY. YoshinoO. TaketaniY. Interleukin-1β stimulates the secretion of thymic stromal lymphopoietin (TSLP) from endometrioma stromal cells: Possible involvement of TSLP in endometriosis.Hum. Reprod.201227103028303510.1093/humrep/des291 22888172
    [Google Scholar]
  70. DysonM.T. BulunS.E. Cutting SRC-1 down to size in endometriosis.Nat. Med.20121871016101810.1038/nm.2855 22772552
    [Google Scholar]
  71. BartiromoL. SchimberniM. VillanacciR. OttolinaJ. DolciC. SalmeriN. ViganòP. CandianiM. Endometriosis and Phytoestrogens: Friends or Foes? A Systematic Review.Nutrients2021138253210.3390/nu13082532 34444692
    [Google Scholar]
  72. PellegriniM. BulzomiP. GalluzzoP. LecisM. LeoneS. PallottiniV. MarinoM. Naringenin modulates skeletal muscle differentiation via estrogen receptor α and β signal pathway regulation.Genes Nutr.20149542510.1007/s12263‑014‑0425‑3 25156241
    [Google Scholar]
  73. SalehiB. FokouP. Sharifi-RadM. ZuccaP. PezzaniR. MartinsN. Sharifi-RadJ. The therapeutic potential of naringenin: A review of clinical trials.Pharmaceuticals20191211110.3390/ph12010011 30634637
    [Google Scholar]
  74. ParkS. LimW. BazerF.W. SongG. Naringenin induces mitochondria-mediated apoptosis and endoplasmic reticulum stress by regulating MAPK and AKT signal transduction pathways in endometriosis cells.Mol. Hum. Reprod.2017231284285410.1093/molehr/gax057 29121349
    [Google Scholar]
  75. LiR. ZhangY. RasoolS. GeethaT. BabuJ.R. Effects and underlying mechanisms of bioactive compounds on type 2 diabetes mellitus and Alzheimer’s disease.Oxid. Med. Cell. Longev.2019201912510.1155/2019/8165707 30800211
    [Google Scholar]
  76. MukhtarM.H. El-EmshatyH.M. AlamodiH.S. NasifW.A. The activity of serum 8-iso-prostaglandin F2α as oxidative stress marker in patients with diabetes mellitus type 2 and associated dyslipidemic hyperglycemia.J. Diabetes Mellitus20166431833210.4236/jdm.2016.64033
    [Google Scholar]
  77. ZaidunN.H. ThentZ.C. LatiffA.A. Combating oxidative stress disorders with citrus flavonoid.Naringenin. Life Sci.201820811112210.1016/j.lfs.2018.07.017 30021118
    [Google Scholar]
  78. TsaiS.J. HuangC.S. MongM.C. KamW.Y. HuangH.Y. YinM.C. Anti-inflammatory and antifibrotic effects of naringenin in diabetic mice.J. Agric. Food Chem.201260151452110.1021/jf203259h 22117528
    [Google Scholar]
  79. PriscillaD.H. RoyD. SureshA. KumarV. ThirumuruganK. Naringenin inhibits α-glucosidase activity: A promising strategy for the regulation of postprandial hyperglycemia in high fat diet fed streptozotocin induced diabetic rats.Chem. Biol. Interact.2014210778510.1016/j.cbi.2013.12.014 24412302
    [Google Scholar]
  80. BhattacharyaS. OksbjergN. YoungJ.F. JeppesenP.B. Caffeic acid, naringenin and quercetin enhance glucose‐stimulated insulin secretion and glucose sensitivity in INS‐1E cells.Diabetes Obes. Metab.201416760261210.1111/dom.12236 24205999
    [Google Scholar]
  81. SharmaA. PatarA.K. BhanS. Cytoprotective, antihyperglycemic and antioxidative effect of naringenin on liver and kidneys of Swiss diabetic mice.Int. J. Health Sci. Res.20166118131
    [Google Scholar]
  82. ChenR. QiQ.L. WangM.T. LiQ.Y. Therapeutic potential of naringin: An overview.Pharm. Biol.201654123203321010.1080/13880209.2016.1216131 27564838
    [Google Scholar]
  83. SirovinaD. OršolićN. GregorovićG. KončićM.Z. Naringenin ameliorates pathological changes in liver and kidney of diabetic mice: A preliminary study/Naringenin reducira histopatološke promjene u jetri i bubregu miševa s dijabetesom.Arh. Hig. Rada Toksikol.2016671192410.1515/aiht‑2016‑67‑2708 27092635
    [Google Scholar]
  84. SchirbelA. ReichertA. RollS. BaumgartD.C. BüningC. WittigB. WiedenmannB. DignassA. SturmA. Impact of pain on health-related quality of life in patients with inflammatory bowel disease.World J. Gastroenterol.201016253168317710.3748/wjg.v16.i25.3168 20593502
    [Google Scholar]
  85. SartorR.B. Review article: The potential mechanisms of action of rifaximin in the management of inflammatory bowel diseases.Aliment. Pharmacol. Ther.201643S1Suppl. 1273610.1111/apt.13436 26618923
    [Google Scholar]
  86. StroberW. FussI.J. Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases.Gastroenterology2011140617561767.e110.1053/j.gastro.2011.02.016 21530742
    [Google Scholar]
  87. CaoH. LiuJ. ShenP. CaiJ. HanY. ZhuK. FuY. ZhangN. ZhangZ. CaoY. Protective effect of naringin on DSS-induced ulcerative colitis in mice.J. Agric. Food Chem.20186650131331314010.1021/acs.jafc.8b03942 30472831
    [Google Scholar]
  88. KimT. PaudelK.R. KimD.W. Eriobotrya japonica leaf extract attenuates airway inflammation in ovalbumin-induced mice model of asthma.J. Ethnopharmacol.202025311208210.1016/j.jep.2019.112082 31310829
    [Google Scholar]
  89. MehtaM. Deeksha; Sharma, N.; Vyas, M.; Khurana, N.; Maurya, P.K.; Singh, H.; Andreoli de Jesus, T.P.; Dureja, H.; Chellappan, D.K.; Gupta, G.; Wadhwa, R.; Collet, T.; Hansbro, P.M.; Dua, K.; Satija, S. Interactions with the macrophages: An emerging targeted approach using novel drug delivery systems in respiratory diseases.Chem. Biol. Interact.2019304101910.1016/j.cbi.2019.02.021 30849336
    [Google Scholar]
  90. da CunhaA.A. NuñezN.K. de SouzaR.G. Moraes VargasM.H. SilveiraJ.S. AntunesG.L. DuranteL.S. PortoB.N. MarczakE.S. JonesM.H. PitrezP.M. Recombinant human deoxyribonuclease therapy improves airway resistance and reduces DNA extracellular traps in a murine acute asthma model.Exp. Lung Res.2016422667410.3109/01902148.2016.1143537 27070484
    [Google Scholar]
  91. AlbercaR.W. TeixeiraF.M.E. BeserraD.R. de OliveiraE.A. AndradeM.M.S. PietrobonA.J. SatoM.N. Perspective: The potential effects of naringenin in COVID-19.Front. Immunol.20201157091910.3389/fimmu.2020.570919 33101291
    [Google Scholar]
  92. ZengL. SunS. ChenP. YeQ. LinX. WanH. CaiY. ChenX. Mechanism of Peitu Shengjin formula shenlingbaizhu powder in treating bronchial asthma and allergic colitis through different diseases with simultaneous treatment based on network pharmacology and molecular docking.Evid. Based Complement. Alternat. Med.2022202212310.1155/2022/4687788 35586697
    [Google Scholar]
  93. IwamuraC. ShinodaK. YoshimuraM. WatanabeY. ObataA. NakayamaT. Naringenin chalcone suppresses allergic asthma by inhibiting the type-2 function of CD4 T cells.Allergol. Int.2010591677310.2332/allergolint.09‑OA‑0118 20035147
    [Google Scholar]
  94. ShiR. XiaoZ.T. ZhengY.J. ZhangY.L. XuJ.W. HuangJ.H. ZhouW.L. LiP.B. SuW.W. Naringenin regulates CFTR activation and expression in airway epithelial cells.Cell. Physiol. Biochem.20174431146116010.1159/000485419 29179179
    [Google Scholar]
  95. KroemerG. PouyssegurJ. Tumor cell metabolism: Cancer’s Achilles’ heel.Cancer Cell200813647248210.1016/j.ccr.2008.05.005 18538731
    [Google Scholar]
  96. Ghanbari-MovahedM. JacksonG. FarzaeiM.H. BishayeeA. A systematic review of the preventive and therapeutic effects of naringin against human malignancies.Front. Pharmacol.20211263984010.3389/fphar.2021.639840 33854437
    [Google Scholar]
  97. GinwalaR. BhavsarR. ChigbuD.I. JainP. KhanZ.K. Potential role of flavonoids in treating chronic inflammatory diseases with a special focus on the anti-inflammatory activity of apigenin.Antioxidants2019823510.3390/antiox8020035 30764536
    [Google Scholar]
  98. TodoricJ. AntonucciL. KarinM. Targeting inflammation in cancer prevention and therapy.Cancer Prev. Res. (Phila.)201691289590510.1158/1940‑6207.CAPR‑16‑0209 27913448
    [Google Scholar]
  99. ZhangH.W. HuJ.J. FuR.Q. LiuX. ZhangY.H. LiJ. LiuL. LiY.N. DengQ. LuoQ.S. OuyangQ. GaoN. Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells.Sci. Rep.2018811125510.1038/s41598‑018‑29308‑7 30050147
    [Google Scholar]
  100. WadhwaR. PaudelK.R. ChinL.H. HonC.M. MadheswaranT. GuptaG. PanneerselvamJ. LakshmiT. SinghS.K. GulatiM. DurejaH. HsuA. MehtaM. AnandK. DevkotaH.P. ChellianJ. ChellappanD.K. HansbroP.M. DuaK. Anti‐inflammatory and anticancer activities of Naringenin‐loaded liquid crystalline nanoparticles in vitro.J. Food Biochem.2021451e1357210.1111/jfbc.13572 33249629
    [Google Scholar]
  101. ChangH.L. ChangY.M. LaiS.C. ChenK.M. WangK.C. ChiuT.T. ChangF.H. HsuL.S. Naringenin inhibits migration of lung cancer cells via the inhibition of matrix metalloproteinases-2 and −9.Exp. Ther. Med.201713273974410.3892/etm.2016.3994 28352360
    [Google Scholar]
  102. 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]
  103. GanapathyE. RajasekaranD. SivalingamM. ShukkurM.F. ShukkurE.A. DhanapalS. Naringenin Inhibits Oxidative Stress Induced Macromolecular Damage in N-methyl N-nitro N-nitrosoguanidine Induced Gastric Carcinogenesis in Wistar Rats.Gastric Carcinoma-New Insights into Current Management; InTechOpen: London, 201311110.5772/52260
    [Google Scholar]
  104. 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]
  105. 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]
  106. LinE.J. ZhangX. WangD.Y. HongS.Z. LiL.Y. Naringenin modulates the metastasis of human prostate cancer cells by down regulating the matrix metalloproteinases -2/-9 via ROS/ERK1/2 pathways.Bangladesh J. Pharmacol.20149341942710.3329/bjp.v9i3.19730
    [Google Scholar]
  107. LiuP. BianY. FanY. ZhongJ. LiuZ. Protective effect of naringin on in vitro gut-vascular barrier disruption of intestinal microvascular endothelial cells induced by TNF-α.J. Agric. Food Chem.202068116817510.1021/acs.jafc.9b06347 31850758
    [Google Scholar]
  108. GreenbergA.S. ReevesA.R. The good and bad of adipose tissue macrophage exosomes in obesity.Cell Metab.202133470070210.1016/j.cmet.2021.03.011 33826911
    [Google Scholar]
  109. LolmèdeK. DuffautC. Zakaroff-GirardA. BouloumiéA. Immune cells in adipose tissue: Key players in metabolic disorders.Diabetes Metab.201137428329010.1016/j.diabet.2011.03.002 21507694
    [Google Scholar]
  110. SurmiB.K. WebbC.D. RistauA.C. HastyA.H. Absence of macrophage inflammatory protein-1α does not impact macrophage accumulation in adipose tissue of diet-induced obese mice.Am. J. Physiol. Endocrinol. Metab.20102993E437E44510.1152/ajpendo.00050.2010 20551286
    [Google Scholar]
  111. LeeM.S. ShinY. JungS. KimS.Y. JoY.H. KimC.T. YunM.K. LeeS.J. SohnJ. YuH.J. KimY. The inhibitory effect of tartary buckwheat extracts on adipogenesis and inflammatory response.Molecules2017227116010.3390/molecules22071160 28704952
    [Google Scholar]
  112. WangQ. OuY. HuG. WenC. YueS. ChenC. XuL. XieJ. DaiH. XiaoH. ZhangY. QiR. Naringenin attenuates non‐ alcoholic fatty liver disease by down‐regulating the NLRP3/NF‐κB pathway in mice.Br. J. Pharmacol.202017781806182110.1111/bph.14938 31758699
    [Google Scholar]
  113. MuH. ZhouQ. YangR. ZengJ. LiX. ZhangR. TangW. LiH. WangS. ShenT. HuangX. DouL. DongJ. Naringin attenuates high fat diet induced non-alcoholic fatty liver disease and gut bacterial dysbiosis in mice.Front. Microbiol.20201158506610.3389/fmicb.2020.585066 33281780
    [Google Scholar]
  114. KapoorR. SirohiV.K. GuptaK. DwivediA. Naringenin ameliorates of endometriosis by modulating Nrf2/Keap1/HO1 axis and inducing apoptosis in rats.J. Nutr. Biochem.20197021522610.1016/j.jnutbio.2019.05.003 31252288
    [Google Scholar]
  115. SyedA.A. RezaM.I. ShafiqM. KumariyaS. SinghP. HusainA. HanifK. GayenJ.R. Naringin ameliorates type 2 diabetes mellitus-induced steatohepatitis by inhibiting RAGE/NF-κB mediated mitochondrial apoptosis.Life Sci.202025711811810.1016/j.lfs.2020.118118 32702445
    [Google Scholar]
  116. RajappaR. SireeshD. SalaiM.B. RamkumarK.M. Sarvajayakesavulu, S.; Madhunapantula, S.V. Treatment with naringenin elevates the activity of transcription factor Nrf2 to protect pancre- atic β-cells from streptozotocin-induced diabetes in vitro and in vivo.Front. Pharmacol.20199156210.3389/fphar.2018.01562 30745874
    [Google Scholar]
  117. ChoiJ. LeeD.H. JangH. ParkS.Y. SeolJ.W. Naringenin exerts anticancer effects by inducing tumor cell death and inhibiting angiogenesis in malignant melanoma.Int. J. Med. Sci.202017183049305710.7150/ijms.44804 33173425
    [Google Scholar]
  118. ZhouJ. XiaL. ZhangY. Naringin inhibits thyroid cancer cell proliferation and induces cell apoptosis through repressing PI3K/AKT pathway.Pathol. Res. Pract.20192151215270710.1016/j.prp.2019.152707 31727500
    [Google Scholar]
  119. ZhaoZ. JinG. GeY. GuoZ. Naringenin inhibits migration of breast cancer cells via inflammatory and apoptosis cell signaling pathways.Inflammopharmacol2018271021103610.1007/s10787‑018‑00556‑3
    [Google Scholar]
  120. Tsuhako, R.; Yoshida, H.; Sugita, C.; Kurokawa, M. Naringenin suppresses neutrophil infiltration into adipose tissue in high-fat diet- induced obese mice.J. Nat. Med.202074122923710.1007/s11418‑019‑01332‑5 31218550
    [Google Scholar]
  121. JasemiS.V. KhazaeiH. FakhriS. Mohammadi-NooriE. FarzaeiM.H. Naringenin improves ovalbumin‐Induced allergic asthma in rats through antioxidant and anti‐inflammatory effects.Evid. Based Complementary. Altern. Med.202220221911079810.1155/2022/9110798
    [Google Scholar]
  122. TsuhakoR. YoshidaH. SugitaC. KurokawaM. Naringenin suppresses neutrophil infiltration into adipose tissue in high-fat diet-induced obese mice.J. Nat. Med.202074122923710.1007/s11418‑019‑01332‑5 31218550
    [Google Scholar]
  123. JiaoH. SuW. LiP. LiaoY. ZhouQ. ZhuN. HeL. Therapeutic effects of naringin in a guinea pig model of ovalbumin-induced cough-variant asthma.Pulm. Pharmacol. Ther.201533596510.1016/j.pupt.2015.07.002 26169899
    [Google Scholar]
  124. GandhiG.R. NetaM.T.S.L. SathiyabamaR.G. QuintansJ.S.S. de Oliveira e Silva, A.M.; Araújo, A.A.S.; Narain, N.; Júnior, L.J.Q.; Gurgel, R.Q. Flavonoids as Th1/Th2 cytokines immunomodulators: A systematic review of studies on animal models.Phytomedicine201844748410.1016/j.phymed.2018.03.057 29895495
    [Google Scholar]
  125. NiuX. WuC. LiM. ZhaoQ. MeydaniS.N. WangJ. WuD. Naringenin is an inhibitor of T cell effector functions.J. Nutr. Biochem.201858717910.1016/j.jnutbio.2018.04.008 29885599
    [Google Scholar]
  126. PonzoV. GoitreI. FaddaM. GambinoR. De FrancescoA. SoldatiL. GentileL. MagistroniP. CassaderM. BoS. Dietary flavonoid intake and cardiovascular risk: A population-based cohort study.J. Transl. Med.201513121810.1186/s12967‑015‑0573‑2 26152229
    [Google Scholar]
  127. KiranS.D. RohiniP. BhagyasreeP. Flavonoid: A review on Naringenin.J. Pharmacogn. Phytochem.20176527782783
    [Google Scholar]
  128. AgrawalA.D. Pharmacological activities of flavonoids: A review.Int. J. Pharm. Sci. Nanotechnol.20114213941398
    [Google Scholar]
  129. AlamF. MohammadinK. ShafiqueZ. AmjadS.T. AsadM.H.H. Citrus flavonoids as potential therapeutic agents: A review.Phytother. Res.20223641417144110.1002/ptr.7261 34626134
    [Google Scholar]
  130. DuntasL.H. Resveratrol and its impact on aging and thyroid function.J. Endocrinol. Invest.20113410788792 21946130
    [Google Scholar]
  131. MilerM. ŽivanovićJ. AjdžanovićV. MilenkovicD. JarićI. Šošić-JurjevićB. MiloševićV. Citrus flavanones upregulate thyrotroph Sirt1 and differently affect thyroid Nrf2 expressions in old-aged Wistar rats.J. Agric. Food Chem.202068318242825410.1021/acs.jafc.0c03079 32657124
    [Google Scholar]
  132. CalabreseV. CorneliusC. Dinkova-KostovaA.T. CalabreseE.J. MattsonM.P. Cellular stress responses, the hormesis paradigm, and vitagenes: Novel targets for therapeutic intervention in neurodegenerative disorders.Antioxid. Redox Signal.201013111763181110.1089/ars.2009.3074 20446769
    [Google Scholar]
  133. HwangJ. YaoH. CaitoS. SundarI.K. RahmanI. Redox regulation of SIRT1 in inflammation and cellular senescence.Free Radic. Biol. Med.20136119511010.1016/j.freeradbiomed.2013.03.015 23542362
    [Google Scholar]
  134. ZirosP.G. HabeosI.G. ChartoumpekisD.V. NtalampyraE. SommE. RenaudC.O. BongiovanniM. TrougakosI.P. YamamotoM. KenslerT.W. SantistebanP. CarrascoN. Ris-StalpersC. AmendolaE. LiaoX.H. RossichL. ThomaszL. JuvenalG.J. RefetoffS. SykiotisG.P. NFE2-related transcription factor 2 coordinates antioxidant defense with thyroglobulin production and iodination in the thyroid gland.Thyroid201828678079810.1089/thy.2018.0018 29742982
    [Google Scholar]
  135. Di DalmaziG. GiulianiC. Plant constituents and thyroid: A revision of the main phytochemicals that interfere with thyroid function.Food Chem. Toxicol.202115211215810.1016/j.fct.2021.112158 33789121
    [Google Scholar]
  136. GlatignyS. BettelliE. Experimental autoimmune encephalomyelitis (EAE) as animal models of multiple sclerosis (MS).Cold Spring Harb. Perspect. Med.2018811a02897710.1101/cshperspect.a028977 29311122
    [Google Scholar]
  137. CostaB.K. PassosG.R. BeckerJ. SatoD.K. MOG-IgG associated optic neuritis is not multiple sclerosis.Arq. Neuropsiquiatr.2017751068769110.1590/0004‑282x20170121 29166458
    [Google Scholar]
  138. TeixeiraN.B. PicoloG. GiardiniA.C. BoumezbeurF. PottierG. KuhnastB. ServentD. BenoitE. Alterations of peripheral nerve excitability in an experimental autoimmune encephalomyelitis mouse model for multiple sclerosis.J. Neuroinflammation202017126610.1186/s12974‑020‑01936‑9 32894170
    [Google Scholar]
  139. XiangY.J. RenM. JiangH. YangT.T. HeY. AoD.H. WangY.Y. ZhangQ. HeX.J. GaoX.G. LiuG.Z. Ex vivoexpansion of antigen-specific CD4+CD25+ regulatory T cells from autologous naïve CD4+ T cells of multiple sclerosis patients as a potential therapeutic approach.Eur. Rev. Med. Pharmacol. Sci.2016202452615270 28051239
    [Google Scholar]
  140. LiddelowS. HoyerD. Astrocytes: Adhesion molecules and immunomodulation.Curr. Drug Targets201617161871188110.2174/1389450117666160101120703 26721411
    [Google Scholar]
  141. WangJ. QiY. NiuX. TangH. MeydaniS.N. WuD. Dietary naringenin supplementation attenuates experimental autoimmune encephalomyelitis by modulating autoimmune inflammatory responses in mice.J. Nutr. Biochem.20185413013910.1016/j.jnutbio.2017.12.004 29331869
    [Google Scholar]
  142. ChehadeL. JaafarZ.A. El MasriD. ZmerlyH. KreidiehD. TannirH. ItaniL. El GhochM. Lifestyle modification in rheumatoid arthritis: Dietary and physical activity recommendations based on evidence.Curr. Rheumatol. Rev.201915320921410.2174/1573397115666190121135940 30666911
    [Google Scholar]
  143. SimaderE. PuchnerA. SaferdingV. P122 Important role of dendritic cells in inflammatory arthritis.Ann. Rheum. Dis.201978A54A55
    [Google Scholar]
  144. HaslamC. JettenJ. CruwysT. DingleG.A. HaslamS.A. The new psychology of health: Unlocking the social cure.London, United KingdomRoutledge201851010.4324/9781315648569
    [Google Scholar]
  145. NiuX. SangH. WangJ. Naringenin attenuates experimental autoimmune encephalomyelitis by protecting the intact of blood-brain barrier and controlling inflammatory cell migration.J. Nutr. Biochem.20218910856010.1016/j.jnutbio.2020.108560 33249188
    [Google Scholar]
  146. PandaS. KarA. Antithyroid effects of naringin, hesperidin and rutin in l-T4 induced hyperthyroid rats: Possible mediation through 5′DI activity.Pharmacol. Rep.20146661092109910.1016/j.pharep.2014.07.002 25443740
    [Google Scholar]
  147. ManchopeM.F. ArteroN.A. FattoriV. MizokamiS.S. PitolD.L. IssaJ.P.M. FukadaS.Y. CunhaT.M. Alves-FilhoJ.C. CunhaF.Q. CasagrandeR. VerriW.A., Jr Naringenin mitigates titanium dioxide (TiO2)-induced chronic arthritis in mice: Role of oxidative stress, cytokines, and NFκBInflamm. Res.20186711-12997101210.1007/s00011‑018‑1195‑y30370484
    [Google Scholar]
  148. ZhangG. SunG. GuanH. LiM. LiuY. TianB. HeZ. FuQ. Naringenin nanocrystals for improving anti rheumatoid arthritis activity.Asian J Pharm Sci202116681682510.1016/j.ajps.2021.09.001Hajizadeh, A.
    [Google Scholar]
  149. HajizadehA. Abtahi FroushaniS.M. TehraniA.A. AziziS. Bani HashemiS.R. Effects of naringenin on experimentally in- duced rheumatoid arthritis in wistar rats.Arch. Razi Inst.2021764903912 35096326
    [Google Scholar]
  150. JasemiS.V. KhazaeiH. FakhriS. Mohammadi-NooriE. Farzaei, M.H. Naringenin improves ovalbumin-induced allergic asthma in rats through antioxidant and anti-inflammatory effects.Evid. Based Complement. Alternat. Med.2022202211010.1155/2022/9110798 35419072
    [Google Scholar]
  151. HajizadehA. Abtahi FroushaniS.M. TehraniA.A. AziziS. Bani HashemiS.R. Effects of naringenin on experimentally induced rheumatoid arthritis in wistar rats.Arch. Razi Inst.2021764903912 35096326
    [Google Scholar]
  152. JasemiS.V. KhazaeiH. FakhriS. Mohammadi-NooriE. FarzaeiM.H. Naringenin improves ovalbumin-induced allergic asthma in rats through antioxidant and anti-inflammatory effects.Evid. Based Complement. Alternat. Med.2022202211010.1155/2022/9110798 35419072
    [Google Scholar]
  153. NahJ. YuanJ. JungY.K. Autophagy in neurodegenerative diseases: From mechanism to therapeutic approach.Mol. Cells201538538138910.14348/molcells.2015.0034 25896254
    [Google Scholar]
  154. WalP. DwivediJ. WalA. VigH. SinghY. Detailed insight into the pathophysiology and the behavioral complications associated with the Parkinson’s disease and its medications.Future J Pharmaceut Sci2022813310.1186/s43094‑022‑00425‑5
    [Google Scholar]
  155. GuoF. LiuX. CaiH. LeW. Autophagy in neurodegenerative diseases: Pathogenesis and therapy.Brain Pathol.201828131310.1111/bpa.12545 28703923
    [Google Scholar]
  156. ValléeA. LecarpentierY. GuillevinR. ValléeJ.N. Effects of cannabidiol interactions with Wnt/β-catenin pathway and PPARγ on oxidative stress and neuroinflammation in Alzheimer’s disease.Acta Biochim. Biophys. Sin. 2017491085386610.1093/abbs/gmx073 28981597
    [Google Scholar]
  157. TangY. LeW. Differential roles of M1 and M2 microglia in neurodegenerative diseases.Mol. Neurobiol.20165321181119410.1007/s12035‑014‑9070‑5 25598354
    [Google Scholar]
  158. TalebiM. TalebiM. SamarghandianS. Association of Crocus sativus with cognitive dysfunctions and Alzheimer’s disease: A systematic review.Biointerface Res. Appl. Chem.202111174687492
    [Google Scholar]
  159. HuX. LeakR.K. ShiY. SuenagaJ. GaoY. ZhengP. ChenJ. Microglial and macrophage polarization-new prospects for brain repair.Nat. Rev. Neurol.2015111566410.1038/nrneurol.2014.207 25385337
    [Google Scholar]
  160. ZhangB. WeiY.Z. WangG.Q. LiD.D. ShiJ.S. ZhangF. Targeting MAPK pathways by naringenin modulates microglia M1/M2 polarization in lipopolysaccharide-stimulated cultures.Front. Cell. Neurosci.20191253110.3389/fncel.2018.00531 30687017
    [Google Scholar]
  161. SpagnuoloC. MocciaS. RussoG.L. Anti-inflammatory effects of flavonoids in neurodegenerative disorders.Eur. J. Med. Chem.201815310511510.1016/j.ejmech.2017.09.001 28923363
    [Google Scholar]
  162. AlifarsangiA. Esmaeili-MahaniS. SheibaniV. AbbasnejadM. The citrus flavanone naringenin prevents the development of morphine analgesic tolerance and conditioned place preference in male rats.Am. J. Drug Alcohol Abuse2021471435110.1080/00952990.2020.1813296 33006902
    [Google Scholar]
  163. LabrieV. BrundinP. Alpha-synuclein to the rescue: Immune cell recruitment by alpha-synuclein during gastrointestinal infection.J. Innate Immun.20179543744010.1159/000479653 28866688
    [Google Scholar]
  164. JayarajR.L. BeiramR. AzimullahS. MeeranM.F.N. OjhaS.K. AdemA. JalalF.Y. Lycopodium attenuates loss of dopaminergic neurons by suppressing oxidative stress and neuroinflammation in a rat model of Parkinson’s disease.Molecules20192411218210.3390/molecules24112182 31185705
    [Google Scholar]
  165. LiJ. LongX. HuJ. BiJ. ZhouT. GuoX. HanC. HuangJ. WangT. XiongN. LinZ. Multiple pathways for natural product treatment of Parkinson’s disease: A mini review.Phytomedicine20196015295410.1016/j.phymed.2019.152954 31130327
    [Google Scholar]
  166. LouH. JingX. WeiX. ShiH. RenD. ZhangX. Naringenin protects against 6-OHDA-induced neurotoxicity via activation of the Nrf2/ARE signaling pathway.Neuropharmacology20147938038810.1016/j.neuropharm.2013.11.026 24333330
    [Google Scholar]
  167. KhatoonR. KaushikP. ParvezS. Mitochondria-related apoptosis regulation by minocycline: A study on a transgenic Drosophila Model of Alzheimer’s Disease.ACS Omega2022723191061911210.1021/acsomega.1c05653 35721948
    [Google Scholar]
  168. VarshneyV. GarabaduD. Ang(1–7) exerts Nrf2-mediated neuroprotection against amyloid beta-induced cognitive deficits in rodents.Mol. Biol. Rep.20214854319433110.1007/s11033‑021‑06447‑1 34075536
    [Google Scholar]
  169. GhofraniS. JoghataeiM.T. MohseniS. BaluchnejadmojaradT. BagheriM. KhamseS. RoghaniM. Naringenin improves learning and memory in an Alzheimer’s disease rat model: Insights into the underlying mechanisms.Eur. J. Pharmacol.201576419520110.1016/j.ejphar.2015.07.001 26148826
    [Google Scholar]
  170. ManiS. SekarS. BarathidasanR. ManivasagamT. ThenmozhiA.J. SevananM. ChidambaramS.B. EssaM.M. GuilleminG.J. SakharkarM.K. Naringenin decreases α-synuclein expression and neuroinflammation in MPTP-induced Parkinson’s disease model in mice.Neurotox. Res.201833365667010.1007/s12640‑018‑9869‑3 29427283
    [Google Scholar]
  171. GabaB. KhanT. HaiderM.F. AlamT. BabootaS. ParvezS. AliJ. Vitamin E loaded naringenin nanoemulsion via intranasal de- livery for the management of oxidative stress in a 6-OHDA Parkin- son’s disease model.BioMed Res. Int.2019201912010.1155/2019/2382563 31111044
    [Google Scholar]
  172. AhmadM.H. FatimaM. AliM. RizviM.A. MondalA.C. Naringenin alleviates paraquat-induced dopaminergic neuronal loss in SH-SY5Y cells and a rat model of Parkinson’s disease.Neuropharmacology202120110883110.1016/j.neuropharm.2021.108831
    [Google Scholar]
  173. MdS. GanS.Y. HawY.H. HoC.L. WongS. ChoudhuryH. In vitro neuroprotective effects of naringenin nanoemulsion against β-amyloid toxicity through the regulation of amyloidogenesis and tau phosphorylation. Int. J. Biol. Macromol., 2018118Pt A1211121910.1016/j.ijbiomac.2018.06.19030001606
    [Google Scholar]
  174. GhofraniS. JoghataeiM.T. MohseniS. BaluchnejadmojaradT. BagheriM. KhamseS. RoghaniM. Naringenin improves learning and memory in an Alzheimer’s disease rat model: Insights into the underlying mechanisms.Eur. J. Pharmacol.2015764195201
    [Google Scholar]
  175. SalmanM. SharmaP. AlamM.I. TabassumH. ParvezS. Naringenin mitigates behavioral alterations and provides neuroprotection against 3-nitropropinoic acid-induced Huntington’s disease like symptoms in rats.Nutr. Neurosci.2021202111 33856270
    [Google Scholar]
  176. ZhouT. LiuL. WangQ. GaoY. Naringenin alleviates cognition deficits in high‐fat diet‐fed SAMP8 mice.J. Food Biochem.2020449e1337510.1111/jfbc.13375 32677738
    [Google Scholar]
  177. SalmanM. SharmaP. AlamM.I. TabassumH. ParvezS. Naringenin mitigates behavioral alterations and provides neuroprotection against 3-nitropropinoic acid-induced Huntington’s disease like symptoms in rats.Nutr. Neurosci.2021202111 33856270
    [Google Scholar]
  178. Cicero-SarmientoC.G. Ortiz-AndradeR. Araujo-LeónJ.A. Segura-CamposM.R. Vazquez-GarciaP. Rubio-ZapataH. Hernández-BaltazarE. Yañez-PérezV. Sánchez-RecillasA. Sánchez-SalgadoJ.C. Hernández-NúñezE. Ruiz-CiauD. Preclinical safety profile of an oral naringenin/hesperidin dosage form by in vivo toxicological tests.Sci. Pharm.20229022810.3390/scipharm90020028
    [Google Scholar]
  179. LiP. WuH. WangY. PengW. SuW. Toxicological evaluation of naringin: Acute, subchronic, and chronic toxicity in Beagle dogs.Regul. Toxicol. Pharmacol.202011110458010.1016/j.yrtph.2020.104580 31954754
    [Google Scholar]
  180. LiP. WangS. GuanX. CenX. HuC. PengW. WangY. SuW. Six months chronic toxicological evaluation of naringin in Sprague–Dawley rats.Food Chem. Toxicol.201466657510.1016/j.fct.2014.01.023 24462649
    [Google Scholar]
  181. LiP. WangS. GuanX. LiuB. WangY. XuK. PengW. SuW. ZhangK. Acute and 13weeks subchronic toxicological evaluation of naringin in Sprague-Dawley rats.Food Chem. Toxicol.2013601910.1016/j.fct.2013.07.019 23871784
    [Google Scholar]
  182. GreenwayF. Effect of Naringenin and Beta Carotene on Energy Expenditure.2021Available From: https://classic.clinicaltrials.gov/ct2/show/study/NCT04697355?cond=naringenin&draw=2&rank=1
    [Google Scholar]
  183. RebelloC. Safety and pharmacokinetics of an extract of Naringenin (Citrus).2020Available From: https://classic.clinicaltrials.gov/ct2/show/NCT03582553?cond=naringenin&draw=2&rank=2
    [Google Scholar]
  184. ArthurY. A pilot study of the grapefruit flavonoid naringenin for HCV infection.2013Available From: https://classic.clinicaltrials.gov/ct2/show/results/NCT01091077?cond=naringenin&draw=2&rank=3
    [Google Scholar]
  185. GalluzziS. Clinical and biological effects of citrus-phytochemicals in subjective cognitive decline.2021Available From: https://classic.clinicaltrials.gov/ct2/show/NCT04744922?cond=naringenin&draw=2&rank=4
    [Google Scholar]
  186. ClaudeD.U.B.R.A.Y. Effects of a long-term grapefruit juice consumption on vascular protection and bone metabolism.2011Available From: https://classic.clinicaltrials.gov/ct2/show/NCT01272167?cond=NCT01272167&draw=2&rank=1
    [Google Scholar]
  187. JoëlC.O.N.S.T.A.N.S. Effects of regular and consequent citrus fruits consumption on vascular protection (AGRUVASC).2008Available From: https://classic.clinicaltrials.gov/ct2/show/NCT00539916?cond=NCT00539916&draw=2&rank=1
    [Google Scholar]
  188. FuS. ZhangY. ShiJ. HaoD. ZhangP. Identification of gene-phenotype connectivity associated with flavanone naringenin by functional network analysis.PeerJ20197e661110.7717/peerj.6611 30918758
    [Google Scholar]
  189. SmruthiM.R. NallamuthuI. AnandT. A comparative study of optimized naringenin nanoformulations using nano-carriers (PLA/PVA and zein/pectin) for improvement of bioavailability.Food Chem.202236913095010.1016/j.foodchem.2021.130950 34474288
    [Google Scholar]
  190. NouriZ. FakhriS. El-SendunyF.F. SanadgolN. Abd-ElGhaniG.E. FarzaeiM.H. ChenJ.T. On the neuroprotective effects of naringenin: Pharmacological targets, signaling pathways, molecular mechanisms, and clinical perspective.Biomolecules201991169010.3390/biom9110690 31684142
    [Google Scholar]
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