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The Antioxidant, Anti-Inflammatory, and Sedative Effects of Melatonin: Results of Clinical Trials

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We present published data (clinical trials and systematic reviews) of the antioxidant and anti-inflammatory effects of melatonin. The results of studies published in recent years on these effects in humans and animals are summarized. Melatonin has been shown to protect the cardiovascular system from damage induced by ischemia/reperfusion when given promptly; it has a neuroprotective effect in neonates after asphyxia; it is an effective agent in the complex treatment of irritable bowel syndrome and inflammatory gut disorders (Crohn’s disease and ulcerative colitis). It is also regarded as a premedication agent, decreasing anxiety for surgery, potentially allowing prescription of benzodiazepines to be avoided.

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References

  1. A. Anighoro, J. Bajorath, and G. Rastelli, “Polypharmacology: Challenges and opportunities in drug discovery,” J. Med. Chem., 57, 7874–7887 (2014), https://doi.org/10.1021/jm5006463.

    Article  CAS  Google Scholar 

  2. R. J. Reiter, J. C. Mayo, D. X. Tan, R. M. Sainz, M. Alatorre-Jimenez, and L. Qin, “Melatonin as an antioxidant: under promises but overdelivers,” J. Pineal Res., 61, 253–278 (2016), https://doi.org/10.1111/jpi.12360.

    Article  CAS  Google Scholar 

  3. D. L. Carden, and D. N. Granger, “Pathophysiology of ischaemiareperfusion injury,” J. Pathol., 190, 255–266 (2000), https://doi.org/10.1002/(SICI)1096-9896(200002)190:3.

    Article  CAS  Google Scholar 

  4. K. H. Dwaich, F. G. Y. Al-Amran, B. I. M. Al-Sheibani, and H. A. Al-Aubaidy, “Melatonin effects on myocardial ischemia-reperfusion injury: Impact on the outcome in patients undergoing coronary artery bypass grafting surgery,” Int. J. Cardiol., 221, 977–986 (2016), https://doi.org/10.1016/j.ijcard.2016.07.108.

    Article  Google Scholar 

  5. A. E. Denktas, H. V. Anderson, J. McCarthy, and R. W. Smalling, “Total ischemic time,” JACC Cardiovasc. Interv., 4, 599–604 (2011), https://doi.org/10.1016/j.jcin.2011.02.012.

    Article  Google Scholar 

  6. I. Gogenur, B. Kucukakin, L. Panduro Jensen, R. J. Reiter, and J. Rosenberg, “Melatonin reduces cardiac morbidity and markers of myocardial ischemia after elective abdominal aortic aneurism repair: a randomized, placebo-controlled, clinical trial,” J. Pineal Res., 57, 10–15 (2014), https://doi.org/10.1111/jpi.12138.

    Article  Google Scholar 

  7. M. G. Poluektov, and S. L. Tsenteradze, “Potential for the use of melatonin in ischemic stroke,” Farmateka, 7, 31–35 (2013).

    Google Scholar 

  8. E. Ramos, P. Patino, R. J. Reiter, E. Gil-Martin, J. Marco-Contelles, E. Parada, C. Rios, A. Romero, and J. Egea, “Ischemic brain injury: New insights on the protective role of melatonin,” Free Radic. Biol. Med., 104, 32–53 (2017), https://doi.org/https://doi.org/10.1016/j.freeradbiomed.2017.01.005.

  9. Ya. Levin, “Melatonin and vascular brain disease,” Russ. Med. Zh., 26, 1732 (2008).

    Google Scholar 

  10. F. Fulia, E. Gitto, S. Cuzzocrea, R. J. Reiter, L. Dugo, P. Gitto, S. Barberi, S. Cordaro, and I. Barberi, “Increased levels of malondialdehyde and nitrite/nitrate in the blood of asphyxiated newborns: reduction by melatonin,” J. Pineal Res., 31, 343–349 (2001), https://doi.org/10.1034/j.1600-079X.2001.310409.x.

    Article  CAS  Google Scholar 

  11. H. Aly, H. Elmahdy, M. El-Dib, M. Rowisha, M. Awny, T. El- Gohary, M. Elbatch, M. Hamisa, and A. R. El-Mashad, “Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled pilot study,” J. Perinatol., 35, 186–191 (2015), https://doi.org/10.1038/jp.2014.186.

    Article  CAS  Google Scholar 

  12. P. J. Parekh, E. C. Oldfield Iv, V. Challapalli, J. C. Ware, and D. A. Johnson, “Sleep disorders and inflammatory disease activity: chicken or the egg?” Am. J. Gastroenterol., 110, 484–488 (2015), https://doi.org/10.1038/ajg.2014.247.

    Article  Google Scholar 

  13. A. Hungin, P. Whorwell, J. Tack, and F. Mearin, “The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40,000 subjects,” Aliment. Pharmacol. Ther., 17, 643–650 (2003), https://doi.org/10.1046/j.0269-2813.2003.01456.x.

    Article  CAS  Google Scholar 

  14. R. Fass, S. Fullerton, S. Tung, and E. A. Mayer, “Sleep disturbances in clinic patients with functional bowel disorders,” Am. J. Gastroenterol., 95, 1195–2000 (2000), https://doi.org/10.1111/j.1572-0241.2000.02009.x.

    Article  CAS  Google Scholar 

  15. M. M. Heitkemper, C. J. Han, M. E. Jarrett, H. Gu, D. Djukovic, R. J. Shulman, D. Raftery, W. A. Henderson, and K. C. Cain, “Serum tryptophan metabolite levels during sleep in patients with and without irritable bowel syndrome (IBS),” Biol. Res. Nurs., 18, 193–198 (2016), https://doi.org/10.1177/1099800415594251.

    Article  CAS  Google Scholar 

  16. M. Storr, P. Koppitz, A. Sibaev, D. Saur, M. Kurjak, H. Franck, V. Schusdziarra, and H. D. Allescher, “Melatonin reduces non-adrenergic, non-cholinergic relaxant neurotransmission by inhibition of nitric oxide synthase activity in the gastrointestinal tract of rodents in vitro,” J. Pineal Res., 33, 101–108 (2002), https://doi.org/10.1034/j.1600-079X.2002.02909.x.

    Article  CAS  Google Scholar 

  17. W. Lu, K. Gwee, S. Moochhalla, and K. Ho, “Melatonin improves bowel symptoms in female patients with irritable bowel syndrome: a double-blind placebo-controlled study,” Aliment. Pharmacol. Ther., 22, 927–934 (2005), https://doi.org/10.1111/j.1365-2036.2005.02673.x.

    Article  CAS  Google Scholar 

  18. T. Ali, M. F. Madhoun, W. C. Orr, and D. T. Rubin, “Assessment of the relationship between quality of sleep and disease activity in inflammatory bowel disease patients,” Inflamm. Bowel Dis., 19, 2440–2443 (2013), https://doi.org/10.1097/MIB.0b013e3182a0ea54.

    Article  Google Scholar 

  19. A. N. Ananthakrishnan, M. D. Long, C. F. Martin, R. S. Sandler, and M. D. Kappelman, “Sleep disturbance and risk of active disease in patients with Crohn’s disease and ulcerative colitis,” Clin. Gastro-enterol. Hepatol., 11, 965–971 (2013), https://doi.org/10.1016/j.cgh.2013.01.021.

    Article  Google Scholar 

  20. P. Boznańska, P. Wichan, A. Stepień, M. Wiśniewska-Jarosńska, J. Smigielski, K. Szadkowski, and K. Stec-Michalska, “24-hour urinary 6-hydroxymelatonin sulfate excretion in patients with ulcerative colitis,” Pol. Merkur. Lek., 22, 369–372 (2007).

    Google Scholar 

  21. C. Chojnacki, M. Wisniewska-Jarosinska, E. Walecka-Kapica, G. Klupinska, J. Jaworek, and J. Chojnacki, “Evaluation of melatonin effectiveness in the adjuvant treatment of ulcerative colitis,” J. Physiol. Pharmacol., 62, 327–334 (2011).

    CAS  PubMed  Google Scholar 

  22. M. Rapoport (ed.), Melatonin: Perspectives for Clinical Utilization, IMA-PRESS., Moscow (2012).

    Google Scholar 

  23. P. P. Trivedi, G. B. Jena, K. B. Tikoo, and V. Kumar, “Melatonin modulated autophagy and Nrf2 signaling pathways in mice with colitis-associated colon carcinogenesis,” Mol. Carcinog., 55, 255–267 (2016), https://doi.org/10.1002/mc.22274.

    Article  CAS  Google Scholar 

  24. M. G. Poluektov, “Insomnia,” in: Somnology and Sleep Medicine, M. G. Poluektov (ed.) Medforum, Moscow (2016).

  25. C. Garzon, J. M. Guerrero, O. Aramburu, and T. Guzman, “Effect of melatonin administration on sleep, behavioral disorders and hypnotic drug discontinuation in the elderly: a randomized, double-blind, placebo-controlled study,” Aging Clin. Exp. Res., 21, 38–42 (2009), https://doi.org/10.1007/BF03324897.

    Article  CAS  Google Scholar 

  26. F. J. H. A. Vissers, P. G. Knipschild, and H. F. J. M. Crebolder, “Is melatonin helpful in stopping the long-term use of hypnotics? A discontinuation trial,” Pharm. World Sci., 29, 641–646 (2007), https://doi.org/10.1007/s11096-007-9118-y.

    Article  CAS  Google Scholar 

  27. A. Wright, J. Diebold, J. Otal, C. Stoneman, J. Wong, C. Wallace, and M. Duffett, “The effect of melatonin on benzodiazepine discontinuation and sleep quality in adults attempting to discontinue benzodiazepines: A systematic review and meta-analysis,” Drugs Aging, 32, 1009–1018 (2015), https://doi.org/10.1007/s40266-015-0322-5.

    Article  CAS  Google Scholar 

  28. G. H. Guyatt, A. D. Oxman, G. E. Vist, R. Kunz, Y. Falck-Ytter, P. Alonso-Coello, and H. J. Schunemann, “GRADE: An emerging consensus on rating quality of evidence and strength of recommendations,” Chin. J. Evidence-Based Med., 9, 8–11 (2009), https://doi.org/https://doi.org/10.1136/bmj.39489.470347.AD.

  29. D. Ionescu, C. Badescu, A. Ilie, I. Miclutia, C. Iancu, D. Ion, H. Vasian, C. Bondor, I. Acalovschi, and T. Mocan, “Melatonin as premedication for laparoscopic cholecystectomy: a double-blind, placebocontrolled study,” South African J. Anaesth. Analg., 14, 8–11 (2008), https://doi.org/10.1080/22201173.2008.10872555.

    Google Scholar 

  30. M. Karasek, and K. Winczyk, “Melatonin in humans,” J. Physiol. Pharmacol., 57, 19–39 (2006), https://doi.org/https://doi.org/10.1056/NEJM19970 1163360306.

  31. M. V. Hansen, N. L. Halladin, J. Rosenberg, et al., “Melatonin for pre- and postoperative anxiety in adults,” Cochrane Libr. (2015), https://doi.org/10.1002/14651858.CD009861.pub2.Copyright.

  32. J. B. Gross, J. L. Apfelbaum, R. A. Caplan, R. T. Connis, C. J. Cote, D. G. Nickinovich, D. S. Ward, E. M. Weawer, and L. Ydens, “Practice guidelines for the perioperative management of patients with obstructive sleep apnea,” Anesthesiology, 120, 268–286 (2014), https://doi.org/10.1097/ALN.0000000000000053.

    Article  Google Scholar 

  33. L. Pulak and L. Jensen, “Sleep in the intensive care unit: A review,” J. Intensive Care Med., 31, 14–23 (2016), https://doi.org/10.1016/j.ncl.2011.08.004.

    Article  Google Scholar 

  34. J. Karkela, O. Vakkuri, S. Kaukinen, W. Huang, and M. Pasanen, “The influence of anaesthesia and surgery on the circadian rhythm of melatonin,” Acta Anaesthesiol. Scand., 46, 30–36 (2002), https://doi.org/ https://doi.org/10.1034/j.1399-6576.2002.460106.x.

    Article  CAS  PubMed  Google Scholar 

  35. S. R. Lewis, P. Alderson, and A. F. Smith, “Melatonin for the promotion of sleep in the intensive care unit (Protocol),” Cochrane Database Syst. Rev. (2016), https://doi.org/10.1002/14651858.CD012454.

  36. J. T. Sharkey, R. Puttaramu, R. A. Word, and J. Olcese, “Melatonin synergizes with oxytocin to enhance contractility of human myometrial smooth muscle cells,” J. Clin. Endocrinol. Metab., 94, 421–427 (2009), https://doi.org/10.1210/jc.2008-1723.

    Article  CAS  Google Scholar 

  37. L. Marseglia, G. D’Angelo, S. Manti, R. J. Reiter, and E. Gitto, “Potential utility of melatonin in preeclampsia, intrauterine fetal growth retardation, and perinatal asphyxia,” Reprod. Sci., 23, 970–977 (2016), https://doi.org/10.1177/1933719115612132.

    Article  CAS  Google Scholar 

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Correspondence to D. I. Burchakov.

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Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 117, No. 4, Iss. II, Sleep Disorder, pp. 67–73, April, 2017.

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Burchakov, D.I., Uspenskaya, Y.B. The Antioxidant, Anti-Inflammatory, and Sedative Effects of Melatonin: Results of Clinical Trials. Neurosci Behav Physi 49, 54–59 (2019). https://doi.org/10.1007/s11055-018-0691-4

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