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2000
Volume 30, Issue 36
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Chronic venous disease (CVD) significantly impacts global health, presenting a complex challenge in medical management. Despite its prevalence and the burden it places on healthcare systems, CVD remains underdiagnosed and undertreated. This review aims to provide a comprehensive analysis of the bioactive compounds in the genus, exploring their therapeutic potential in CVD treatment and addressing the gap in current treatment modalities. A narrative review methodology was adopted, focusing on the pharmacological effects of -derived bioactive compounds, including flavonoids and terpenes. Additionally, the review introduced the DBsimilarity method for analyzing the chemical space and structural similarities among compounds. The review highlights the genus as a rich source of pharmacologically active compounds, notably flavonoids and terpenes, which exhibit significant anti-inflammatory, antioxidant, and veno-protective properties. Some of these compounds have been integrated into existing therapies, underscoring their potential for CVD management. The DBsimilarity analysis further identified many clusters of compounds with more than 85% structural similarity. -derived bioactive compounds offer promising therapeutic potential for managing CVD, showcasing significant anti-inflammatory, antioxidant, and veno-protective effects. The need for further comparative studies, as well as safety and efficacy investigations specific to CVD treatment, is evident. This review underlines the importance of advancing our understanding of these natural compounds and encouraging the development of novel treatments and formulations for effective CVD management. The DBsimilarity method's introduction provides a novel approach to exploring the chemical diversity within the genus, opening new pathways for pharmacological research.

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References

  1. EklofB. PerrinM. DelisK.T. RutherfordR.B. GloviczkiP. American Venous Forum European Venous Forum International Union of Phlebology American College of Phlebology International Union of Angiology Updated terminology of chronic venous disorders: The VEIN-TERM transatlantic interdisciplinary consensus document.J. Vasc. Surg.200949249850110.1016/j.jvs.2008.09.01419216970
    [Google Scholar]
  2. De MaeseneerM.G. KakkosS.K. AherneT. BaekgaardN. BlackS. BlomgrenL. GiannoukasA. GohelM. de GraafR. Hamel-DesnosC. JawienA. Jaworucka-KaczorowskaA. LattimerC.R. MostiG. NoppeneyT. van RijnM.J. StansbyG. KolhP. Bastos GoncalvesF. ChakféN. CoscasR. de BorstG.J. DiasN.V. HinchliffeR.J. KoncarI.B. LindholtJ.S. TrimarchiS. TulamoR. TwineC.P. VermassenF. WanhainenA. Document Reviewers BjörckM. LabropoulosN. LurieF. MansilhaA. NyamekyeI.K. Ramirez OrtegaM. UlloaJ.H. UrbanekT. van RijA.M. VuylstekeM.E. ESVS Guidelines Committee Editor’s choice- European Society for Vascular Surgery (ESVS) 2022 clinical practice guidelines on the management of chronic venous disease of the lower limbs.Eur. J. Vasc. Endovasc. Surg.202263218426710.1016/j.ejvs.2021.12.02435027279
    [Google Scholar]
  3. LattimerC.R. CVD: A condition of underestimated severity.Int. Angiol.201433322222824732585
    [Google Scholar]
  4. RabeE. GuexJ.J. PuskasA. ScuderiA. Fernandez QuesadaF. VCP Coordinators Epidemiology of chronic venous disorders in geographically diverse populations: Results from the Vein Consult Program.Int. Angiol.201231210511522466974
    [Google Scholar]
  5. OrtegaM.A. Fraile-MartínezO. García-MonteroC. Álvarez-MonM.A. ChaowenC. Ruiz-GrandeF. PekarekL. MonserratJ. AsúnsoloA. García-HonduvillaN. Álvarez-MonM. BujanJ. Understanding chronic venous disease: A critical overview of its pathophysiology and medical management.J. Clin. Med.20211015323910.3390/jcm1015323934362022
    [Google Scholar]
  6. EvansC.J. FowkesF.G. RuckleyC.V. LeeA.J. Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study.J. Epidemiol. Community Health199953314915310.1136/jech.53.3.14910396491
    [Google Scholar]
  7. LeeA.J. RobertsonL.A. BoghossianS.M. AllanP.L. RuckleyC.V. FowkesF.G.R. EvansC.J. Progression of varicose veins and chronic venous insufficiency in the general population in the Edinburgh Vein Study.J. Vasc. Surg. Venous Lymphat. Disord.201531182610.1016/j.jvsv.2014.09.00826993676
    [Google Scholar]
  8. BerganJ.J. Schmid-SchönbeinG.W. SmithP.D.C. NicolaidesA.N. BoisseauM.R. EklofB. Chronic venous disease.N. Engl. J. Med.2006355548849810.1056/NEJMra05528916885552
    [Google Scholar]
  9. SantiagoF.R. UlloaJ. RégnierC. PeudonT. BraundE. Fradet-AubignatC. GianesiniS. The impact of lower limb chronic venous disease on quality of life: Patient and physician perspectives.J. Comp. Eff. Res.2022111178980310.2217/cer‑2022‑005435642553
    [Google Scholar]
  10. BrandF.N. DannenbergA.L. AbbottR.D. KannelW.B. The epidemiology of varicose veins: The Framingham Study.Am. J. Prev. Med.1988429610110.1016/S0749‑3797(18)31203‑03395496
    [Google Scholar]
  11. Castro-FerreiraR. CardosoR. Leite-MoreiraA. MansilhaA. The role of endothelial dysfunction and inflammation in chronic venous disease.Ann. Vasc. Surg.20184638039310.1016/j.avsg.2017.06.13128688874
    [Google Scholar]
  12. LabropoulosN. How does chronic venous disease progress from the first symptoms to the advanced stages? A review.Adv. Ther.201936S1Suppl. 1131910.1007/s12325‑019‑0885‑330758741
    [Google Scholar]
  13. TakaseS. BerganJ.J. Schmid-SchönbeinG. Expression of adhesion molecules and cytokines on saphenous veins in chronic venous insufficiency.Ann. Vasc. Surg.200014542743510.1007/s10016991009210990550
    [Google Scholar]
  14. TakaseS. Schmid-SchönbeinG. BerganJ.J. Leukocyte activation in patients with venous insufficiency.J. Vasc. Surg.199930114815610.1016/S0741‑5214(99)70187‑410394165
    [Google Scholar]
  15. SaharayM. ShieldsD.A. GeorgiannosS.N. PorterJ.B. ScurrJ.H. Coleridge SmithP.D. Endothelial activation in patients with chronic venous disease.Eur. J. Vasc. Endovasc. Surg.199815434234910.1016/S1078‑5884(98)80039‑79610348
    [Google Scholar]
  16. TisatoV. ZauliG. VoltanR. GianesiniS. di IasioM.G. VolpiI. FiorentiniG. ZamboniP. SecchieroP. Endothelial cells obtained from patients affected by chronic venous disease exhibit a pro-inflammatory phenotype.PLoS One201276e3954310.1371/journal.pone.003954322737245
    [Google Scholar]
  17. SaharayM. ShieldsD.A. PorterJ.B. ScurrJ.H. Coleridge SmithP.D. Leukocyte activity in the microcirculation of the leg in patients with chronic venous disease.J. Vasc. Surg.199726226527310.1016/S0741‑5214(97)70188‑59279314
    [Google Scholar]
  18. SerralheiroP. SoaresA. Costa AlmeidaC. VerdeI. TGF-β1 in vascular wall pathology: Unraveling chronic venous insufficiency pathophysiology.Int. J. Mol. Sci.20171812253410.3390/ijms1812253429186866
    [Google Scholar]
  19. KomarówW. HawroP. LekstonA. UrbanekT. ZagrodzkiP. Endothelial dysfunction in patients with chronic venous disease: An evaluation based on the flow-mediated dilatation test.Int. Angiol.2015341364225027597
    [Google Scholar]
  20. MaticP. JolicS. TanaskovicS. SoldatovicI. KatsikiN. IsenovicE. RadakD. Chronic venous disease and comorbidities.Angiology201566653954410.1177/000331971454198825005764
    [Google Scholar]
  21. NicolaidesA. KakkosS. BaekgaardN. ComerotaA. de MaeseneerM. EklofB. GiannoukasA.D. LugliM. MaletiO. MyersK. NelzénO. PartschH. PerrinM. Management of chronic venous disorders of the lower limbs. Guidelines according to scientific evidence. Part I.Int. Angiol.201837318125410.23736/S0392‑9590.18.03999‑829871479
    [Google Scholar]
  22. BogachevV.Y. BoldinB.V. LobanovV.N. Benefits of micronized purified flavonoid fraction as adjuvant therapy on inflammatory response after sclerotherapy.Int. Angiol.2018371717810.23736/S0392‑9590.17.03868‑828945060
    [Google Scholar]
  23. YiannakopoulouE. Safety concerns for sclerotherapy of telangiectases, reticular and varicose veins.Pharmacology2016981-2626910.1159/00044543627104778
    [Google Scholar]
  24. RameletA.A. BoisseauM.R. AllegraC. NicolaidesA. JaegerK. CarpentierP. CappelliR. ForconiS. Veno-active drugs in the management of chronic venous disease. An international consensus statement: Current medical position, prospective views and final resolution.Clin. Hemorheol. Microcirc.200533430931916317240
    [Google Scholar]
  25. ChenH. ShenY. ZhangH. LongX. DengK. XuT. LiY. Clinical application of polylactic acid/gelatin nanofibre membrane in hard-to-heal lower extremity venous ulcers.J. Wound Care2022311193094010.12968/jowc.2022.31.11.93036367804
    [Google Scholar]
  26. GibelloL. D’AnticoS. SalafiaM. SenettaR. PomattoM.A.C. OrlandoG. SarcinellaA. LopatinaT. QuaglinoP. LorenziM. VerziniF. CamussiG. BrizziM.F. First pilot case-control interventional study using autologous extracellular vesicles to treat chronic venous ulcers unresponsive to conventional treatments.Pharmacol. Res.202319010671810.1016/j.phrs.2023.10671836878306
    [Google Scholar]
  27. NoceraR. ElettoD. SantoroV. ParisiV. BelloneM.L. IzzoM. ToscoA. Dal PiazF. DonadioG. De TommasiN. Design of an herbal preparation composed by a combination of Ruscus aculeatus L. and Vitis vinifera L. extracts, magnolol and diosmetin to address chronic venous diseases through an anti-inflammatory effect and AP-1 modulation.Plants2023125105110.3390/plants1205105136903912
    [Google Scholar]
  28. SeoM.G. JoM.J. HongN.I. KimM.J. ShimK.S. ShinE. LeeJ.J. ParkS.J. Anti-inflammatory and anti-vascular leakage effects by combination of Centella asiatica and Vitis vinifera L. leaf extracts.Evid. Based Complement. Alternat. Med.2021202111810.1155/2021/738162033936244
    [Google Scholar]
  29. Benavente-GarcíaO. CastilloJ. Update on uses and properties of Citrus flavonoids: New findings in anticancer, cardiovascular, and anti-inflammatory activity.J. Agric. Food Chem.200856156185620510.1021/jf800656818593176
    [Google Scholar]
  30. JaM. Manthey JA, Guthrie N, Grohmann K. Biological properties of citrus flavonoids pertaining to cancer and inflammation.Curr. Med. Chem.20018213553https://pubmed.ncbi.nlm.nih.gov/11172671/[Internet].
    [Google Scholar]
  31. MahmoudA.M. Hernández BautistaR.J. SandhuM.A. HusseinO.E. Beneficial effects of Citrus flavonoids on cardiovascular and metabolic health.Oxid. Med. Cell. Longev.2019201911910.1155/2019/548413830962863
    [Google Scholar]
  32. SainiR.K. RanjitA. SharmaK. PrasadP. ShangX. GowdaK.G.M. KeumY.S. Bioactive compounds of Citrus fruits: A review of composition and health benefits of carotenoids, flavonoids, limonoids, and terpenes.Antioxidants202211223910.3390/antiox1102023935204122
    [Google Scholar]
  33. ZibaeeE. KamalianS. TajvarM. AmiriM.S. RamezaniM. MoghadamA.T. EmamiS.A. SahebkarA. Citrus species: A review of traditional uses, phytochemistry and pharmacology.Curr. Pharm. Des.2020261449710.2174/138161282566619112711560131775593
    [Google Scholar]
  34. DuarteA. FernandesJ. BernardesJ. Citrus as a component of the mediterranean diet.J. Spatial Organ Dyn20164289304
    [Google Scholar]
  35. Flora e Funga do Brasil.Available from: https://floradobrasil.jbrj.gov.br (accessed on 7-7-2024)
  36. ChhikaraN. KourR. JaglanS. GuptaP. GatY. PanghalA. Citrus medica: Nutritional, phytochemical composition and health benefits – A review.Food Funct.2018941978199210.1039/C7FO02035J29594287
    [Google Scholar]
  37. Citrus maxima (Burm.)Available from: https://floradobrasil.jbrj.gov.br (accessed on 7-7-2024)
  38. Citrus aurantium L. Available from: https://floradobrasil.jbrj.gov.br (accessed on 7-7-2024)
  39. Braverman JB. Citrus products chemical composition and chemical technology. Interscience Publishers, INC., New York Interscience Publishers LTD., London; 1949.
  40. Mandioca e Fruticultura. Citros.Available from: https://www.embrapa.br (accessed on 7-7-2024)
  41. KhanU.M. SameenA. AadilR.M. ShahidM. SezenS. ZarrabiA. OzdemirB. SevindikM. KaplanD.N. SelamogluZ. YdyrysA. AnithaT. KumarM. Sharifi-RadJ. ButnariuM. Citrus genus and its waste utilization: A review on health-promoting activities and industrial application.Evid. Based Complement. Alternat. Med.2021202111710.1155/2021/248880434795782
    [Google Scholar]
  42. LiuY. HeyingE. TanumihardjoS.A. History, global distribution, and nutritional importance of Citrus fruits.Compr. Rev. Food Sci. Food Saf.201211653054510.1111/j.1541‑4337.2012.00201.x
    [Google Scholar]
  43. ChenR. QiQ.L. WangM.T. LiQ.Y. Therapeutic potential of naringin: An overview.Pharm. Biol.201654123203321010.1080/13880209.2016.121613127564838
    [Google Scholar]
  44. LuY. ZhangC. BucheliP. WeiD. Citrus flavonoids in fruit and traditional Chinese medicinal food ingredients in China.Plant Foods Hum. Nutr.2006612556310.1007/s11130‑006‑0014‑816816988
    [Google Scholar]
  45. PancheA.N. DiwanA.D. ChandraS.R. Flavonoids: An overview.J. Nutr. Sci.20165e4710.1017/jns.2016.4128620474
    [Google Scholar]
  46. Benavente-GarcíaO. CastilloJ. MarinF.R. OrtuñoA. Del RíoJ.A. Uses and properties of citrus flavonoids.J. Agric. Food Chem.199745124505451510.1021/jf970373s18593176
    [Google Scholar]
  47. LiC. DuG-H. Diosmin. Natural small molecule drugs from plants.SingaporeSpringer, Singapore2018656910.1007/978‑981‑10‑8022‑7_10
    [Google Scholar]
  48. NicolaidesA.N. The benefits of micronized purified flavonoid fraction (MPFF) throughout the progression of chronic venous disease.Adv. Ther.202037S1Suppl. 11510.1007/s12325‑019‑01218‑831970659
    [Google Scholar]
  49. VictorM.M. DavidJ.M. CortezM.V.M. LeiteJ.L. da SilvaG.S.B. A high-yield process for extraction of hesperidin from orange (Citrus sinensis L. osbeck) peels waste, and its transformation to diosmetin, a valuable and bioactive flavonoid.Waste Biomass Valoriz.202112131332010.1007/s12649‑020‑00982‑x
    [Google Scholar]
  50. BoguckaK.A Diosmin – isolation techniques, determination in plant material and pharmaceutical formulations, and clinical use.Nat. Prod. Commun.201381934578X1300800
    [Google Scholar]
  51. HuwaitE. MobashirM. Potential and therapeutic roles of diosmin in human diseases.Biomedicines2022105107610.3390/biomedicines1005107635625813
    [Google Scholar]
  52. MustafaS. AkbarM. KhanM.A. SunitaK. ParveenS. PawarJ.S. MasseyS. AgarwalN.R. HusainS.A. Plant metabolite diosmin as the therapeutic agent in human diseases.Curr. Res. Pharmacol. Drug Disc.2022310012210.1016/j.crphar.2022.10012236568270
    [Google Scholar]
  53. ImamF. Al-HarbiN.O. Al-HarbiM.M. AnsariM.A. ZoheirK.M.A. IqbalM. AnwerM.K. Al HoshaniA.R. AttiaS.M. AhmadS.F. Diosmin downregulates the expression of T cell receptors, pro-inflammatory cytokines and NF-κB activation against LPS-induced acute lung injury in mice.Pharmacol. Res.201510211110.1016/j.phrs.2015.09.00126361726
    [Google Scholar]
  54. FeldoM. Wójciak-KosiorM. SowaI. KockiJ. BoguckiJ. ZubilewiczT. KęsikJ. Bogucka-KockaA. Effect of diosmin administration in patients with chronic venous disorders on selected factors affecting angiogenesis.Molecules20192418331610.3390/molecules2418331631547271
    [Google Scholar]
  55. ŞimşekE. KoçakO. YıldırımK. KuruoğluA. TaşkınN.D. BozkurtS. İmirN. AtaşC. AkçitE.T. ÇobanM. ÇobanA.Y. The anti-angiogenic and anti-microbial effect of diosmin: Potential receptor interactions via molecular docking.Rev. Bras. Farmacogn.202333242243110.1007/s43450‑023‑00365‑y
    [Google Scholar]
  56. ShalkamiA.S. HassanM.I.A. BakrA.G. Anti-inflammatory, antioxidant and anti-apoptotic activity of diosmin in acetic acid-induced ulcerative colitis.Hum. Exp. Toxicol.2018371788610.1177/096032711769407529187079
    [Google Scholar]
  57. Abdel-ReheM.A. MessihaB.A.S. Abo-SaifA.A. Hepatoprotective effect of diosmin on iron-induced liver damage.Int. J. Pharmacol.201713652954010.3923/ijp.2017.529.540
    [Google Scholar]
  58. CyprianiB. LimassetB. CarriéM.L. Le DoucenC. RoussieM. De PauletA. DamonM. Antioxidant activity of micronized diosmin on oxygen species from stimulated human neutrophils.Biochem. Pharmacol.19934571531153510.1016/0006‑2952(93)90056‑38385947
    [Google Scholar]
  59. SilambarasanT. RajaB. Diosmin, a bioflavonoid reverses alterations in blood pressure, nitric oxide, lipid peroxides and antioxidant status in DOCA-salt induced hypertensive rats.Eur. J. Pharmacol.20126791-3818910.1016/j.ejphar.2011.12.04022266490
    [Google Scholar]
  60. AraujoD. VianaF. OsswaldW. Diosmin therapy alters the metabolism of noradrenaline by the varicose human saphenous vein.Pharmacol. Res.199124325325610.1016/1043‑6618(91)90088‑F1956869
    [Google Scholar]
  61. RefaatJ. YehiaS. RamadanA. Rhoifolin: A review of sources and biological activities. Int J Pharmacogn20152102109
    [Google Scholar]
  62. EldahshanO.A. AzabS.S. Anti-inflammatory effect of apigenin-7- neohesperidoside (rhoifolin) in carrageenin-induced rat oedema model.JAPS2012287479
    [Google Scholar]
  63. NegmW.A. El-KademA.H. ElekhnawyE. AttallahN.G.M. Al-HamoudG.A. El-MasryT.A. ZayedA. Wound-healing potential of rhoifolin-rich fraction isolated from Sanguisorba officinalis roots supported by enhancing re-epithelization, angiogenesis, anti-inflammatory, and antimicrobial effects.Pharmaceuticals202215217810.3390/ph1502017835215291
    [Google Scholar]
  64. PengS. HuC. LiuX. LeiL. HeG. XiongC. WuW. Rhoifolin regulates oxidative stress and proinflammatory cytokine levels in Freund’s adjuvant-induced rheumatoid arthritis via inhibition of NF-κB.Braz. J. Med. Biol. Res.2020536e948910.1590/1414‑431x20209489
    [Google Scholar]
  65. RizzaS. MuniyappaR. IantornoM. KimJ. ChenH. PullikotilP. SeneseN. TesauroM. LauroD. CardilloC. QuonM.J. Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing inflammatory markers in patients with metabolic syndrome.J. Clin. Endocrinol. Metab.2011965E782E79210.1210/jc.2010‑287921346065
    [Google Scholar]
  66. KaretováD. SuchopárJ. BultasJ. Diosmin/hesperidin: A cooperating tandem, or is diosmin crucial and hesperidin an inactive ingredient only?Vnitr. Lek.20206629710310.36290/vnl.2020.01632942884
    [Google Scholar]
  67. WilmsenP.K. SpadaD.S. SalvadorM. Antioxidant activity of the flavonoid hesperidin in chemical and biological systems.J. Agric. Food Chem.200553124757476110.1021/jf050200015941311
    [Google Scholar]
  68. HirataA. MurakamiY. ShojiM. KadomaY. FujisawaS. Kinetics of radical-scavenging activity of hesperetin and hesperidin and their inhibitory activity on COX-2 expression.Anticancer Res.20052553367337416101151
    [Google Scholar]
  69. KimG.D. Hesperidin inhibits vascular formation by blocking the AKT/mTOR signaling pathways.Prev. Nutr. Food Sci.201520422122910.3746/pnf.2015.20.4.22126770908
    [Google Scholar]
  70. HabauzitV. SaccoS.M. Gil-IzquierdoA. TrzeciakiewiczA. MorandC. BarronD. PinaudS. OffordE. HorcajadaM.N. Differential effects of two citrus flavanones on bone quality in senescent male rats in relation to their bioavailability and metabolism.Bone20114951108111610.1016/j.bone.2011.07.03021820093
    [Google Scholar]
  71. Cavia-SaizM. BustoM.D. Pilar-IzquierdoM.C. OrtegaN. Perez- MateosM. MuñizP. Antioxidant properties, radical scavenging activity and biomolecule protection capacity of flavonoid naringenin and its glycoside naringin: A comparative study.J. Sci. Food Agric.20109071238124410.1002/jsfa.395920394007
    [Google Scholar]
  72. BacanlıM. BaşaranA.A. BaşaranN. The antioxidant and antigenotoxic properties of citrus phenolics limonene and naringin.Food Chem. Toxicol.20158116017010.1016/j.fct.2015.04.01525896273
    [Google Scholar]
  73. LiQ. WangY. ZhangL. ChenL. DuY. YeT. ShiX. Naringenin exerts anti-angiogenic effects in human endothelial cells: Involvement of ERRα/VEGF/KDR signaling pathway.Fitoterapia2016111788610.1016/j.fitote.2016.04.01527105956
    [Google Scholar]
  74. RustamM. IforaI. FauziahF. Potential anti-inflammatory effects of eriocitrin: A review.J. Drug Deliv. Ther.202212318719210.22270/jddt.v12i3.5456
    [Google Scholar]
  75. XuJ. MaL. FuP. Eriocitrin attenuates ischemia reperfusion-induced oxidative stress and inflammation in rats with acute kidney injury by regulating the dual-specificity phosphatase 14 (DUSP14)-mediated Nrf2 and nuclear factor-κB (NF-κB) pathways.Ann. Transl. Med.20219435035010.21037/atm‑21‑33733708977
    [Google Scholar]
  76. LiuJ. HuangH. HuangZ. MaY. ZhangL. HeY. LiD. LiuW. GoodinS. ZhangK. ZhengX. Eriocitrin in combination with resveratrol ameliorates LPS-induced inflammation in RAW264.7 cells and relieves TPA-induced mouse ear edema.J. Funct. Foods20195632133210.1016/j.jff.2019.03.008
    [Google Scholar]
  77. GuoG. ShiW. ShiF. GongW. LiF. ZhouG. SheJ. Anti-inflammatory effects of eriocitrin against the dextran sulfate sodium–induced experimental colitis in murine model.J. Biochem. Mol. Toxicol.20193311e2240010.1002/jbt.2240031593355
    [Google Scholar]
  78. HeJ. ZhouD. YanB. Eriocitrin alleviates oxidative stress and inflammatory response in cerebral ischemia reperfusion rats by regulating phosphorylation levels of Nrf2/NQO-1/HO-1/NF-κB p65 proteins.Ann. Transl. Med.202081275710.21037/atm‑20‑4258
    [Google Scholar]
  79. DenaroM. SmeriglioA. TrombettaD. Antioxidant and anti-inflammatory activity of citrus flavanones mix and its stability after in vitro simulated digestion.Antioxidants202110214010.3390/antiox1002014033498195
    [Google Scholar]
  80. YaoL. LiuW. BashirM. NisarM.F. WanC.C. Eriocitrin: A review of pharmacological effects.Biomed. Pharmacother.202215411356310.1016/j.biopha.2022.11356335987162
    [Google Scholar]
  81. TakaseT. IkeuchiS. InoueT. MukaiR. Eriocitrin contained in lemon peel ameliorates disuse muscle atrophy by suppressing the expression of atrogin-1 and murf-1 in denervated mice.J. Nat. Prod.20218472048205210.1021/acs.jnatprod.1c0027134189920
    [Google Scholar]
  82. MiyakeY. ShimoiK. KumazawaS. YamamotoK. KinaeN. OsawaT. Identification and antioxidant activity of flavonoid metabolites in plasma and urine of eriocitrin-treated rats.J. Agric. Food Chem.20004883217322410.1021/jf990994g10956094
    [Google Scholar]
  83. ComaladaM. CamuescoD. SierraS. BallesterI. XausJ. GálvezJ. ZarzueloA. In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-κB pathway.Eur. J. Immunol.200535258459210.1002/eji.20042577815668926
    [Google Scholar]
  84. BootsA.W. WilmsL.C. SwennenE.L.R. KleinjansJ.C.S. BastA. HaenenG.R.M.M. In vitro and ex vivo anti-inflammatory activity of quercetin in healthy volunteers.Nutrition2008247-870371010.1016/j.nut.2008.03.02318549926
    [Google Scholar]
  85. KleemannR. VerschurenL. MorrisonM. ZadelaarS. van ErkM.J. WielingaP.Y. KooistraT. Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models.Atherosclerosis20112181445210.1016/j.atherosclerosis.2011.04.02321601209
    [Google Scholar]
  86. HollmanP.C.H. van TrijpJ.M.P. MengelersM.J.B. de VriesJ.H.M. KatanM.B. Bioavailability of the dietary antioxidant flavonol quercetin in man.Cancer Lett.19971141-213914010.1016/S0304‑3835(97)04644‑29103273
    [Google Scholar]
  87. BaghelS. ShrivastavaN. BaghelP. A review of quercetin: Antioxidant and anticancer properties.World J. Pharm. Pharm. Sci.20121146160
    [Google Scholar]
  88. SakanashiY. OyamaK. MatsuiH. OyamaT.B. OyamaT.M. NishimuraY. SakaiH. OyamaY. Possible use of quercetin, an antioxidant, for protection of cells suffering from overload of intracellular Ca2+: A model experiment.Life Sci.2008835-616416910.1016/j.lfs.2008.05.00918586279
    [Google Scholar]
  89. BootsA.W. HaenenG.R.M.M. BastA. Health effects of quercetin: From antioxidant to nutraceutical.Eur. J. Pharmacol.20085852-332533710.1016/j.ejphar.2008.03.00818417116
    [Google Scholar]
  90. TanW. LinL. LiM. ZhangY.X. TongY. XiaoD. DingJ. Quercetin, a dietary-derived flavonoid, possesses antiangiogenic potential.Eur. J. Pharmacol.20034592-325526210.1016/S0014‑2999(02)02848‑012524154
    [Google Scholar]
  91. IguraK. OhtaT. KurodaY. KajiK. Resveratrol and quercetin inhibit angiogenesis in vitro.Cancer Lett.20011711111610.1016/S0304‑3835(01)00443‑811485823
    [Google Scholar]
  92. YooH. KuS.K. BaekY.D. BaeJ.S. Anti-inflammatory effects of rutin on HMGB1-induced inflammatory responses in vitro and in vivo.Inflamm. Res.201463319720610.1007/s00011‑013‑0689‑x24292859
    [Google Scholar]
  93. YangJ. GuoJ. YuanJ. In vitro antioxidant properties of rutin.Lebensm. Wiss. Technol.20084161060106610.1016/j.lwt.2007.06.010
    [Google Scholar]
  94. ChoiS.S. ParkH.R. LeeK.A. A comparative study of rutin and rutin glycoside: Antioxidant activity, anti-inflammatory effect, effect on platelet aggregation and blood coagulation.Antioxidants20211011169610.3390/antiox1011169634829567
    [Google Scholar]
  95. MatsubaraK. IshiharaK. MizushinaY. MoriM. NakajimaN. Anti-angiogenic activity of quercetin and its derivatives.Lett. Drug Des. Discov.20041432933310.2174/1570180043398533
    [Google Scholar]
  96. ZibernaL. TramerF. MozeS. VrhovsekU. MattiviF. PassamontiS. Transport and bioactivity of cyanidin 3-glucoside into the vascular endothelium.Free Radic. Biol. Med.20125291750175910.1016/j.freeradbiomed.2012.02.02722387282
    [Google Scholar]
  97. XuJ.W. IkedaK. YamoriY. Upregulation of endothelial nitric oxide synthase by cyanidin-3-glucoside, a typical anthocyanin pigment.Hypertension200444221722210.1161/01.HYP.0000135868.38343.c615226277
    [Google Scholar]
  98. TrineiM. CarpiA. Menabo’R. StortoM. FornariM. MarinelliA. MinardiS. RiboniM. CasciaroF. DiLisaF. PetroniK. TonelliC. GiorgioM. Dietary intake of cyanidin-3-glucoside induces a long-lasting cardioprotection from ischemia/reperfusion injury by altering the microbiota.J. Nutr. Biochem.202210110892110.1016/j.jnutbio.2021.10892134864150
    [Google Scholar]
  99. AminH. The vascular and anti-inflammatory activity of Cyanidin-3-Glucoside and its metabolites in human vascular endothelial cells.Doctor of Philosophy, University of East Anglia. Norwich Medical School, 2015.
    [Google Scholar]
  100. WangH. NairM.G. StrasburgG.M. ChangY.C. BoorenA.M. GrayJ.I. DeWittD.L. Antioxidant and antiinflammatory activities of anthocyanins and their aglycon, cyanidin, from tart cherries.J. Nat. Prod.199962229429610.1021/np980501m10075763
    [Google Scholar]
  101. ZhangY. WangX. WangY. LiuY. XiaM. Supplementation of cyanidin-3-O-β-glucoside promotes endothelial repair and prevents enhanced atherogenesis in diabetic apolipoprotein E-deficient mice.J. Nutr.201314381248125310.3945/jn.113.17745123761653
    [Google Scholar]
  102. EddinL.B. JhaN.K. MeeranM.F.N. KesariK.K. BeiramR. OjhaS. Neuroprotective potential of limonene and limonene containing natural products.Molecules20212615453510.3390/molecules2615453534361686
    [Google Scholar]
  103. 21 CFR 182.60 - Synthetic flavoring substances and adjuvants.Available from: https://www.ecfr.gov/current/title-21/part-182/section-182.60 (accessed on 7-7-2024)
  104. SunJ. D-Limonene: Safety and clinical applications.Altern. Med. Rev.200712325926418072821
    [Google Scholar]
  105. HirotaR. RogerN.N. NakamuraH. SongH.S. SawamuraM. SuganumaN. Anti-inflammatory effects of limonene from Yuzu (Citrus junos Tanaka) essential oil on eosinophils.J. Food Sci.2010753H87H9210.1111/j.1750‑3841.2010.01541.x20492298
    [Google Scholar]
  106. YuL. YanJ. SunZ. D-limonene exhibits anti-inflammatory and antioxidant properties in an ulcerative colitis rat model via regulation of iNOS, COX-2, PGE2 and ERK signaling pathways.Mol. Med. Rep.20171542339234610.3892/mmr.2017.624128260017
    [Google Scholar]
  107. AlSaffarR.M. RashidS. AhmadS.B. RehmanM.U. HussainI. Parvaiz AhmadS. GanaieM.A. D-limonene (5 (one-methyl-four-[1-methylethenyl]) cyclohexane) diminishes CCl4-induced cardiac toxicity by alleviating oxidative stress, inflammatory and cardiac markers.Redox Rep.2022271929910.1080/13510002.2022.206294735435141
    [Google Scholar]
  108. Chidambara MurthyK.N. JayaprakashaG.K. PatilB.S. D-limonene rich volatile oil from blood oranges inhibits angiogenesis, metastasis and cell death in human colon cancer cells.Life Sci.20129111-1242943910.1016/j.lfs.2012.08.01622935404
    [Google Scholar]
  109. BungauS.G. VesaC.M. BusteaC. PurzaA.L. TitD.M. BriscM.C. RaduA.F. Antioxidant and hypoglycemic potential of essential oils in diabetes mellitus and its complications.Int. J. Mol. Sci.202324221650110.3390/ijms24221650138003691
    [Google Scholar]
  110. FotiM.C. IngoldK.U. Mechanism of inhibition of lipid peroxidation by gamma-terpinene, an unusual and potentially useful hydrocarbon antioxidant.J. Agric. Food Chem.20035192758276510.1021/jf020993f12696969
    [Google Scholar]
  111. GuoY. BaschieriA. AmoratiR. ValgimigliL. Synergic antioxidant activity of γ-terpinene with phenols and polyphenols enabled by hydroperoxyl radicals.Food Chem.202134512846810.1016/j.foodchem.2020.12846833341300
    [Google Scholar]
  112. RamalhoT. Pacheco de OliveiraM. LimaA. Bezerra-SantosC. PiuvezamM. Gamma-terpinene modulates acute inflammatory response in mice.Planta Med.201581141248125410.1055/s‑0035‑154616926132854
    [Google Scholar]
  113. RamalhoT. FilgueirasL. Pacheco de OliveiraM. LimaA. Bezerra-SantosC. JancarS. PiuvezamM. Gamma-terpinene modulation of lps-stimulated macrophages is dependent on the PGE2/IL-10 axis.Planta Med.201682151341134510.1055/s‑0042‑10779927224271
    [Google Scholar]
  114. AsikinY. ShimizuK. IwasakiH. OkuH. WadaK. Stress amelioration and anti-inflammatory potential of Shiikuwasha (Citrus depressa Hayata) essential oil, limonene, and γ-terpinene.Yao Wu Shi Pin Fen Xi202230345446510.38212/2224‑6614.3414
    [Google Scholar]
  115. CarnesecchiS. Bras-GonçalvesR. BradaiaA. ZeiselM. GosséF. PouponM.F. RaulF. Geraniol, a component of plant essential oils, modulates DNA synthesis and potentiates 5-fluorouracil efficacy on human colon tumor xenografts.Cancer Lett.20042151535910.1016/j.canlet.2004.06.01915374632
    [Google Scholar]
  116. de CarvalhoK.I.M. BonaminF. dos SantosR.C. PéricoL.L. BeserraF.P. de SousaD.P. FilhoJ.M.B. da RochaL.R.M. Hiruma-LimaC.A. Geraniol-a flavoring agent with multifunctional effects in protecting the gastric and duodenal mucosa.Naunyn Schmiedebergs Arch. Pharmacol.2014387435536510.1007/s00210‑013‑0947‑z24337826
    [Google Scholar]
  117. Solórzano-SantosF. Miranda-NovalesM.G. Essential oils from aromatic herbs as antimicrobial agents.Curr. Opin. Biotechnol.201223213614110.1016/j.copbio.2011.08.00521903378
    [Google Scholar]
  118. Concentration-dependent Increase of murine P388 and B16 population doubling time by the acyclic monoterpene geraniol1, cancer research, American Association for Cancer Research. Available from: https://aacrjournals.org/cancerres/article/51/1/37/496428/Concentration-dependent-Increase-of-Murine-P388 (accessed on 7-7-2024)
  119. AmmarR.B. MohamedM.E. AlfwuairesM. Abdulaziz AlamerS. Bani IsmailM. VeeraraghavanV.P. SekarA.K. KsouriR. RajendranP. Anti-inflammatory activity of geraniol isolated from lemon grass on ox-ldl-stimulated endothelial cells by upregulation of heme oxygenase-1 via PI3K/Akt and Nrf-2 signaling pathways.Nutrients20221422481710.3390/nu1422481736432506
    [Google Scholar]
  120. El-BassossyH.M. ElberryA.A. GhareibS.A. Geraniol improves the impaired vascular reactivity in diabetes and metabolic syndrome through calcium channel blocking effect.J. Diabetes Complicat.20163061008101610.1016/j.jdiacomp.2016.04.00627131411
    [Google Scholar]
  121. PrasadS.N. MuralidharaM. Analysis of the antioxidant activity of geraniol employing various in-vitro models: Relevance to neurodegeneration in diabetic neuropathy.Asian J. Pharm. Clin. Res.201710710110.22159/ajpcr.2017.v10i7.18564
    [Google Scholar]
  122. WittigC. ScheuerC. ParakeningsJ. MengerM.D. LaschkeM.W. Geraniol suppresses angiogenesis by downregulating vascular endothelial growth factor (vegf)/vegfr-2 signaling.PLoS One2015107e013194610.1371/journal.pone.013194626154255
    [Google Scholar]
  123. RoyA. SarafS. Limonoids: Overview of significant bioactive triterpenes distributed in plants kingdom.Biol. Pharm. Bull.200629219120110.1248/bpb.29.19116462017
    [Google Scholar]
  124. MahmoudM.F. GamalS. El-FayoumiH.M. Limonin attenuates hepatocellular injury following liver ischemia and reperfusion in rats via toll-like receptor dependent pathway.Eur. J. Pharmacol.201474067668210.1016/j.ejphar.2014.06.01024967531
    [Google Scholar]
  125. ChenJ. LiuB.X. ShenQ. LiN. LingJ. XiaoM. JiaoH.Y. LiT. Limonin inhibits angiogenesis and metastasis of human breast cancer cells by suppressing the VEGFR2/IGFR1-mediated STAT3 signaling pathway.Transl. Cancer Res.20209116820683210.21037/tcr‑20‑199235117291
    [Google Scholar]
  126. ChenS.X. XiangJ.Y. HanJ.X. Yang-Feng LiH.Z. ChenH. XuM. Essential oils from spices inhibit cholinesterase activity and improve behavioral disorder in AlCl3 induced dementia.Chem. Biodivers.2022191e20210044310.1002/cbdv.20210044334855291
    [Google Scholar]
  127. BorgesR.M. de Assis FerreiraG. CamposM.M. TeixeiraA.M. das Neves CostaF. ChagasF.O. Data base similarity (DBsimilarity) of natural products to aid compound identification on MS and NMR pipelines, similarity networking, and more.Phytochem. Anal.20243519310110.1002/pca.327737592443
    [Google Scholar]
  128. LiJ. ZhaoR. MiaoP. XuF. ChenJ. JiangX. HuiZ. WangL. BaiR. Discovery of anti-inflammatory natural flavonoids: Diverse scaffolds and promising leads for drug discovery.Eur. J. Med. Chem.202326011579110.1016/j.ejmech.2023.11579137683361
    [Google Scholar]
  129. RakhaA. UmarN. RabailR. ButtM.S. KieliszekM. HassounA. AadilR.M. Anti-inflammatory and anti-allergic potential of dietary flavonoids: A review.Biomed. Pharmacother.202215611394510.1016/j.biopha.2022.11394536411631
    [Google Scholar]
  130. VerriW.A. VicentiniF.T.M.C. BaracatM.M. Flavonoids as anti-inflammatory and analgesic drugs: Mechanisms of action and perspectives in the development of pharmaceutical forms.Studies in Natural Products ChemistryElsevier2012
    [Google Scholar]
  131. NonesJ. e SpohrT.C.L.S. GomesF.C.A. Hesperidin, a flavone glycoside, as mediator of neuronal survival.Neurochem. Res.201136101776178410.1007/s11064‑011‑0493‑321553255
    [Google Scholar]
  132. RufinoA.T. RibeiroM. SousaC. JudasF. SalgueiroL. CavaleiroC. MendesA.F. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis.Eur. J. Pharmacol.201575014115010.1016/j.ejphar.2015.01.01825622554
    [Google Scholar]
  133. d’AlessioP.A. OstanR. BissonJ.F. SchulzkeJ.D. UrsiniM.V. BénéM.C. Oral administration of d-Limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans.Life Sci.20139224-261151115610.1016/j.lfs.2013.04.01323665426
    [Google Scholar]
  134. NishidaS. SatohH. Comparative vasodilating actions among terpenoids and flavonoids contained in Ginkgo biloba extract.Clin. Chim. Acta20043391-212913310.1016/j.cccn.2003.10.00414687903
    [Google Scholar]
  135. SuZ. WangC. ChangD. ZhuX. SaiC. PeiJ. Limonin attenuates the stemness of breast cancer cells via suppressing MIR216A methylation.Biomed. Pharmacother.201911210869910.1016/j.biopha.2019.10869930970511
    [Google Scholar]
  136. QuirogaP.R. NepoteV. BaumgartnerM.T. Contribution of organic acids to α-terpinene antioxidant activity.Food Chem.201927726727210.1016/j.foodchem.2018.10.10030502144
    [Google Scholar]
  137. HuangJ. FangZ. BaiC. MoY. LiuD. YangB. JiaX. FengL. Novel nano-encapsulated limonene: Utilization of drug-in-cyclodextrin-in-liposome formulation to improve the stability and enhance the antioxidant activity.Int. J. Pharm.202465312391410.1016/j.ijpharm.2024.12391438373597
    [Google Scholar]
  138. VieiraA.J. BeserraF.P. SouzaM.C. TottiB.M. RozzaA.L. Limonene: Aroma of innovation in health and disease.Chem. Biol. Interact.20182839710610.1016/j.cbi.2018.02.00729427589
    [Google Scholar]
  139. MoriwakiM. KitoK. NakagawaR. KapoorM.P. MatsumiyaY. FukuharaT. KobayashiJ. SatomotoK. YamagataH. KuroiwaY. Increased bioavailability of diosmetin-7-glucoside-γ-cyclodextrin inclusion complex compared with diosmin in Sprague-Dawley rats.Biosci. Biotechnol. Biochem.202387777177610.1093/bbb/zbad05137133406
    [Google Scholar]
  140. KanazeF.I. KokkalouE. GeorgarakisM. NiopasI. Validated high- performance liquid chromatographic method utilizing solid-phase extraction for the simultaneous determination of naringenin and hesperetin in human plasma.J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.2004801236336710.1016/j.jchromb.2003.11.03014751808
    [Google Scholar]
  141. BarfiB. AsghariA. RajabiM. BarfiA. SaeidiI. Simplified miniaturized ultrasound-assisted matrix solid phase dispersion extraction and high performance liquid chromatographic determination of seven flavonoids in citrus fruit juice and human fluid samples: Hesperetin and naringenin as biomarkers.J. Chromatogr. A20131311304010.1016/j.chroma.2013.08.07824011420
    [Google Scholar]
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  • Article Type: Review Article
Keyword(s): Citrus; diosmin; hesperidin; Rutaceae family; vascular diseases; venous insufficiency
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