Evaluation of the effectiveness of crocin isolated from saffron in treatment of burning mouth syndrome: A randomized controlled trial

Document Type : Original Research Article

Authors

1 Oral and Maxillofacial Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Family Medicine Department, Faculty of Psychiatry, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

4 Oral & Maxillofacial specialist, Department of Oral Health, Gonabad University of Medical Sciences, Gonabad, Iran.

Abstract

Objective: Burning mouth syndrome (BMS) is a debilitating disorder with few limited treatment modalities. Because of the proven association between BMS symptoms, and depression and anxiety, treatment modalities that alleviate the two latter etiologic factors can be clinically effective. Thus, owing to the antidepressant and potential analgesic effects of crocin (as an active constituent of saffron), the present study was performed to compare the effect of crocin and citalopram (as control) on BMS symptoms and depression/anxiety in patients with BMS.
Materials and Methods: The present double-blind randomized clinical trial was carried out on BMS patients. Patients were randomly divided into citalopram (n=21) and crocin (n=26) groups and treated for 11 weeks. BMS symptoms (based on Visual Analysis Scale (VAS)), as well as anxiety and depression (based on Hamilton questionnaire) were evaluated at baseline and during the treatment period.  Mann-Whitney, Chi-Square test, Independent t-test, Friedman, and Spearman correlation were employed for statistical analysis.
Results: Our findings showed a significant effect for crocin on the severity of BMS symptoms, anxiety and depression in BMS patients.
Conclusion: Crocin can be considered for treatment of BMS subjects with concurrent anxiety and/or depression.

Keywords

Main Subjects

References

Abdullaev FI. 2002. Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.). Exp Biol Med (Maywood),227: 20-25.
Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi A,  Khalighi-Cigaroudi F. 2004. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816]. BMC Complement Altern Med,4:12.
Akhondzadeh S, Sabet MS, Harirchian MH, Togha M, Cheraghmakani H, Razeghi S, Hejazi S, Yousefi MH, Alimardani R, Jamshidi A, Zare F,  Moradi A. 2010. Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial. J Clin Pharm Ther,35: 581-588.
Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, Amini H, Fallah-Pour H, Jamshidi AH,  Khani M. 2005. Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial. Phytother Res,19: 148-151.
Amin B,  Hosseinzadeh H. 2012. Evaluation of aqueous and ethanolic extracts of saffron, Crocus sativus L., and its constituents, safranal and crocin in allodynia and hyperalgesia induced by chronic constriction injury model of neuropathic pain in rats. Fitoterapia,83: 888-895.
Baharvand M, Rafieian N,  Bakhtiari S. 2010. Review article of Burning mouth syndrome (BMS)J Dent Sch Shahid Beheshti Univ Med Sci. J Dent Sch Shahid Beheshti Univ Med Sci,28: 172-179.
Bartoshuk LM, Grushka M, Duffy VB, Fast K, Lucchina L, Prutkin J,  Synder D. 1999. Burning mouth syndrome: damage to CN VII and pain phantoms in CN V. Chemical Senses, 24: 609-618.
Benoliel R, Ananthan S, Zagury J, Khan J,  Eliav E. 2015. Orofacial pain. In:  Glick M (Eds), Burket's Oral Medicine, p. 319, Netherlands, Elsevier.
Bergdahl J, Anneroth G,  Ferris H. 1995. Cognitive therapy in the treatment of patients with resistant burning mouth syndrome: a controlled study. J Oral Pathol Med,24: 213-215.
Bergdahl M,  Bergdahl J. 1999. Burning mouth syndrome: prevalence and associated factors. J Oral Pathol Med,28: 350-354.
Berger F, Hensel A,  Nieber K. 2011. Saffron extract and trans-crocetin inhibit glutamatergic synaptic transmission in rat cortical brain slices. Neuroscience,180: 238-247.
Borelli V, Marchioli A, Di Taranto R, Romano M, Chiandussi S, Di Lenarda R, Biasotto M,  Zabucchi G. 2010. Neuropeptides in saliva of subjects with burning mouth syndrome: a pilot study. Oral Dis,16: 365-374.
Botha PJ, van der Bijl P,  van Eyk AD. 2001. A literature review and pilot study to characterise the treatment of burning mouth syndrome. Sadj,56: 353-358.
Carlson CR, Miller CS,  Reid KI. 2000. Psychosocial profiles of patients with burning mouth syndrome. J Orofac Pain,14: 59-64.
Cole JA, Ephross SA, Cosmatos IS,  Walker AM. 2007. Paroxetine in the first trimester and the prevalence of congenital malformations. Pharmacoepidemiol Drug Saf,16: 1075-1085.
de Moraes M, do Amaral Bezerra BA, da Rocha Neto PC, de Oliveira Soares AC, Pinto LP,  de Lisboa Lopes Costa A. 2012. Randomized trials for the treatment of burning mouth syndrome: an evidence-based review of the literature. J Oral Pathol Med,41: 281-287.
de Souza FT, Teixeira AL, Amaral TM, dos Santos TP, Abreu MH, Silva TA,  Kummer A. 2012. Psychiatric disorders in burning mouth syndrome. J Psychosom Res,72: 142-146.
Dwyer A, Whitten D,  Hawrelak J. 2011. Herbal medicines, other than St. John's Wort, in the treatment of depression: a systematic review. Altern Med Rev,16: 40-49.
Ebrahimi H, Pourshahidi S,  Tadbir AA. 2009. The effect of citalopram and colonazpam on burning mouth syndrome. Shiraz Univ Dent J,9: 31-34.
Femiano F. 2002. Burning mouth syndrome (BMS): an open trial of comparative efficacy of alpha-lipoic acid (thioctic acid) with other therapies. Minerva Stomatol,51: 405-409.
Femiano F, Gombos F,  Scully C. 2004. Burning Mouth Syndrome: open trial of psychotherapy alone, medication with alpha-lipoic acid (thioctic acid), and combination therapy. Med Oral,9: 8-13.
Ferguson JM. 2001. SSRI Antidepressant Medications: Adverse Effects and Tolerability. Prim Care Companion J Clin Psychiatry,3: 22-27.
Forssell H, Jaaskelainen S, Tenovuo O,  Hinkka S. 2002. Sensory dysfunction in burning mouth syndrome. Pain,99: 41-47.
Fukui H, Toyoshima K,  Komaki R. 2011. Psychological and neuroendocrinological effects of odor of saffron (Crocus sativus). Phytomedicine,18: 726-730.
Georgiadou G, Tarantilis PA,  Pitsikas N. 2012. Effects of the active constituents of Crocus Sativus L., crocins, in an animal model of obsessive-compulsive disorder. Neurosci Lett,528: 27-30.
Ghajar A, Neishabouri SM, Velayati N, Jahangard L, Matinnia N, Haghighi M, Ghaleiha A, Afarideh M, Salimi S, Meysamie A,  Akhondzadeh S. 2017. Crocus sativus L. versus citalopram in the treatment of major depressive disorder with anxious distress: a double-blind, controlled clinical trial. Pharmacopsychiatry,50: 152-160.
Ghasemi T, Abnous K, Vahdati F, Mehri S, Razavi BM,  Hosseinzadeh H. 2015. Antidepressant effect of crocus sativus aqueous extract and its effect on CREB, BDNF, and VGF transcript and protein levels in rat hippocampus. Drug Res (Stuttg),65: 337-343.
Giaccio M. 2004. Crocetin from saffron: an active component of an ancient spice. Crit Rev Food Sci Nutr,44: 155-172.
Greenberg M, Glick M,  Ship J. 2008. Burket's Oral Medicine. Spain, BC Decker Inc, pp. 285.
Gremeau-Richard C, Woda A, Navez ML, Attal N, Bouhassira D, Gagnieu MC, Laluque JF, Picard P, Pionchon P,  Tubert S. 2004. Topical clonazepam in stomatodynia: a randomised placebo-controlled study. Pain,108: 51-57.
Hadizadeh F, Mohajeri SA,  Seifi M. 2010. Extraction and purification of crocin from saffron stigmas employing a simple and efficient crystallization method. Pak J Biol Sci,13: 691-698.
Hakeberg M, Berggren U, Hägglin C,  Ahlqwist M. 1997. Reported burning mouth symptoms among middle-aged and elderly women. European Journal of Oral Sciences,105: 539-543.
Hausenblas HA, Saha D, Dubyak PJ,  Anton SD. 2013. Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. J Integr Med,11: 377-383.
Heckmann SM, Heckmann JG, Ungethum A, Hujoel P,  Hummel T. 2006. Gabapentin has little or no effect in the treatment of burning mouth syndrome - results of an open-label pilot study. Eur J Neurol,13: e6-7.
Hershkovich O,  Nagler R. 2004. Biochemical analysis of saliva and taste acuity evaluation in patients with burning mouth syndrome, xerostomia and/or gustatory disturbances. Arch Oral Biol,49: 515-522.
Kamalipour M, Jamshidi AH,  Akhondzadeh S. 2010. Antidepressant effect of Crocus sativus: An evidence based review. J Med Plant,9: 35-38.
Kashani L, Esalatmanesh S, Eftekhari F, Salimi S, Foroughifar T, Etesam F, Safiaghdam H, Moazen-Zadeh E,  Akhondzadeh S. 2018. Efficacy of Crocus sativus (saffron) in treatment of major depressive disorder associated with post-menopausal hot flashes: a double-blind, randomized, placebo-controlled trial. Arch Gynecol Obstet,297: 717-724.
Kashani L, Eslatmanesh S, Saedi N, Niroomand N, Ebrahimi M, Hosseinian M, Foroughifar T, Salimi S,  Akhondzadeh S. 2017. Comparison of saffron versus fluoxetine in treatment of mild to moderate postpartum depression: a double-blind, randomized clinical trial. Pharmacopsychiatry,50: 64-68.
Kato IT, Pellegrini VD, Prates RA, Ribeiro MS, Wetter NU,  Sugaya NN. 2010. Low-level laser therapy in burning mouth syndrome patients: a pilot study. Photomed Laser Surg,28: 835-839.
Khalatbari-Mohseni A, Banafshe HR, Mirhosseini N, Asemi Z, Ghaderi A,  Omidi A. 2019. The effects of crocin on psychological parameters in patients under methadone maintenance treatment: a randomized clinical trial. Subst Abuse Treat Prev Policy,14: 9.
Khazdair M, Boskabady M, Hosseini M, Rezaee R,  A MT. 2015. The effects of Crocus sativus (saffron) and its constituents on nervous system: A review. Avicenna J Phytomed,5: 376-391.
Klasser GD, Fischer DJ,  Epstein JB. 2008. Burning mouth syndrome: recognition, understanding, and management. Oral Maxillofac Surg Clin North Am,20: 255-271.
Kohorst J, Bruce A, Torgerson R, Schenck L,  Davis M. 2015. The prevalence of burning mouth syndrome: a population-based study. Br J Dermatol,172: 1654-1656.
Kohorst JJ, Bruce AJ, Torgerson RR, Schenck LA,  Davis MD. 2014. A population-based study of the incidence of burning mouth syndrome. Mayo Clin Proc,89: 1545-1552.
Komiyama O, Nishimura H, Makiyama Y, Iida T, Obara R, Shinoda M, Kobayashi M, Noma N, Abe O, De Laat A,  Kawara M. 2013. Group cognitive-behavioral intervention for patients with burning mouth syndrome. J Oral Sci,55: 17-22.
Lamey PJ, Freeman R, Eddie SA, Pankhurst C,  Rees T. 2005. Vulnerability and presenting symptoms in burning mouth syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod,99: 48-54.
Lamey PJ,  Lamb AB. 1988. Prospective study of aetiological factors in burning mouth syndrome. Br Med J (Clin Res Ed),296: 1243-1246.
Lauria G, Majorana A, Borgna M, Lombardi R, Penza P, Padovani A,  Sapelli P. 2005. Trigeminal small-fiber sensory neuropathy causes burning mouth syndrome. Pain,115: 332-337.
León Espinosa S, López Jornet P,  Frutos Ros R. 2004. Síndrome de boca ardiente: Eficacia de la aplicación tópica de capsaicina. Estudio piloto. Avances en Odontoestomatología,297-304.
Maina G, Vitalucci A, Gandolfo S,  Bogetto F. 2002. Comparative efficacy of SSRIs and amisulpride in burning mouth syndrome: a single-blind study. J Clin Psychiatry,63: 38-43.
Marino R, Ardore M, Ferro G, Gandolfo S,  Pentenero M. 2014. Prevalence of psychiatric disorders in patients with burning mouth syndrome. Annali di stomatologia,5: 31-37.
Mazidi M, Shemshian M, Mousavi SH, Norouzy A, Kermani T, Moghiman T, Sadeghi A, Mokhber N, Ghayour-Mobarhan M,  Ferns GA. 2016. A double-blind, randomized and placebo-controlled trial of Saffron (Crocus sativus L.) in the treatment of anxiety and depression. J Complement Integr Med,13: 195-199.
Milajerdi A, Akhonzadeh S, Jazayeri S, Shirzadi E, Hashemzadeh N, Derakhshan Z, Djazayeri A,  Mahmoodi M. 2016. The effect of saffron (Crocus sativus L.) hydro-alcoholic extract on mild to moderate mixed depression-anxiety treatment in type 2 diabetes: a triple-blind randomized placebo-controlled clinical trial. Iran J Nutr Sci Food Technol,11: 11-20.
Miller A, Miller I, Kurnatowska A,  Rabe-Jabłońska J. 2004. The Burning Mouth Syndrome (BMS) alleviation after  treatment with Citalopram in BMS patients with associated anxiety or depressive disorders or without mental  health problems. Postępy Psych Neur,13: 201-214.
Miller A,  Rabe-Jablonska J. 2003. P.1.083 Efficacy of citalopram treatment in subjects with burning mouth syndrome with and without depressive disorders. European Neuropsychopharmacology,13: S209-S210.
Minguez Serra MP, Salort Llorca C,  Silvestre Donat FJ. 2007. Pharmacological treatment of burning mouth syndrome: A review and update. Med Oral Patol Oral Cir Bucal,12: E299-304.
Modabbernia A,  Akhondzadeh S. 2013. Saffron, passionflower, valerian and sage for mental health. Psychiatr Clin North Am,36: 85-91.
Moshiri E, Basti AA, Noorbala AA, Jamshidi AH, Hesameddin Abbasi S,  Akhondzadeh S. 2006. Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trial. Phytomedicine,13: 607-611.
Netto FO, Diniz IM, Grossmann SM, de Abreu MH, do Carmo MA,  Aguiar MC. 2011. Risk factors in burning mouth syndrome: a case-control study based on patient records. Clin Oral Investig,15: 571-575.
Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N,  Jamshidi AH. 2005. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial. J Ethnopharmacol,97: 281-284.
Pashirzad M, Shafiee M, Avan A, Ryzhikov M, Fiuji H, Bahreyni A, Khazaei M, Soleimanpour S,  Hassanian SM. 2019. Therapeutic potency of crocin in the treatment of inflammatory diseases: Current status and perspective. J Cell Physiol.[Epub ahead of print].
Pitsikas N, Boultadakis A, Georgiadou G, Tarantilis PA,  Sakellaridis N. 2008. Effects of the active constituents of Crocus sativus L., crocins, in an animal model of anxiety. Phytomedicine,15: 1135-1139.
Pokupec-Gruden JS, Cekic-Arambasin A,  Gruden V. 2000. Psychogenic factors in the aetiology of stomatopyrosis. Coll Antropol,24 Suppl 1: 119-126.
Ríos JL, Recio MC, Giner RM,  Máñez S. 1996. An update review of saffron and its active constituents. Phytother Res,10: 189-193.
Sahraian A, Jelodar S, Javid Z, Mowla A,  Ahmadzadeh L. 2016. Study the effects of saffron on depression and lipid profiles: A double blind comparative study. Asian J Psychiatr,22: 174-176.
Sardella A, Lodi G, Demarosi F, Uglietti D,  Carrassi A. 2006. Causative or precipitating aspects of burning mouth syndrome: a case-control study. J Oral Pathol Med,35: 466-471.
Sardella A, Uglietti D, Demarosi F, Lodi G, Bez C,  Carrassi A. 1999. Benzydamine hydrochloride oral rinses in management of burning mouth syndrome. A clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol Endod,88: 683-686.
Scala A, Checchi L, Montevecchi M, Marini I,  Giamberardino MA. 2003. Update on burning mouth syndrome: overview and patient management. Crit Rev Oral Biol Med,14: 275-291.
Silvestre FJ, Silvestre-Rangil J, Tamarit-Santafe C,  Bautista D. 2012. Application of a capsaicin rinse in the treatment of burning mouth syndrome. Med Oral Patol Oral Cir Bucal,17: e1-4.
Spanemberg JC, Rodriguez de Rivera Campillo E, Salas EJ,  Lopez Lopez J. 2014. Burning Mouth Syndrome: update. Oral Health Dent Manag,13: 418-424.
Tabeshpour J, Sobhani F, Sadjadi SA, Hosseinzadeh H, Mohajeri SA, Rajabi O, Taherzadeh Z,  Eslami S. 2017. A double-blind, randomized, placebo-controlled trial of saffron stigma (Crocus sativus L.) in mothers suffering from mild-to-moderate postpartum depression. Phytomedicine,36: 145-152.
Talaei A, Hassanpour Moghadam M, Sajadi Tabassi SA,  Mohajeri SA. 2015. Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: a randomized, double-blind, placebo-controlled, pilot clinical trial. J Affect Disord,174: 51-56.
Umezaki Y, Badran BW, Gonzales TS,  George MS. 2015. Daily left prefrontal repetitive transcranial magnetic stimulation for medication-resistant burning mouth syndrome. Int J Oral Maxillofac Surg,44: 1048-1051.
Wang Y, Han T, Zhu Y, Zheng CJ, Ming QL, Rahman K,  Qin LP. 2010. Antidepressant properties of bioactive fractions from the extract of Crocus sativus L. J Nat Med,64: 24-30.
Woda A, Dao T,  Gremeau-Richard C. 2009. Steroid dysregulation and stomatodynia (burning mouth syndrome). J Orofac Pain,23: 202-210.
Yamazaki Y, Hata H, Kitamori S, Onodera M,  Kitagawa Y. 2009. An open-label, noncomparative, dose escalation pilot study of the effect of paroxetine in treatment of burning mouth syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod,107: e6-11.
Zakrzewska JM, Forssell H,  Glenny AM. 2005. Interventions for the treatment of burning mouth syndrome. Cochrane Database Syst Rev: Cd002779.
Avicenna Journal of Phytomedicine
Volume 9, Issue 6
November and December 2019
Pages 505-516

Files

Share

How to cite

Statistics