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Quercetin as a Complementary Therapy in Substance Use Disorder: A Narrative Review

Document Type : Review Article

Authors

1 Institute of Neuropharmacology, Kerman Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran

2 Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran

Abstract

Substance use disorder (SUD) is a pervasive public health concern characterized by compulsive drug use despite adverse consequences. SUD treatment strategies aim to assist addicts in ending their obsessive drug-seeking and consumption. These approaches could be provided in a variety of venues utilizing a range of behavioral and pharmacological techniques. Emerging research explores alternative treatments for SUD, including medicinal plants. Quercetin, a natural flavonoid present in various fruits and vegetables, exhibits promising pharmacological properties. This naturally occurring pharmaceutical component has shown promise as a preventative measure against a wide range of disorders. It shields against neurodegeneration, oxidative stress, and inflammation, offering hope for central nervous system-related disorders. In terms of substance abuse, quercetin shows substantial promise. It demonstrates the ability to mitigate the adverse effects of substances, including methamphetamine, nicotine, morphine, heroin, and alcohol, through various mechanisms, including antioxidant, anti-inflammatory, and neuroprotective pathways. This review synthesizes recent evidence supporting quercetin as a complementary approach to conventional addiction treatments.

Keywords

Main Subjects

References
  1. Gardner EL. Addiction and brain reward and antireward pathways. Adv Psychosom Med. 2011;30:22-60. doi: 10.1159/000324065.
  2. Zhao Y, Sallie SN, Cui H, Zeng N, Du J, Yuan T, et al. Anterior cingulate cortex in addiction: new insights for neuromodulation. Neuromodulation. 2021;24(2):187-96. doi: 10.1111/ner.13291.
  3. Volkow ND, Morales M. The brain on drugs: from reward to addiction. Cell. 2015;162(4):712-25. doi: 10.1016/j. cell.2015.07.046.
  4. Volkow ND. Principles of Drug Addiction Treatment: A Research-Based Guide. 3rd ed. National Institute on Drug Abuse; 2018. p. 1-67.
  5. Mendes FR, da Rocha Prado D. Use of herbal medicine to treat drug addiction. In: Andrade AL, De Micheli D, eds. Innovations in the Treatment of Substance Addiction. Cham: Springer; 2016. p. 51-68. doi: 10.1007/978-3-319-43172-7_4.
  6. Lakhanpal P, Rai DK. Quercetin: a versatile flavonoid. Internet Journal of Medical Update. 2007;2(2):22-37.
  7. Anand David AV, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: a bioactive flavonoid. Pharmacogn Rev. 2016;10(20):84-9. doi: 10.4103/0973- 7847.194044.
  8. Ay M, Charli A, Jin H, Anantharam V, Kanthasamy A, Kanthasamy AG. Quercetin. In: Gupta RC, Lall R, Srivastava A, eds. Nutraceuticals. 2nd ed. Academic Press; 2021. p. 749- 55. doi: 10.1016/b978-0-12-821038-3.00043-4.
  9. Hou DD, Zhang W, Gao YL, Sun YZ, Wang HX, Qi RQ, et al. Anti-inflammatory effects of quercetin in a mouse model of MC903-induced atopic dermatitis. Int Immunopharmacol. 2019;74:105676. doi: 10.1016/j.intimp.2019.105676.
  10. Park EJ, Kim JY, Jeong MS, Park KY, Park KH, Lee MW, et al. Effect of topical application of quercetin-3-O-(2″-gallate)- α-L-rhamnopyranoside on atopic dermatitis in NC/Nga mice. J Dermatol Sci. 2015;77(3):166-72. doi: 10.1016/j. jdermsci.2014.12.005.
  11. Fuentes J, de Camargo AC, Atala E, Gotteland M, Olea-Azar C, Speisky H. Quercetin oxidation metabolite present in onion peel protects Caco-2 cells against the oxidative stress, NF-kB activation, and loss of epithelial barrier function induced by NSAIDs. J Agric Food Chem. 2021;69(7):2157-67. doi: 10.1021/acs.jafc.0c07085.
  12. Derosa G, Maffioli P, D’Angelo A, Di Pierro F. A role for quercetin in coronavirus disease 2019 (COVID-19). Phytother Res. 2021;35(3):1230-6. doi: 10.1002/ptr.6887.
  13. Nguyen TL, Bhattacharya D. Antimicrobial activity of quercetin: an approach to its mechanistic principle. Molecules. 2022;27(8):2494. doi: 10.3390/molecules27082494.
  14. Samini M. Quercetin effects on respiratory diseases. Res J Pharm Technol. 2020;13(4):2019-23. doi: 10.5958/0974- 360x.2020.00363.7.
  15. Asgharian P, Pirpour Tazekand A, Hosseini K, Forouhandeh H, Ghasemnejad T, Ranjbar M, et al. Potential mechanisms of quercetin in cancer prevention: focus on cellular and molecular targets. Cancer Cell Int. 2022;22(1):257. doi: 10.1186/s12935-022-02677-w.
  16. Rauf A, Imran M, Khan IA, Ur-Rehman M, Gilani SA, Mehmood Z, et al. Anticancer potential of quercetin: a comprehensive review. Phytother Res. 2018;32(11):2109-30. doi: 10.1002/ ptr.6155.
  17. Sharifi-Rad J, Quispe C, Shaheen S, El Haouari M, Azzini E, Butnariu M, et al. Flavonoids as potential anti-platelet aggregation agents: from biochemistry to health promoting abilities. Crit Rev Food Sci Nutr. 2022;62(29):8045-58. doi: 10.1080/10408398.2021.1924612.
  18. Zhurakulov SN, Narbutaeva DA, Karakulova AM, Tursunkhodzhaeva FM, Vinogradova VI. Aminomethylation of quercetin by tetrahydroisoquinoline derivatives and their biological activity. Chem Nat Compd. 2023;59(4):655-61. doi: 10.1007/s10600-023-04080-x.
  19. Sun GY, Li R, Yang B, Fritsche KL, Beversdorf DQ, Lubahn DB, et al. Quercetin potentiates docosahexaenoic acid to suppress lipopolysaccharide-induced oxidative/inflammatory responses, alter lipid peroxidation products, and enhance the adaptive stress pathways in BV-2 microglial cells. Int J Mol Sci. 2019;20(4):932. doi: 10.3390/ijms20040932.
  20. Ho CL, Kao NJ, Lin CI, Cross TL, Lin SH. Quercetin increases mitochondrial biogenesis and reduces free radicals in neuronal SH-SY5Y cells. Nutrients. 2022;14(16):3310. doi: 10.3390/nu14163310.
  21. Ugwu PI, Ben-Azu B, Ugwu SU, Uruaka CI, Nworgu CC, Okorie PO, et al. Preventive putative mechanisms involved in the psychopathologies of mice passively coping with psychosocial defeat stress by quercetin. Brain Res Bull. 2022;183:127-41. doi: 10.1016/j.brainresbull.2022.03.004.
  22. Grosso C, Santos M, Barroso MF. From plants to psycho-neurology: unravelling the therapeutic benefits of bioactive compounds in brain disorders. Antioxidants (Basel). 2023;12(8):1603. doi: 10.3390/antiox12081603.

23.Salehi B, Prakash Mishra A, Nigam M, Karazhan N, Shukla I, Kiełtyka-Dadasiewicz A, et al. Ficus plants: state of the art  from a phytochemical, pharmacological, and toxicological perspective. Phytother Res. 2021;35(3):1187-217. doi: 10.1002/ptr.6884.

  1. DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener. 2019;14(1):32. doi: 10.1186/s13024-019-0333-5.
  2. Kommaddi RP, Das D, Karunakaran S, Nanguneri S, Bapat D, Ray A, et al. Aβ mediates F-actin disassembly in dendritic spines leading to cognitive deficits in Alzheimer’s disease. J Neurosci. 2018;38(5):1085-99. doi: 10.1523/jneurosci.2127-17.2017.
  3. Weller J, Budson A. Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Res. 2018;7:F1000 Faculty Rev-1161. doi: 10.12688/f1000research.14506.1.
  4. Abolhasani F, Pourshojaei Y, Mohammadi F, Esmaeilpour K, Asadipour A, Ilaghi M, et al. Exploring the potential of a novel phenoxyethyl piperidine derivative with cholinesterase inhibitory properties as a treatment for dementia: insights from STZ animal model of dementia. Neurosci Lett. 2023;810:137332. doi: 10.1016/j.neulet.2023.137332.
  5. Joshi A, Vats N, Singh H, Kaushik V. Quercetin compound analysis to develop treatment for dementia associated with Alzheimer? s disease in humans: in-silico study. J Drug Alcohol Res. 2022;11(4):236174. doi: 10.4303/jdar/236174.
  6. Khan H, Ullah H, Aschner M, Cheang WS, Akkol EK. Neuroprotective effects of quercetin in Alzheimer’s disease. Biomolecules. 2019;10(1):59. doi: 10.3390/biom10010059.
  7. Paula PC, Angelica Maria SG, Luis CH, Gloria Patricia CG. Preventive effect of quercetin in a triple transgenic Alzheimer’s disease mice model. Molecules. 2019;24(12):2287. doi: 10.3390/molecules24122287.
  8. Balestrino R, Schapira AH. Parkinson disease. Eur J Neurol. 2020;27(1):27-42. doi: 10.1111/ene.14108.
  9. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science. 1997;276(5321):2045-7. doi: 10.1126/ science.276.5321.2045.
  10. Tamtaji OR, Hadinezhad T, Fallah M, Rezaei Shahmirzadi A, Taghizadeh M, Behnam M, et al. The therapeutic potential of quercetin in Parkinson’s disease: insights into its molecular and cellular regulation. Curr Drug Targets. 2020;21(5):509-18. doi: 10.2174/1389450120666191112155654.
  11. Sriraksa N, Wattanathorn J, Muchimapura S, Tiamkao S, Brown K, Chaisiwamongkol K. Cognitive-enhancing effect of quercetin in a rat model of Parkinson’s disease induced by 6-hydroxydopamine. Evid Based Complement Alternat Med. 2012;2012:823206. doi: 10.1155/2012/823206.
  12. Duc Nguyen H. Neurotherapeutic effects of quercetin and its metabolite compounds on cognitive impairment and Parkinson’s disease: an in-silico study. Eur J Drug Metab Pharmacokinet. 2023;48(2):151-69. doi: 10.1007/s13318- 023-00816-w.
  13. Chwastiak LA, Von Korff M. Disability in depression and back pain: evaluation of the World Health Organization Disability Assessment Schedule (WHO DAS II) in a primary care setting. J Clin Epidemiol. 2003;56(6):507-14. doi: 10.1016/s0895- 4356(03)00051-9.
  14. Xu D, Hu MJ, Wang YQ, Cui YL. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules. 2019;24(6):1123. doi: 10.3390/ molecules24061123.
  15. Holzmann I, da Silva LM, Corrêa da Silva JA, Steimbach VM, de Souza MM. Antidepressant-like effect of quercetin in bulbectomized mice and involvement of the antioxidant defenses, and the glutamatergic and oxidonitrergic pathways. Pharmacol Biochem Behav. 2015;136:55-63. doi: 10.1016/j. pbb.2015.07.003.
  16. Kosari-Nasab M, Shokouhi G, Ghorbanihaghjo A, Mesgari- Abbasi M, Salari AA. Quercetin mitigates anxiety-like behavior and normalizes hypothalamus-pituitary-adrenal axis function in a mouse model of mild traumatic brain injury. Behav Pharmacol. 2019;30(2-3):282-9. doi: 10.1097/ fbp.0000000000000480.
  17. Filošević Vujnović A, Jović K, Pištan E, Andretić Waldowski R. Influence of dopamine on fluorescent advanced glycation end products formation using Drosophila melanogaster. Biomolecules. 2021;11(3):453. doi: 10.3390/biom11030453.
  18. Chen F, Sun J, Zhang Y, Dai Y, Zhang Z, Chen C, et al. Quercetin ameliorates mitochondrial dysfunction and mitigates methamphetamine-induced anxiety-like behavior. bioRxiv [Preprint]. June 30, 2021. Available from: https:// www.biorxiv.org/content/10.1101/2021.06.29.450268v1.
  19. Rahmadi M, Suasana D, Lailis SR, Ratri DM, Ardianto C. The effects of quercetin on nicotine-induced reward effects in mice. J Basic Clin Physiol Pharmacol. 2021;32(4):327-33. doi: 10.1515/jbcpp-2020-0418.
  20. Al Anany MG, Kamal AM, El Saied K. Effects of curcumin and/ or quercetin on nicotine-induced lung and liver toxicity in adult male albino rat. Al-Azhar Assiut Med J. 2015;13(2):93-102.
  21. Habibi Asl B, Delazar A, Assady M. Effects of quercetin and ACTH on morphine-induced tolerance and dependence in mice: attenuation of morphine tolerance by quercetin. Iran J Pharm Sci. 2006;2(3):137-42. doi: 10.22037/ijps.v2.39736.
  22. Singh A, Naidu PS, Kulkarni SK. Quercetin, a bioflavonoid, reverses development of tolerance and dependence to morphine. Drug Dev Res. 2002;57(4):167-72. doi: 10.1002/ ddr.10119.
  23. ElShebiney S, Elgohary R, El-Shamarka M, Mowaad N, Abulseoud OA. Natural polyphenols-resveratrol, quercetin, magnolol, and β-catechin-block certain aspects of heroin addiction and modulate striatal IL-6 and TNF-α. Toxics. 2023;11(4):379. doi: 10.3390/toxics11040379.
  24. Xu B, Wang Z, Li G, Li B, Lin H, Zheng R, et al. Heroin-administered mice involved in oxidative stress and exogenous antioxidant-alleviated withdrawal syndrome. Basic Clin Pharmacol Toxicol. 2006;99(2):153-61. doi: 10.1111/j.1742- 7843.2006.pto_461.x.
  25. Raygude KS, Kandhare AD, Ghosh P, Ghule AE, Bodhankar SL. Evaluation of ameliorative effect of quercetin in experimental model of alcoholic neuropathy in rats. Inflammopharmacology. 2012;20(6):331-41. doi: 10.1007/s10787-012-0122-z.
  26. Kahraman A, Çakar H, Köken T. The protective effect of quercetin on long-term alcohol consumption-induced oxidative stress. Mol Biol Rep. 2012;39(3):2789-94. doi: 10.1007/s11033-011-1037-2.
  27. Singh A, Naidu PS, Kulkarni SK. Reversal of aging and chronic ethanol-induced cognitive dysfunction by quercetin a bioflavonoid. Free Radic Res. 2003;37(11):1245-52. doi: 10.1080/10715760310001616014.
  28. Joshi D, Naidu PS, Singh A, Kulkarni SK. Protective effect of quercetin on alcohol abstinence-induced anxiety and convulsions. J Med Food. 2005;8(3):392-6. doi: 10.1089/ jmf.2005.8.392.
  29. Yunusoğlu O. Evaluation of the effects of quercetin on the rewarding property of ethanol in mice. Neurosci Lett. 2022;768:136383. doi: 10.1016/j.neulet.2021.136383.
  30. Sibanda NC, Kornhaber R, Hunt GE, Morley K, Cleary M. Prevalence and risk factors of emergency department presentations with methamphetamine intoxication or dependence: a systematic review and meta-analysis. Issues Ment Health Nurs. 2019;40(7):567-78. doi: 10.1080/01612840.2018.1553003.
  31. Darke S, Kaye S, Duflou J. Rates, characteristics and circumstances of methamphetamine-related death in Australia: a national 7-year study. Addiction. 2017;112(12):2191-201. doi: 10.1111/add.13897.
  32. Cadet JL, Jayanthi S, Deng X. Methamphetamine-induced neuronal apoptosis involves the activation of multiple death pathways. Review. Neurotox Res. 2005;8(3-4):199-206. doi: 10.1007/bf03033973.
  33. Itzhak Y, Achat-Mendes C. Methamphetamine and MDMA (ecstasy) neurotoxicity: ‘of mice and men’. IUBMB Life. 2004;56(5):249-55. doi: 10.1080/15216540410001727699.
  34. Takebayashi K, Sekine Y, Takei N, Minabe Y, Isoda H, Takeda H, et al. Metabolite alterations in basal ganglia associated with psychiatric symptoms of abstinent toluene users: a proton MRS study. Neuropsychopharmacology. 2004;29(5):1019-26. doi: 10.1038/sj.npp.1300426.
  35. Volkow ND, Chang L, Wang GJ, Fowler JS, Franceschi D, Sedler M, et al. Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. J Neurosci. 2001;21(23):9414-8. doi: 10.1523/ jneurosci.21-23-09414.2001.
  36. Volkow ND, Chang L, Wang GJ, Fowler JS, Leonido-Yee M, Franceschi D, et al. Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am J Psychiatry. 2001;158(3):377-82. doi: 10.1176/ appi.ajp.158.3.377.
  37. Petit A, Karila L, Chalmin F, Lejoyeux M. Methamphetamine addiction: a review of the literature. J Addict Res Ther. 2012;S1:1-6. doi: 10.4172/2155-6105.s1-006.
  38. Swan GE, Lessov-Schlaggar CN. The effects of tobacco smoke and nicotine on cognition and the brain. Neuropsychol Rev. 2007;17(3):259-73. doi: 10.1007/s11065-007-9035-9.
  39. Warnakulasuriya SN, Ziaullah, Rupasinghe HP. Novel long chain fatty acid derivatives of quercetin-3-O-glucoside reduce cytotoxicity induced by cigarette smoke toxicants in human fetal lung fibroblasts. Eur J Pharmacol. 2016;781:128-38. doi: 10.1016/j.ejphar.2016.04.011.
  40. Elsyade R, Khaled D. The possible protective role of quercetin on nicotine induced liver and kidney damage of neonates albino rats: histological and immunohistochemical study. Egypt J Histol. 2023;46(2):495-505. doi: 10.21608/ ejh.2021.106065.1588.
  41. Ola D, Adeyemi DH, Obembe OO, Ogooluwa AA, Ladele MO, Owonikoko ST, et al. Nicotine exacerbates reproductive biomarkers via generation of free radicals in female Wistar rats: protective role of quercetin. Res J Health Sci. 2021;9(4):378- 88. doi: 10.4314/rejhs.v9i4.6.
  42. Listos J, Łupina M, Talarek S, Mazur A, Orzelska-Górka J, Kotlińska J. The mechanisms involved in morphine addiction: an overview. Int J Mol Sci. 2019;20(17):4302. doi: 10.3390/ ijms20174302.
  43. Waldhoer M, Bartlett SE, Whistler JL. Opioid receptors. Annu Rev Biochem. 2004;73:953-90. doi: 10.1146/annurev. biochem.73.011303.073940.
  44. Bodnar RJ. Endogenous opiates and behavior: 2014. Peptides. 2016;75:18-70. doi: 10.1016/j.peptides.2015.10.009.
  45. Degenhardt L, Whiteford HA, Ferrari AJ, Baxter AJ, Charlson FJ, Hall WD, et al. Global burden of disease attributable to illicit drug use and dependence: findings from the Global Burden of Disease Study 2010. Lancet. 2013;382(9904):1564- 74. doi: 10.1016/s0140-6736(13)61530-5.
  46. Cemek M, Büyükokuroğlu ME, Hazman Ö, Bulut S, Konuk M, Birdane Y. Antioxidant enzyme and element status in heroin addiction or heroin withdrawal in rats: effect of melatonin and vitamin E plus Se. Biol Trace Elem Res. 2011;139(1):41-54. doi: 10.1007/s12011-010-8634-0.
  47. Kosten TR, George TP. The neurobiology of opioid dependence: implications for treatment. Sci Pract Perspect. 2002;1(1):13- 20. doi: 10.1151/spp021113.
  48. Koehl JL, Zimmerman DE, Bridgeman PJ. Medications for management of opioid use disorder. Am J Health Syst Pharm. 2019;76(15):1097-103. doi: 10.1093/ajhp/zxz105.
  49. Lewanowitsch T, Miller JH, Irvine RJ. Reversal of morphine, methadone and heroin induced effects in mice by naloxone methiodide. Life Sci. 2006;78(7):682-8. doi: 10.1016/j. lfs.2005.05.062.
  50. Duberstein JL, Kaufman DM. A clinical study of an epidemic of heroin intoxication and heroin-induced pulmonary edema. Am J Med. 1971;51(6):704-14. doi: 10.1016/0002- 9343(71)90298-1.
  51. Brust JC. Vasculitis owing to substance abuse. Neurol Clin. 1997;15(4):945-57. doi: 10.1016/s0733-8619(05)70357-1.
  52. Cheng MY, Chin SC, Chang YC, Wu T, Lim SN, Hsieh HY, et al. Different routes of heroin intake cause various heroin-induced leukoencephalopathies. J Neurol. 2019;266(2):316-29. doi: 10.1007/s00415-018-9131-1.
  53. Offiah C, Hall E. Heroin-induced leukoencephalopathy: characterization using MRI, diffusion-weighted imaging, and MR spectroscopy. Clin Radiol. 2008;63(2):146-52. doi: 10.1016/j.crad.2007.07.021.
  54. Dujmovic I, Nikolic I, Martinovic V, Mesaros S, Drulovic J. Heroin-induced acute longitudinally extensive transverse myelopathy. Neurol Sci. 2018;39(4):791-2. doi: 10.1007/ s10072-017-3197-x.
  55. Büttner A, Mall G, Penning R, Weis S. The neuropathology of heroin abuse. Forensic Sci Int. 2000;113(1-3):435-42. doi: 10.1016/s0379-0738(00)00204-8.
  56. Zhu M, Zhou X, Zhao J. Quercetin prevents alcohol-induced liver injury through targeting of PI3K/Akt/nuclear factor-κB and STAT3 signaling pathway. Exp Ther Med. 2017;14(6):6169-75. doi: 10.3892/etm.2017.5329.
  57. Anand SK, Ahmad MH, Sahu MR, Subba R, Mondal AC. Detrimental effects of alcohol-induced inflammation on brain health: from neurogenesis to neurodegeneration. Cell Mol Neurobiol. 2023;43(5):1885-904. doi: 10.1007/s10571-022- 01308-2.
Journal of Kerman University of Medical Sciences
Volume 32
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