The effects of 5-hydroxytryptophan on carrageenan-induced mouse paw oedemas
Palavras-chave:
5-hydroxytryptophan, Anti-Inflammatory agents, Carrageenan, Dietary supplementsResumo
Objective
5-Hydroxytryptophan is the precursor compound of serotonin biosynthesis. The oral absorption of 5-Hydroxytryptophan is close to 100% and, unlike serotonin, it crosses the blood-brain barrier freely. 5-Hydroxytryptophan has been used as a food supplement for many years to treat anxiety and depression. Recent studies have shown that 5-Hydroxytryptophan suppresses the pro-inflammatory mediators and is effective in some inflammatory diseases, such as arthritis and allergic asthma. However, the role of 5-Hydroxytryptophan supplements on acute peripheral inflammation has not been investigated yet. In this study, the in vivo anti-inflammatory activity of 5-Hydroxytryptophan was evaluated with a carrageenan-induced paw oedema test in mice.
Methods
For the investigation of the acute antiinflammatory activity, single oral doses of 5-Hydroxytryptophan (1.5, 5 and 20mg/kg) were given to mice 1.5 hours prior to the carrageenan test. For chronic activity, the same oral doses were administered daily for two weeks prior to the carrageenan test on the 14th day. To induce inflammation, 0.01mL of 2% carrageenan was injected into the paws of mice.
Results
Supplementation with 5-Hydroxytryptophan significantly reduced inflammation in a dose-independent manner which was irrespective of the duration of exposure (per cent inhibition in acute experiments was 35.4%, 20.9%, 24.0%, and per cent inhibition in chronic experiments was 29.5%, 35.3%, 40.8% for the doses of 1.5, 5, and 20mg/kg, respectively).
Conclusion
Our findings demonstrate for the first time that 5-HTP supplements have the potential of suppressing the measures of acute peripheral inflammation. It is suggested that, apart from several diseases where serotonin is believed to play an important role, including depression, patients with inflammatory conditions may also benefit from 5-HTP
Referências
Oh CM, Park S, Kim H. Serotonin as a new therapeutic target for diabetes mellitus and obesity. Diabetes Metab J. 2016;40(2):89-98. https://doi.org/10.4093/dmj.2016.40.2.89
Kim K, Oh CM, Ohara-Imaizumi M, Park S, Namkung J, Yadav VK, et al. Functional role of serotonin in insulin secretion in a diet-induced insulin-resistant state. Endocrinology. 2015;156(2):444-52. https://doi.org/10.1210/en.2014-1687
Natarajan R, Northrop NA, Yamamoto BK. Protracted effects of chronic stress on serotonin-dependent thermoregulation. Stress. 2015;18(6):668-76. https://doi.org/10.3109/10253890.2015.1087502
Sharma A, Castellani RJ, Smith MA, Muresanu DF, Dey PK, Sharma HS. 5-Hydroxytryptophan: a precursor of serotonin influences regional blood-brain barrier breakdown, cerebral blood flow, brain edema formation, and neuropathology. Int Rev Neurobiol. 2019;146:1-44. https://doi.org/10.1016/bs.irn.2019.06.005
Xu D, Fang M, Wang H, Huang L, Xu Q, Xu Z. Enhanced production of 5-hydroxytryptophan through the regulation of L-tryptophan biosynthetic pathway. Appl Microbiol Biotechnol. 2020;104(6):2481-8. https://doi.org/10.1007/s00253-020-10371-y
Jacobsen JPR, Krystal AD, Krishnan KRR, Caron MG. Adjunctive 5-Hydroxytryptophan slow-release for treatment-resistant depression: clinical and preclinical rationale. Trends Pharmacol Sci. 2016;37(11):933-44. https://doi.org/10.1016/j.tips.2016.09.001
Weinberg-Wolf H, Fagan NA, Anderson GM, Tringides M, Dal Monte O, Chang SWC. The effects of 5-hydroxytryptophan on attention and central serotonin neurochemistry in the rhesus macaque. Neuropsychopharmacology. 2018;43(7):1589-98. https://doi.org/10.1038/s41386-017-0003-7
Sudhamani H, Syam Prasad G, Venkataramaiah C, Raju CN, Rajendra W. In silico and in vitro antioxidant activity profiles of urea and thiourea derivatives of 5-hydroxytryptophan. J Recept Signal Transduct Res. 2019;39(4):373-81. https://doi.org/10.1080/10799893.2019.1683864
Kayacan Y, Yazar H, Kisa EC, Ghojebeigloo BE. A novel biomarker explaining the role of oxidative stress in exercise and l-tyrosine supplementation: thiol/disulphide homeostasis. Arch Physiol Biochem. 2018;124(3):232-6. https://doi.org/10.1080/13813455.2017.1388410
Martinez Medina JJ, Naso LG, Perez AL, Rizzi A, Okulik NB, Valcarcel M, et al. Synthesis, characterization, theoretical studies and biological (antioxidant, anticancer, toxicity and neuroprotective) determinations of a copper(II) complex with 5-hydroxytryptophan. Biomed Pharmacother. 2019;111:414-26. https://doi.org/10.1016/j.biopha.2018.12.098
Bae SJ, Lee JS, Kim JM, Lee EK, Han YK, Kim HJ, et al. 5-Hydroxytrytophan inhibits tert-butylhydroperoxide (t-BHP)-induced oxidative damage via the suppression of reactive species (RS) and nuclear factor-kappaB (NF-kappaB) activation on human fibroblast. J Agric Food Chem. 2010;58(10):6387-94. https://doi.org/10.1021/jf904201h
Cheng SC, Van de Veerdonk F, Smeekens S, Joosten LA, Van der Meer JW, Kullberg BJ, et al. Candida albicans dampens host defense by downregulating IL-17 production. J Immunol. 2010;185(4):2450-7. https://doi.org/10.4049/jimmunol.1000756
Chae HS, Kang OH, Choi JG, Oh YC, Lee YS, Jang HJ, et al. 5-hydroxytryptophan acts on the mitogen-activated protein kinase extracellular-signal regulated protein kinase pathway to modulate cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 cells. Biol Pharm Bull. 2009;32(4):553-7. https://doi.org/10.1248/bpb.32.553
Ohgi Y, Futamura T, Kikuchi T, Hashimoto K. Effects of antidepressants on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration. Pharmacol Biochem Behav. 2013;103(4):853-9. https://doi.org/10.1016/j.pbb.2012.12.003
Abdala-Valencia H, Berdnikovs S, McCary CA, Urick D, Mahadevia R, Marchese ME, et al. Inhibition of allergic inflammation by supplementation with 5-hydroxytryptophan. Am J Physiol Lung Cell Mol Physiol. 2012;303(8):L642-60. https://doi.org/10.1152/ajplung.00406.2011
Yang TH, Hsu PY, Meng M, Su CC. Supplement of 5-hydroxytryptophan before induction suppresses inflammation and collagen-induced arthritis. Arthritis Res Ther. 2015;17:364. https://doi.org/10.1186/s13075-015-0884-y
Kantari C, Pederzoli-Ribeil M, Witko-Sarsat V. The role of neutrophils and monocytes in innate immunity. Contrib Microbiol. 2008;15:118-46. https://doi.org/10.1159/000136335
Sarigol D, Uzgoren-Baran A, Tel BC, Somuncuoglu EI, Kazkayasi I, Ozadali-Sari K, et al. Novel thiazolo[3,2-b]-1,2,4-triazoles derived from naproxen with analgesic/anti-inflammatory properties: synthesis, biological evaluation and molecular modeling studies. Bioorg Med Chem. 2015;23(10):2518-28. https://doi.org/10.1016/j.bmc.2015.03.049
Galano A, Castaneda-Arriaga R, Perez-Gonzalez A, Tan DX, Reiter RJ. Phenolic melatonin-related compounds: their role as chemical protectors against oxidative stress. Molecules. 2016;21(11). https://doi.org/10.3390/molecules21111442
Galecki P, Mossakowska-Wojcik J, Talarowska M. The anti-inflammatory mechanism of antidepressants: SSRIs, SNRIs. Prog Neuropsychopharmacol Biol Psychiatry. 2018;80(PtC):291-4. https://doi.org/10.1016/j.pnpbp.2017.03.016
Wu H, Denna TH, Storkersen JN, Gerriets VA. Beyond a neurotransmitter: the role of serotonin in inflammation and immunity. Pharmacol Res. 2019;140:100-14. https://doi.org/10.1016/j.phrs.2018.06.015
Eskeland S, Halvorsen JA, Tanum L. Antidepressants have anti-inflammatory effects that may be relevant to dermatology: a systematic review. Acta Derm Venereol. 2017;97(8):897-905. https://doi.org/10.2340/00015555-2702
Schuff-Werner P, Splettstoesser W. Antioxidative properties of serotonin and the bactericidal function of polymorphonuclear phagocytes. Adv Exp Med Biol. 1999;467:321-5. https://doi.org/10.1007/978-1-4615-4709-9_41
Shajib MS, Khan WI. The role of serotonin and its receptors in activation of immune responses and inflammation. Acta Physiol (Oxf). 2015;213(3):561-74. https://doi.org/10.1111/apha.12430
Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci. 2013;16(5):821-47. https://doi.org/10.18433/j3vw2f
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2022 Gokçen TELLI, Inci KAZKAYASI, Serdar UMA
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.