Bioactive Compounds in Citrus Species with Potential for the Treatment of Chronic Venous Disease: A Review


Cite item

Full Text

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 Citrus 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 Citrus-derived bioactive compounds, including flavonoids and terpenes. Additionally, the review introduced the DBsimilarity method for analyzing the chemical space and structural similarities among Citrus compounds. The review highlights the Citrus 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. Citrus-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 Citrus genus, opening new pathways for pharmacological research.

About the authors

Vitória Almeida Silva

Faculdade de Farmácia, Universidade Federal do Rio de Janeiro

Email: info@benthamscience.net

Estefane de Freitas Pereira

Faculdade de Farmácia, Universidade Federal do Rio de Janeiro

Email: info@benthamscience.net

Juliana Ferreira

Faculdade de Farmácia, Universidade Federal do Rio de Janeiro

Email: info@benthamscience.net

Andrew Magno Teixeira

Instituto de Pesquisas de Produtos Naturais Walter Mors,, Universidade Federal do Rio de Janeiro

Email: info@benthamscience.net

Ricardo Borges

Instituto de Pesquisas de Produtos Naturais Walter Mors, Universidade Federal do Rio de Janeiro

Email: info@benthamscience.net

Luiz Cláudio da Silva

Faculdade de Farmácia,, Universidade Federal do Rio de Janeiro

Author for correspondence.
Email: info@benthamscience.net

References

  1. Eklof B, Perrin M, Delis KT, Rutherford RB, Gloviczki P. Updated terminology of chronic venous disorders: The VEIN-TERM transatlantic interdisciplinary consensus document. J Vasc Surg 2009; 49(2): 498-501. doi: 10.1016/j.jvs.2008.09.014 PMID: 19216970
  2. De Maeseneer MG, Kakkos SK, Aherne T, et al. 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 2022; 63(2): 184-267. doi: 10.1016/j.ejvs.2021.12.024 PMID: 35027279
  3. Lattimer CR. CVD: A condition of underestimated severity. Int Angiol 2014; 33(3): 222-8. PMID: 24732585
  4. Rabe E, Guex JJ, Puskas A, Scuderi A, Fernandez Quesada F. Epidemiology of chronic venous disorders in geographically diverse populations: Results from the Vein Consult Program. Int Angiol 2012; 31(2): 105-15. PMID: 22466974
  5. Ortega MA, Fraile-Martínez O, García-Montero C, et al. Understanding chronic venous disease: A critical overview of its pathophysiology and medical management. J Clin Med 2021; 10(15): 3239. doi: 10.3390/jcm10153239 PMID: 34362022
  6. Evans CJ, Fowkes FG, Ruckley CV, Lee AJ. Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study. J Epidemiol Community Health 1999; 53(3): 149-53. doi: 10.1136/jech.53.3.149 PMID: 10396491
  7. Lee AJ, Robertson LA, Boghossian SM, et al. Progression of varicose veins and chronic venous insufficiency in the general population in the Edinburgh Vein Study. J Vasc Surg Venous Lymphat Disord 2015; 3(1): 18-26. doi: 10.1016/j.jvsv.2014.09.008 PMID: 26993676
  8. Bergan JJ, Schmid-Schönbein GW, Smith PDC, Nicolaides AN, Boisseau MR, Eklof B. Chronic venous disease. N Engl J Med 2006; 355(5): 488-98. doi: 10.1056/NEJMra055289 PMID: 16885552
  9. Santiago FR, Ulloa J, Régnier C, et al. The impact of lower limb chronic venous disease on quality of life: Patient and physician perspectives. J Comp Eff Res 2022; 11(11): 789-803. doi: 10.2217/cer-2022-0054 PMID: 35642553
  10. Brand FN, Dannenberg AL, Abbott RD, Kannel WB. The epidemiology of varicose veins: The Framingham Study. Am J Prev Med 1988; 4(2): 96-101. doi: 10.1016/S0749-3797(18)31203-0 PMID: 3395496
  11. Castro-Ferreira R, Cardoso R, Leite-Moreira A, Mansilha A. The role of endothelial dysfunction and inflammation in chronic venous disease. Ann Vasc Surg 2018; 46: 380-93. doi: 10.1016/j.avsg.2017.06.131 PMID: 28688874
  12. Labropoulos N. How does chronic venous disease progress from the first symptoms to the advanced stages? A review. Adv Ther 2019; 36(S1) (Suppl. 1): 13-9. doi: 10.1007/s12325-019-0885-3 PMID: 30758741
  13. Takase S, Bergan JJ, Schmid-Schönbein G. Expression of adhesion molecules and cytokines on saphenous veins in chronic venous insufficiency. Ann Vasc Surg 2000; 14(5): 427-35. doi: 10.1007/s100169910092 PMID: 10990550
  14. Takase S, Schmid-Schönbein G, Bergan JJ. Leukocyte activation in patients with venous insufficiency. J Vasc Surg 1999; 30(1): 148-56. doi: 10.1016/S0741-5214(99)70187-4 PMID: 10394165
  15. Saharay M, Shields DA, Georgiannos SN, Porter JB, Scurr JH, Coleridge Smith PD. Endothelial activation in patients with chronic venous disease. Eur J Vasc Endovasc Surg 1998; 15(4): 342-9. doi: 10.1016/S1078-5884(98)80039-7 PMID: 9610348
  16. Tisato V, Zauli G, Voltan R, et al. Endothelial cells obtained from patients affected by chronic venous disease exhibit a pro-inflammatory phenotype. PLoS One 2012; 7(6): e39543. doi: 10.1371/journal.pone.0039543 PMID: 22737245
  17. Saharay M, Shields DA, Porter JB, Scurr JH, Coleridge Smith PD. Leukocyte activity in the microcirculation of the leg in patients with chronic venous disease. J Vasc Surg 1997; 26(2): 265-73. doi: 10.1016/S0741-5214(97)70188-5 PMID: 9279314
  18. Serralheiro P, Soares A, Costa Almeida C, Verde I. TGF-β1 in vascular wall pathology: Unraveling chronic venous insufficiency pathophysiology. Int J Mol Sci 2017; 18(12): 2534. doi: 10.3390/ijms18122534 PMID: 29186866
  19. Komarów W, Hawro P, Lekston A, Urbanek T, Zagrodzki P. Endothelial dysfunction in patients with chronic venous disease: An evaluation based on the flow-mediated dilatation test. Int Angiol 2015; 34(1): 36-42. PMID: 25027597
  20. Matic P, Jolic S, Tanaskovic S, et al. Chronic venous disease and comorbidities. Angiology 2015; 66(6): 539-44. doi: 10.1177/0003319714541988 PMID: 25005764
  21. Nicolaides A, Kakkos S, Baekgaard N, et al. Management of chronic venous disorders of the lower limbs. Guidelines according to scientific evidence. Part I. Int Angiol 2018; 37(3): 181-254. doi: 10.23736/S0392-9590.18.03999-8 PMID: 29871479
  22. Bogachev VY, Boldin BV, Lobanov VN. Benefits of micronized purified flavonoid fraction as adjuvant therapy on inflammatory response after sclerotherapy. Int Angiol 2018; 37(1): 71-8. doi: 10.23736/S0392-9590.17.03868-8 PMID: 28945060
  23. Yiannakopoulou E. Safety concerns for sclerotherapy of telangiectases, reticular and varicose veins. Pharmacology 2016; 98(1-2): 62-9. doi: 10.1159/000445436 PMID: 27104778
  24. Ramelet AA, Boisseau MR, Allegra C, et al. 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 2005; 33(4): 309-19. PMID: 16317240
  25. Chen H, Shen Y, Zhang H, et al. Clinical application of polylactic acid/gelatin nanofibre membrane in hard-to-heal lower extremity venous ulcers. J Wound Care 2022; 31(11): 930-40. doi: 10.12968/jowc.2022.31.11.930 PMID: 36367804
  26. Gibello L, D’Antico S, Salafia M, et al. First pilot case-control interventional study using autologous extracellular vesicles to treat chronic venous ulcers unresponsive to conventional treatments. Pharmacol Res 2023; 190: 106718. doi: 10.1016/j.phrs.2023.106718 PMID: 36878306
  27. Nocera R, Eletto D, Santoro V, et al. 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. Plants 2023; 12(5): 1051. doi: 10.3390/plants12051051 PMID: 36903912
  28. Seo MG, Jo MJ, Hong NI, et al. Anti-inflammatory and anti-vascular leakage effects by combination of Centella asiatica and Vitis vinifera L. leaf extracts. Evid Based Complement Alternat Med 2021; 2021: 1-18. doi: 10.1155/2021/7381620 PMID: 33936244
  29. Benavente-García O, Castillo J. Update on uses and properties of Citrus flavonoids: New findings in anticancer, cardiovascular, and anti-inflammatory activity. J Agric Food Chem 2008; 56(15): 6185-205. doi: 10.1021/jf8006568 PMID: 18593176
  30. Ja M. Manthey JA, Guthrie N, Grohmann K. Biological properties of citrus flavonoids pertaining to cancer and inflammation. Curr Med Chem 2001; 8(2): 135-53.https://pubmed.ncbi.nlm.nih.gov/11172671/ Internet.
  31. Mahmoud AM, Hernández Bautista RJ, Sandhu MA, Hussein OE. Beneficial effects of Citrus flavonoids on cardiovascular and metabolic health. Oxid Med Cell Longev 2019; 2019: 1-19. doi: 10.1155/2019/5484138 PMID: 30962863
  32. Saini RK, Ranjit A, Sharma K, et al. Bioactive compounds of Citrus fruits: A review of composition and health benefits of carotenoids, flavonoids, limonoids, and terpenes. Antioxidants 2022; 11(2): 239. doi: 10.3390/antiox11020239 PMID: 35204122
  33. Zibaee E, Kamalian S, Tajvar M, et al. Citrus species: A review of traditional uses, phytochemistry and pharmacology. Curr Pharm Des 2020; 26(1): 44-97. doi: 10.2174/1381612825666191127115601 PMID: 31775593
  34. Duarte A, Fernandes J, Bernardes J, et al. Citrus as a component of the mediterranean diet. J Spatial Organ Dyn 2016; 4: 289-304.
  35. Flora e Funga do Brasil. Available from: https://floradobrasil.jbrj.gov.br (accessed on 7-7-2024)
  36. Chhikara N, Kour R, Jaglan S, Gupta P, Gat Y, Panghal A. Citrus medica: Nutritional, phytochemical composition and health benefits – A review. Food Funct 2018; 9(4): 1978-92. doi: 10.1039/C7FO02035J PMID: 29594287
  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. Khan UM, Sameen A, Aadil RM, et al. Citrus genus and its waste utilization: A review on health-promoting activities and industrial application. Evid Based Complement Alternat Med 2021; 2021: 1-17. doi: 10.1155/2021/2488804 PMID: 34795782
  42. Liu Y, Heying E, Tanumihardjo SA. History, global distribution, and nutritional importance of Citrus fruits. Compr Rev Food Sci Food Saf 2012; 11(6): 530-45. doi: 10.1111/j.1541-4337.2012.00201.x
  43. Chen R, Qi QL, Wang MT, Li QY. Therapeutic potential of naringin: An overview. Pharm Biol 2016; 54(12): 3203-10. doi: 10.1080/13880209.2016.1216131 PMID: 27564838
  44. Lu Y, Zhang C, Bucheli P, Wei D. Citrus flavonoids in fruit and traditional Chinese medicinal food ingredients in China. Plant Foods Hum Nutr 2006; 61(2): 55-63. doi: 10.1007/s11130-006-0014-8 PMID: 16816988
  45. Panche AN, Diwan AD, Chandra SR. Flavonoids: An overview. J Nutr Sci 2016; 5: e47. doi: 10.1017/jns.2016.41 PMID: 28620474
  46. Benavente-García O, Castillo J, Marin FR, Ortuño A, Del Río JA. Uses and properties of citrus flavonoids. J Agric Food Chem 1997; 45(12): 4505-15. doi: 10.1021/jf970373s PMID: 18593176
  47. Li C, Du G-H. Diosmin Natural small molecule drugs from plants. Singapore: Springer, Singapore 2018; pp. 65-9. doi: 10.1007/978-981-10-8022-7_10
  48. Nicolaides AN. The benefits of micronized purified flavonoid fraction (MPFF) throughout the progression of chronic venous disease. Adv Ther 2020; 37(S1) (Suppl. 1): 1-5. doi: 10.1007/s12325-019-01218-8 PMID: 31970659
  49. Victor MM, David JM, Cortez MVM, Leite JL, da Silva GSB. 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 2021; 12(1): 313-20. doi: 10.1007/s12649-020-00982-x
  50. Bogucka KA. Diosmin – isolation techniques, determination in plant material and pharmaceutical formulations, and clinical use. Nat Prod Commun 2013; 8: 1934578X1300800.
  51. Huwait E, Mobashir M. Potential and therapeutic roles of diosmin in human diseases. Biomedicines 2022; 10(5): 1076. doi: 10.3390/biomedicines10051076 PMID: 35625813
  52. Mustafa S, Akbar M, Khan MA, et al. Plant metabolite diosmin as the therapeutic agent in human diseases. Curr Res Pharmacol Drug Disc 2022; 3: 100122. doi: 10.1016/j.crphar.2022.100122 PMID: 36568270
  53. Imam F, Al-Harbi NO, Al-Harbi MM, et al. 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 2015; 102: 1-11. doi: 10.1016/j.phrs.2015.09.001 PMID: 26361726
  54. Feldo M, Wójciak-Kosior M, Sowa I, et al. Effect of diosmin administration in patients with chronic venous disorders on selected factors affecting angiogenesis. Molecules 2019; 24(18): 3316. doi: 10.3390/molecules24183316 PMID: 31547271
  55. Şimşek E, Koçak O, Yıldırım K, et al. The anti-angiogenic and anti-microbial effect of diosmin: Potential receptor interactions via molecular docking. Rev Bras Farmacogn 2023; 33(2): 422-31. doi: 10.1007/s43450-023-00365-y
  56. Shalkami AS, Hassan MIA, Bakr AG. Anti-inflammatory, antioxidant and anti-apoptotic activity of diosmin in acetic acid-induced ulcerative colitis. Hum Exp Toxicol 2018; 37(1): 78-86. doi: 10.1177/0960327117694075 PMID: 29187079
  57. Abdel-Rehe MA, Messiha BAS, Abo-Saif AA. Hepatoprotective effect of diosmin on iron-induced liver damage. Int J Pharmacol 2017; 13(6): 529-40. doi: 10.3923/ijp.2017.529.540
  58. Cypriani B, Limasset B, Carrié ML, et al. Antioxidant activity of micronized diosmin on oxygen species from stimulated human neutrophils. Biochem Pharmacol 1993; 45(7): 1531-5. doi: 10.1016/0006-2952(93)90056-3 PMID: 8385947
  59. Silambarasan T, Raja B. Diosmin, a bioflavonoid reverses alterations in blood pressure, nitric oxide, lipid peroxides and antioxidant status in DOCA-salt induced hypertensive rats. Eur J Pharmacol 2012; 679(1-3): 81-9. doi: 10.1016/j.ejphar.2011.12.040 PMID: 22266490
  60. Araujo D, Viana F, Osswald W. Diosmin therapy alters the metabolism of noradrenaline by the varicose human saphenous vein. Pharmacol Res 1991; 24(3): 253-6. doi: 10.1016/1043-6618(91)90088-F PMID: 1956869
  61. Refaat J, Yehia S, Ramadan A. Rhoifolin: A review of sources and biological activities. Int J Pharmacogn 2015; 2: 102-9.
  62. Eldahshan OA, Azab SS. Anti-inflammatory effect of apigenin-7- neohesperidoside (rhoifolin) in carrageenin-induced rat oedema model. JAPS 2012; 2(8): 74-9.
  63. Negm WA, El-Kadem AH, Elekhnawy E, et al. Wound-healing potential of rhoifolin-rich fraction isolated from Sanguisorba officinalis roots supported by enhancing re-epithelization, angiogenesis, anti-inflammatory, and antimicrobial effects. Pharmaceuticals 2022; 15(2): 178. doi: 10.3390/ph15020178 PMID: 35215291
  64. Peng S, Hu C, Liu X, et al. 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 2020; 53(6): e9489. doi: 10.1590/1414-431x20209489
  65. Rizza S, Muniyappa R, Iantorno M, et al. 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 2011; 96(5): E782-92. doi: 10.1210/jc.2010-2879 PMID: 21346065
  66. Karetová D, Suchopár J, Bultas J. Diosmin/hesperidin: A cooperating tandem, or is diosmin crucial and hesperidin an inactive ingredient only? Vnitr Lek 2020; 66(2): 97-103. doi: 10.36290/vnl.2020.016 PMID: 32942884
  67. Wilmsen PK, Spada DS, Salvador M. Antioxidant activity of the flavonoid hesperidin in chemical and biological systems. J Agric Food Chem 2005; 53(12): 4757-61. doi: 10.1021/jf0502000 PMID: 15941311
  68. Hirata A, Murakami Y, Shoji M, Kadoma Y, Fujisawa S. Kinetics of radical-scavenging activity of hesperetin and hesperidin and their inhibitory activity on COX-2 expression. Anticancer Res 2005; 25(5): 3367-74. PMID: 16101151
  69. Kim GD. Hesperidin inhibits vascular formation by blocking the AKT/mTOR signaling pathways. Prev Nutr Food Sci 2015; 20(4): 221-9. doi: 10.3746/pnf.2015.20.4.221 PMID: 26770908
  70. Habauzit V, Sacco SM, Gil-Izquierdo A, et al. Differential effects of two citrus flavanones on bone quality in senescent male rats in relation to their bioavailability and metabolism. Bone 2011; 49(5): 1108-16. doi: 10.1016/j.bone.2011.07.030 PMID: 21820093
  71. Cavia-Saiz M, Busto MD, Pilar-Izquierdo MC, Ortega N, Perez- Mateos M, Muñiz P. Antioxidant properties, radical scavenging activity and biomolecule protection capacity of flavonoid naringenin and its glycoside naringin: A comparative study. J Sci Food Agric 2010; 90(7): 1238-44. doi: 10.1002/jsfa.3959 PMID: 20394007
  72. Bacanlı M, Başaran AA, Başaran N. The antioxidant and antigenotoxic properties of citrus phenolics limonene and naringin. Food Chem Toxicol 2015; 81: 160-70. doi: 10.1016/j.fct.2015.04.015 PMID: 25896273
  73. Li Q, Wang Y, Zhang L, et al. Naringenin exerts anti-angiogenic effects in human endothelial cells: Involvement of ERRα/VEGF/KDR signaling pathway. Fitoterapia 2016; 111: 78-86. doi: 10.1016/j.fitote.2016.04.015 PMID: 27105956
  74. Rustam M, Ifora I, Fauziah F. Potential anti-inflammatory effects of eriocitrin: A review. J Drug Deliv Ther 2022; 12(3): 187-92. doi: 10.22270/jddt.v12i3.5456
  75. Xu J, Ma L, Fu P. 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 2021; 9(4): 350-0. doi: 10.21037/atm-21-337 PMID: 33708977
  76. Liu J, Huang H, Huang Z, et al. Eriocitrin in combination with resveratrol ameliorates LPS-induced inflammation in RAW264.7 cells and relieves TPA-induced mouse ear edema. J Funct Foods 2019; 56: 321-32. doi: 10.1016/j.jff.2019.03.008
  77. Guo G, Shi W, Shi F, et al. Anti-inflammatory effects of eriocitrin against the dextran sulfate sodium–induced experimental colitis in murine model. J Biochem Mol Toxicol 2019; 33(11): e22400. doi: 10.1002/jbt.22400 PMID: 31593355
  78. He J, Zhou D, Yan B. 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 2020; 8(12): 757. doi: 10.21037/atm-20-4258
  79. Denaro M, Smeriglio A, Trombetta D. Antioxidant and anti-inflammatory activity of citrus flavanones mix and its stability after in vitro simulated digestion. Antioxidants 2021; 10(2): 140. doi: 10.3390/antiox10020140 PMID: 33498195
  80. Yao L, Liu W, Bashir M, Nisar MF, Wan CC. Eriocitrin: A review of pharmacological effects. Biomed Pharmacother 2022; 154: 113563. doi: 10.1016/j.biopha.2022.113563 PMID: 35987162
  81. Takase T, Ikeuchi S, Inoue T, Mukai R. 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 2021; 84(7): 2048-52. doi: 10.1021/acs.jnatprod.1c00271 PMID: 34189920
  82. Miyake Y, Shimoi K, Kumazawa S, Yamamoto K, Kinae N, Osawa T. Identification and antioxidant activity of flavonoid metabolites in plasma and urine of eriocitrin-treated rats. J Agric Food Chem 2000; 48(8): 3217-24. doi: 10.1021/jf990994g PMID: 10956094
  83. Comalada M, Camuesco D, Sierra S, et al. In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-κB pathway. Eur J Immunol 2005; 35(2): 584-92. doi: 10.1002/eji.200425778 PMID: 15668926
  84. Boots AW, Wilms LC, Swennen ELR, Kleinjans JCS, Bast A, Haenen GRMM. In vitro and ex vivo anti-inflammatory activity of quercetin in healthy volunteers. Nutrition 2008; 24(7-8): 703-10. doi: 10.1016/j.nut.2008.03.023 PMID: 18549926
  85. Kleemann R, Verschuren L, Morrison M, et al. Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Atherosclerosis 2011; 218(1): 44-52. doi: 10.1016/j.atherosclerosis.2011.04.023 PMID: 21601209
  86. Hollman PCH, van Trijp JMP, Mengelers MJB, de Vries JHM, Katan MB. Bioavailability of the dietary antioxidant flavonol quercetin in man. Cancer Lett 1997; 114(1-2): 139-40. doi: 10.1016/S0304-3835(97)04644-2 PMID: 9103273
  87. Baghel S, Shrivastava N, Baghel P, et al. A review of quercetin: Antioxidant and anticancer properties. World J Pharm Pharm Sci 2012; 1: 146-60.
  88. Sakanashi Y, Oyama K, Matsui H, et al. Possible use of quercetin, an antioxidant, for protection of cells suffering from overload of intracellular Ca2+: A model experiment. Life Sci 2008; 83(5-6): 164-9. doi: 10.1016/j.lfs.2008.05.009 PMID: 18586279
  89. Boots AW, Haenen GRMM, Bast A. Health effects of quercetin: From antioxidant to nutraceutical. Eur J Pharmacol 2008; 585(2-3): 325-37. doi: 10.1016/j.ejphar.2008.03.008 PMID: 18417116
  90. Tan W, Lin L, Li M, et al. Quercetin, a dietary-derived flavonoid, possesses antiangiogenic potential. Eur J Pharmacol 2003; 459(2-3): 255-62. doi: 10.1016/S0014-2999(02)02848-0 PMID: 12524154
  91. Igura K, Ohta T, Kuroda Y, Kaji K. Resveratrol and quercetin inhibit angiogenesis in vitro. Cancer Lett 2001; 171(1): 11-6. doi: 10.1016/S0304-3835(01)00443-8 PMID: 11485823
  92. Yoo H, Ku SK, Baek YD, Bae JS. Anti-inflammatory effects of rutin on HMGB1-induced inflammatory responses in vitro and in vivo. Inflamm Res 2014; 63(3): 197-206. doi: 10.1007/s00011-013-0689-x PMID: 24292859
  93. Yang J, Guo J, Yuan J. In vitro antioxidant properties of rutin. Lebensm Wiss Technol 2008; 41(6): 1060-6. doi: 10.1016/j.lwt.2007.06.010
  94. Choi SS, Park HR, Lee KA. A comparative study of rutin and rutin glycoside: Antioxidant activity, anti-inflammatory effect, effect on platelet aggregation and blood coagulation. Antioxidants 2021; 10(11): 1696. doi: 10.3390/antiox10111696 PMID: 34829567
  95. Matsubara K, Ishihara K, Mizushina Y, Mori M, Nakajima N. Anti-angiogenic activity of quercetin and its derivatives. Lett Drug Des Discov 2004; 1(4): 329-33. doi: 10.2174/1570180043398533
  96. Ziberna L, Tramer F, Moze S, Vrhovsek U, Mattivi F, Passamonti S. Transport and bioactivity of cyanidin 3-glucoside into the vascular endothelium. Free Radic Biol Med 2012; 52(9): 1750-9. doi: 10.1016/j.freeradbiomed.2012.02.027 PMID: 22387282
  97. Xu JW, Ikeda K, Yamori Y. Upregulation of endothelial nitric oxide synthase by cyanidin-3-glucoside, a typical anthocyanin pigment. Hypertension 2004; 44(2): 217-22. doi: 10.1161/01.HYP.0000135868.38343.c6 PMID: 15226277
  98. Trinei M, Carpi A, Menabo’ R, et al. Dietary intake of cyanidin-3-glucoside induces a long-lasting cardioprotection from ischemia/reperfusion injury by altering the microbiota. J Nutr Biochem 2022; 101: 108921. doi: 10.1016/j.jnutbio.2021.108921 PMID: 34864150
  99. Amin H. 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.
  100. Wang H, Nair MG, Strasburg GM, et al. Antioxidant and antiinflammatory activities of anthocyanins and their aglycon, cyanidin, from tart cherries. J Nat Prod 1999; 62(2): 294-6. doi: 10.1021/np980501m PMID: 10075763
  101. Zhang Y, Wang X, Wang Y, Liu Y, Xia M. Supplementation of cyanidin-3-O-β-glucoside promotes endothelial repair and prevents enhanced atherogenesis in diabetic apolipoprotein E-deficient mice. J Nutr 2013; 143(8): 1248-53. doi: 10.3945/jn.113.177451 PMID: 23761653
  102. Eddin LB, Jha NK, Meeran MFN, Kesari KK, Beiram R, Ojha S. Neuroprotective potential of limonene and limonene containing natural products. Molecules 2021; 26(15): 4535. doi: 10.3390/molecules26154535 PMID: 34361686
  103. 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. Sun J. D-Limonene: Safety and clinical applications. Altern Med Rev 2007; 12(3): 259-64. PMID: 18072821
  105. Hirota R, Roger NN, Nakamura H, Song HS, Sawamura M, Suganuma N. Anti-inflammatory effects of limonene from Yuzu (Citrus junos Tanaka) essential oil on eosinophils. J Food Sci 2010; 75(3): H87-92. doi: 10.1111/j.1750-3841.2010.01541.x PMID: 20492298
  106. Yu L, Yan J, Sun Z. 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 2017; 15(4): 2339-46. doi: 10.3892/mmr.2017.6241 PMID: 28260017
  107. AlSaffar RM, Rashid S, Ahmad SB, et al. D-limonene (5 (one-methyl-four-1-methylethenyl) cyclohexane) diminishes CCl4-induced cardiac toxicity by alleviating oxidative stress, inflammatory and cardiac markers. Redox Rep 2022; 27(1): 92-9. doi: 10.1080/13510002.2022.2062947 PMID: 35435141
  108. Chidambara Murthy KN, Jayaprakasha GK, Patil BS. D-limonene rich volatile oil from blood oranges inhibits angiogenesis, metastasis and cell death in human colon cancer cells. Life Sci 2012; 91(11-12): 429-39. doi: 10.1016/j.lfs.2012.08.016 PMID: 22935404
  109. Bungau SG, Vesa CM, Bustea C, et al. Antioxidant and hypoglycemic potential of essential oils in diabetes mellitus and its complications. Int J Mol Sci 2023; 24(22): 16501. doi: 10.3390/ijms242216501 PMID: 38003691
  110. Foti MC, Ingold KU. Mechanism of inhibition of lipid peroxidation by gamma-terpinene, an unusual and potentially useful hydrocarbon antioxidant. J Agric Food Chem 2003; 51(9): 2758-65. doi: 10.1021/jf020993f PMID: 12696969
  111. Guo Y, Baschieri A, Amorati R, Valgimigli L. Synergic antioxidant activity of γ-terpinene with phenols and polyphenols enabled by hydroperoxyl radicals. Food Chem 2021; 345: 128468. doi: 10.1016/j.foodchem.2020.128468 PMID: 33341300
  112. Ramalho T, Pacheco de Oliveira M, Lima A, Bezerra-Santos C, Piuvezam M. Gamma-terpinene modulates acute inflammatory response in mice. Planta Med 2015; 81(14): 1248-54. doi: 10.1055/s-0035-1546169 PMID: 26132854
  113. Ramalho T, Filgueiras L, Pacheco de Oliveira M, et al. Gamma-terpinene modulation of lps-stimulated macrophages is dependent on the PGE2/IL-10 axis. Planta Med 2016; 82(15): 1341-5. doi: 10.1055/s-0042-107799 PMID: 27224271
  114. Asikin Y, Shimizu K, Iwasaki H, Oku H, Wada K. Stress amelioration and anti-inflammatory potential of Shiikuwasha (Citrus depressa Hayata) essential oil, limonene, and γ-terpinene. Yao Wu Shi Pin Fen Xi 2022; 30(3): 454-65. doi: 10.38212/2224-6614.3414
  115. Carnesecchi S, Bras-Gonçalves R, Bradaia A, et al. Geraniol, a component of plant essential oils, modulates DNA synthesis and potentiates 5-fluorouracil efficacy on human colon tumor xenografts. Cancer Lett 2004; 215(1): 53-9. doi: 10.1016/j.canlet.2004.06.019 PMID: 15374632
  116. de Carvalho KIM, Bonamin F, dos Santos RC, et al. Geraniol-a flavoring agent with multifunctional effects in protecting the gastric and duodenal mucosa. Naunyn Schmiedebergs Arch Pharmacol 2014; 387(4): 355-65. doi: 10.1007/s00210-013-0947-z PMID: 24337826
  117. Solórzano-Santos F, Miranda-Novales MG. Essential oils from aromatic herbs as antimicrobial agents. Curr Opin Biotechnol 2012; 23(2): 136-41. doi: 10.1016/j.copbio.2011.08.005 PMID: 21903378
  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. Ammar RB, Mohamed ME, Alfwuaires M, et al. 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. Nutrients 2022; 14(22): 4817. doi: 10.3390/nu14224817 PMID: 36432506
  120. El-Bassossy HM, Elberry AA, Ghareib SA. Geraniol improves the impaired vascular reactivity in diabetes and metabolic syndrome through calcium channel blocking effect. J Diabetes Complicat 2016; 30(6): 1008-16. doi: 10.1016/j.jdiacomp.2016.04.006 PMID: 27131411
  121. Prasad SN, Muralidhara M. Analysis of the antioxidant activity of geraniol employing various in-vitro models: Relevance to neurodegeneration in diabetic neuropathy. Asian J Pharm Clin Res 2017; 10(7): 101. doi: 10.22159/ajpcr.2017.v10i7.18564
  122. Wittig C, Scheuer C, Parakenings J, Menger MD, Laschke MW. Geraniol suppresses angiogenesis by downregulating vascular endothelial growth factor (vegf)/vegfr-2 signaling. PLoS One 2015; 10(7): e0131946. doi: 10.1371/journal.pone.0131946 PMID: 26154255
  123. Roy A, Saraf S. Limonoids: Overview of significant bioactive triterpenes distributed in plants kingdom. Biol Pharm Bull 2006; 29(2): 191-201. doi: 10.1248/bpb.29.191 PMID: 16462017
  124. Mahmoud MF, Gamal S, El-Fayoumi HM. Limonin attenuates hepatocellular injury following liver ischemia and reperfusion in rats via toll-like receptor dependent pathway. Eur J Pharmacol 2014; 740: 676-82. doi: 10.1016/j.ejphar.2014.06.010 PMID: 24967531
  125. Chen J, Liu BX, Shen Q, et al. Limonin inhibits angiogenesis and metastasis of human breast cancer cells by suppressing the VEGFR2/IGFR1-mediated STAT3 signaling pathway. Transl Cancer Res 2020; 9(11): 6820-32. doi: 10.21037/tcr-20-1992 PMID: 35117291
  126. Chen SX, Xiang JY, Han JX, et al. Essential oils from spices inhibit cholinesterase activity and improve behavioral disorder in AlCl3 induced dementia. Chem Biodivers 2022; 19(1): e202100443. doi: 10.1002/cbdv.202100443 PMID: 34855291
  127. Borges RM, de Assis Ferreira G, Campos MM, Teixeira AM, das Neves Costa F, Chagas FO. Data base similarity (DBsimilarity) of natural products to aid compound identification on MS and NMR pipelines, similarity networking, and more. Phytochem Anal 2024; 35(1): 93-101. doi: 10.1002/pca.3277 PMID: 37592443
  128. Li J, Zhao R, Miao P, et al. Discovery of anti-inflammatory natural flavonoids: Diverse scaffolds and promising leads for drug discovery. Eur J Med Chem 2023; 260: 115791. doi: 10.1016/j.ejmech.2023.115791 PMID: 37683361
  129. Rakha A, Umar N, Rabail R, et al. Anti-inflammatory and anti-allergic potential of dietary flavonoids: A review. Biomed Pharmacother 2022; 156: 113945. doi: 10.1016/j.biopha.2022.113945 PMID: 36411631
  130. Verri WA, Vicentini FTMC, Baracat MM. Flavonoids as anti-inflammatory and analgesic drugs: Mechanisms of action and perspectives in the development of pharmaceutical forms. Studies in Natural Products Chemistry. Elsevier 2012.
  131. Nones J, e Spohr TCLS, Gomes FCA. Hesperidin, a flavone glycoside, as mediator of neuronal survival. Neurochem Res 2011; 36(10): 1776-84. doi: 10.1007/s11064-011-0493-3 PMID: 21553255
  132. Rufino AT, Ribeiro M, Sousa C, et al. 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 2015; 750: 141-50. doi: 10.1016/j.ejphar.2015.01.018 PMID: 25622554
  133. d’Alessio PA, Ostan R, Bisson JF, Schulzke JD, Ursini MV, Béné MC. Oral administration of d-Limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans. Life Sci 2013; 92(24-26): 1151-6. doi: 10.1016/j.lfs.2013.04.013 PMID: 23665426
  134. Nishida S, Satoh H. Comparative vasodilating actions among terpenoids and flavonoids contained in Ginkgo biloba extract. Clin Chim Acta 2004; 339(1-2): 129-33. doi: 10.1016/j.cccn.2003.10.004 PMID: 14687903
  135. Su Z, Wang C, Chang D, Zhu X, Sai C, Pei J. Limonin attenuates the stemness of breast cancer cells via suppressing MIR216A methylation. Biomed Pharmacother 2019; 112: 108699. doi: 10.1016/j.biopha.2019.108699 PMID: 30970511
  136. Quiroga PR, Nepote V, Baumgartner MT. Contribution of organic acids to α-terpinene antioxidant activity. Food Chem 2019; 277: 267-72. doi: 10.1016/j.foodchem.2018.10.100 PMID: 30502144
  137. Huang J, Fang Z, Bai C, et al. Novel nano-encapsulated limonene: Utilization of drug-in-cyclodextrin-in-liposome formulation to improve the stability and enhance the antioxidant activity. Int J Pharm 2024; 653: 123914. doi: 10.1016/j.ijpharm.2024.123914 PMID: 38373597
  138. Vieira AJ, Beserra FP, Souza MC, Totti BM, Rozza AL. Limonene: Aroma of innovation in health and disease. Chem Biol Interact 2018; 283: 97-106. doi: 10.1016/j.cbi.2018.02.007 PMID: 29427589
  139. Moriwaki M, Kito K, Nakagawa R, et al. Increased bioavailability of diosmetin-7-glucoside-γ-cyclodextrin inclusion complex compared with diosmin in Sprague-Dawley rats. Biosci Biotechnol Biochem 2023; 87(7): 771-6. doi: 10.1093/bbb/zbad051 PMID: 37133406
  140. Kanaze FI, Kokkalou E, Georgarakis M, Niopas I. 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 2004; 801(2): 363-7. doi: 10.1016/j.jchromb.2003.11.030 PMID: 14751808
  141. Barfi B, Asghari A, Rajabi M, Barfi A, Saeidi I. 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 A 2013; 1311: 30-40. doi: 10.1016/j.chroma.2013.08.078 PMID: 24011420

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers