Antidepressant Effects of a Persian Medicine Remedy on Multiple Sclerosis Patients: A Double-Blinded Randomized Clinical Trial

  • Maryam Adalat Department of Traditional Medicine, School of Traditional Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  • Mohammad Khalili 1. Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran 2. Neurosciences Research Center; Tabriz University of Medical Sciences, Tabriz, Iran
  • Hormoz Ayromlou 1. Neurosciences Research Center; Tabriz University of Medical Sciences, Tabriz, Iran 2. Department of Neurology, Tabriz University of Medical Sciences, Tabriz, Iran
  • Sajjad Haririan Department of Neurology, Alinasab Hospital, Tabriz, Iran
  • Seyyed Mohammad Bagher Fazljou Department of Traditional Medicine, School of Traditional Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  • Hossein Rezaeizadeh Department of Traditional Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Ali Akbar Safari Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Arman Zargaran Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran
Keywords: Persian Medicine, Multiple Sclerosis, Depression, Herbal Extract, Alternative Medicine


Background: Multiple sclerosis (MS), an inflammatory neurodegenerative disease of the central nervous system, is accompanied by some psychiatric disorders, one prominent example of which is depression. The aim of this study was to investigate the effects of a Persian herbal medicine treatment that contains Crocus sativus, Hypericum perforatum, Cinnamon verum, and Vitis vinifera on fatigue and sleep disorders in MS patients. Materials and Methods: A Persian medicine remedy containing C.sativus, H.perforatum, C.verum, and V.vinifera was tested for its ability to improve the symptoms of depression in MS patients. This randomized double-blind clinical study was performed among 52 patients with MS who were allocated to their respective research groups through blocked randomization. The patients were treated for 4 weeks with either the drug or the placebo. To quantify the symptoms of depression, Beck depression inventory (BDI) was used. Results: Forty-six patients completed the study. In the course of the study, as the primary outcome, BDI decreased in the drug group (p=0.000) and the placebo group (p=0.001) significantly, but the rate of change in the drug group was significantly higher than in the placebo group (-13.9 ± 8.6 vs. -3.9 ± 4.3, p=0.000). While analyzing time and treatment effect for BDI, significant decreases in BDI were observed for the drug group, but not in the placebo group (p= 0.001). Conclusion: The present study suggests that Persian medicine remedy treatment in combination with chemical drugs may improve depression symptoms in MS patients. More investigations are needed to discover the exact mechanisms and processes involved. [GMJ.2019;8:e1212]


McGuigan C, Hutchinson M. Unrecognised symptoms of depression in a community-based population with multiple sclerosis. J Neurol. 2006;253(2):219-23.


Khalili M, Eghtesadi S, Mirshafiey A, Eskandari G, Sanoobar M, Sahraian MA et al. Effect of lipoic acid consumption on oxidative stress among multiple sclerosis patients: a randomized controlled clinical trial. Nutr Neurosci. 2014;17(1):16-20.


Raskind MA. Diagnosis and Treatment of Depression Comorbid with Neurologic Disorders. Am J Med. 2008;121(11):S28-S37.


Sanoobar M, Dehghan P, Khalili M, Azimi A, Seifar F. Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: a double blind randomized clinical trial. Nutr Neurosci. 2016;19(3):138-43.


Giordano A, Granella F, Lugaresi A, Martinelli V, Trojano M, Confalonieri P et al. Anxiety and depression in multiple sclerosis patients around diagnosis. J Neurol Sci. 2011;307(1):86-91.


Ziemssen T. Multiple sclerosis beyond EDSS: depression and fatigue. J Neurol Sci. 2009;277:S37-S41.

Thachil AF, Mohan R, Bhugra D. The evidence base of complementary and alternative therapies in depression. J Affect Disord. 2007;97(1):23-35.


Dayapoglu N, Tan M. Use of complementary and alternative medicine among people with multiple sclerosis in Eastern Turkey. Neurol Asia. 2016;21(1): 63-71.

Sarris J, Panossian A, Schweitzer I, Stough C, Scholey A. Herbal medicine for depression, anxiety and insomnia: A review of psychopharmacology and clinical evidence. Eur Neuropsychopharmacol. 2011;21(12):841-60.


Akhondzadeh S. Herbal medicines in the treatment of psychiatric and neurological disorders. Low-Cost Approaches to Promote Physical and Mental Health. 2007:119-138.

Bahmani M, Zargaran A. Ethno-botanical medicines used for urinary stones in the Urmia, Northwest Iran. Eur J Integr Med. 2015;7(6):657-62.

Makhzan-ol-Advieh AM. Storehouse of Medicaments. Intisharat va Amoozesh Enghelab Islami Press, Tehran, Iran. 1992.

Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: A meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(1):118-127.


Nosratabadi R, Rastin M, Sankian M, Haghmorad D, Tabasi N, Zamani S et al. St. John's wort and its component hyperforin alleviate experimental autoimmune encephalomyelitis through expansion of regulatory T-cells. J Immunotoxicol. 2016;13(3):364-374.


Sohrabi R, Pazgoohan N, Seresht HR, Amin B. Repeated systemic administration of the cinnamon essential oil possesses anti-anxiety and antidepressant activities in mice. Iran J Basic Med Sci. 2017;20(6):708-714.

Frydman-Marom A, Levin A, Farfara D, Benromano T, Scherzer-Attali R, Peled S et al. Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models. PLoS One. 2011;6(1):e16564.

PMid:21305046 PMCid:PMC3030596

Waggas AM. Grape seed extract (Vitisvinifera) alleviate neurotoxicity and hepatotoxicity induced by lead acetate in male albino rats. J Behav Brain Sci. 2012;2(02):176-184.

Fonseca-Kelly Z, Nassrallah M, Uribe J, Khan RS, Dine K, Dutt M et al. Resveratrol neuroprotection in a chronic mouse model of multiple sclerosis. Front Neurol. 2012;3.

PMid:22654783 PMCid:PMC3359579

Basti AA, Moshiri E, Noorbala A-A, Jamshidi A-H, Abbasi SH, Akhondzadeh S. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(2):439-442.


Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi A-H, Khalighi-Cigaroudi F. 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. 2004;4(1):12.

PMid:15341662 PMCid:PMC517724

McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121-127.


Moran PJ, Mohr DC. The validity of Beck Depression Inventory and Hamilton Rating Scale for Depression items in the assessment of depression among patients with multiple sclerosis. J Behav Med. 2005;28(1):35-41.


Amin KA, Nagy MA. Effect of Carnitine and herbal mixture extract on obesity induced by high fat diet in rats. Diabetol Metab Syndr. 2009;1(1):17.

PMid:19835614 PMCid:PMC2772188

Moshiri E, Basti AA, Noorbala A-A, Jamshidi A-H, Abbasi SH, Akhondzadeh S. Crocus sativus L.(petal) in the treatment of mild-to-moderate depression: A double-blind, randomized and placebo-controlled trial. Phytomedicine. 2006;13(9):607-611.


Woelk H. Comparison of St John's wort and imipramine for treating depression: randomised controlled trial. Bmj. 2000;321(7260):536-539.

PMid:10968813 PMCid:PMC27467

Szegedi A, Kohnen R, Dienel A, Kieser M. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine. Bmj. 2005;330(7490):503.

PMid:15708844 PMCid:PMC552808

Lecrubier Y, Clerc G, Didi R, Kieser M. Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Am J Psychiatry. 2002;159(8):1361-6.


Yoshitake T, Iizuka R, Yoshitake S, Weikop P, Müller WE, Ögren SO et al. Hypericum perforatum L (St John's wort) preferentially increases extracellular dopamine levels in the rat prefrontal cortex. Br J Pharmacol. 2004;142(3):414-418.

PMid:15148244 PMCid:PMC1574978

Butterweck V. Mechanism of action of St John's wort in depression. CNS Drugs. 2003;17(8):539-62.


Chang Y, Wang S-J. Hypericin, the active component of St. John's wort, inhibits glutamate release in the rat cerebrocortical synaptosomes via a mitogen-activated protein kinase-dependent pathway. Eur J Pharmacol. 2010;634(1):53-61.


Maes M, Galecki P, Chang YS, Berk M. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro) degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(3):676-692.


Roussel A-M, Hininger I, Benaraba R, Ziegenfuss TN, Anderson RA. Antioxidant effects of a cinnamon extract in people with impaired fasting glucose that are overweight or obese. J Am Coll Nutr. 2009;28(1):16-21.


Moselhy SS, Ali HK. Hepatoprotective effect of cinnamon extracts against carbon tetrachloride induced oxidative stress and liver injury in rats. Biol Res. 2009;42(1):93-98.


Jana A, Modi KK, Roy A, Anderson JA, Van Breemen RB, Pahan K. Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders. J Neuroimmune Pharmacol. 2013;8(3):739-755.

PMid:23475543 PMCid:PMC3663914

Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry J-M. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res. 2002;109(2):143-8.

Hurley LL, Akinfiresoye L, Kalejaiye O, Tizabi Y. Antidepressant effects of resveratrol in an animal model of depression. Behav Brain Res. 2014;268:1-7.

PMid:24717328 PMCid:PMC4033784

Pang C, Cao L, Wu F, Wang L, Wang G, Yu Y et al. The effect of trans-resveratrol on post-stroke depression via regulation of hypothalamus-pituitary-adrenal axis. Neuropharmacology. 2015;97:447-56.


Ahmed RF, Abdel-Rahman RF, Farid OA, El-Marasy SA, Hessin AF. Combined hepatoprotective and antidepressant effects of resveratrol in an acute model of depression. Bulletin of Faculty of Pharmacy, Cairo University. 2014;52(2):191-197.

Xu Y, Li S, Chen R, Li G, Barish PA, You W et al. Antidepressant-like effect of low molecular proanthocyanidin in mice: Involvement of monoaminergic system. Pharmacol Biochem Behav. 2010;94(3):447-453.


Lee G, Bae H. Therapeutic Effects of Phytochemicals and Medicinal Herbs on Depression. Biomed Res Int. 2017;2017.

PMid:28503571 PMCid:PMC5414506

Ge J-F, Peng L, Cheng J-Q, Pan C-X, Tang J, Chen F-H et al. Antidepressant-like effect of resveratrol: involvement of antioxidant effect and peripheral regulation on HPA axis. Pharmacol Biochem Behav. 2013;114:64-69.


Richard T, Pawlus AD, Iglésias ML, Pedrot E, Waffo‐Teguo P, Mérillon JM et al. Neuroprotective properties of resveratrol and derivatives. Ann N Y Acad Sci. 2011;1215(1):103-108.


Hausenblas HA, Saha D, Dubyak PJ, Anton SD. Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. J Integr Med. 2013;11(6):377-383.

PMid:24299602 PMCid:PMC4643654

Christodoulou E, Kadoglou NP, Kostomitsopoulos N, Valsami G. Saffron: a natural product with potential pharmaceutical applications. J Pharm Pharmacol. 2015;67(12):1634-1649.


Ghazavi A, Mosayebi G, Salehi H, Abtahi H. Effect of ethanol extract of saffron (Crocus sativus L.) on the inhibition of experimental autoimmune encephalomyelitis in C57bl/6 mice. Pak J Biol Sci. 2009;12(9):690-695.


Nam KN, Park Y-M, Jung H-J, Lee JY, Min BD, Park S-U et al. Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. Eur J Pharmacol. 2010;648(1):110-116.


How to Cite
Adalat, M., Khalili, M., Ayromlou, H., Haririan, S., Fazljou, S. M. B., Rezaeizadeh, H., Safari, A. A., & Zargaran, A. (2019). Antidepressant Effects of a Persian Medicine Remedy on Multiple Sclerosis Patients: A Double-Blinded Randomized Clinical Trial. Galen Medical Journal, 8, e1212.
Original Article