Effect of Nigella sativa oil extracts on inflammatory and oxidative stress markers in Behcet’s disease: A randomized, double-blind, placebo-controlled clinical trial

Document Type : Original Research Article


1 Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

3 Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

4 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

5 Barij Essence Medicinal Plants Research Center, Kashan, Iran


Objective: Behcet's disease (BD) is a chronic inflammatory disorder characterized by recurrent oral and genital aphthous ulcers, uveitis and skin lesions. Oxidative stress and inflammation have important role in the pathogenesis of BD. The aim of this study was to assess the effect of Nigella sativa (NS) oil administration on malondialdehyde (MDA), total anti-oxidant capacity (TAC), tumor necrosis factor-α (TNF-α), IL-10 and high sensitivity C-reactive protein (hs- CRP) levels in patients with BD.
Materials and Methods: In this randomized, double-blind and placebo-controlled clinical trial, 96 BD patients were randomly assigned to NS or placebo groups. Study groups received 1000 mg/day NS oil and placebo soft gels for 8 weeks. Serum levels of TNF-α, IL-10, hs-CRP, MDA and TAC were measured before and after treatment.
Results: Eighty-nine individuals completed the study. Significant decreases in the serum levels of MDA and increases in the serum levels of TAC were found in the NS group. However, differences in the changes of MDA and TAC in the NS and placebo groups were not significant. Pre- and post-intervention changes of TNF-α, IL-10 and hs-CRP levels in the NS group were non-significant.
Conclusion: NS 1000 mg per day is probably not effective in reducing the inflammatory and oxidative markers in BD.


Ahmed MA, Hassanein KM. 2013. Cardio protective effects of Nigella sativa oil on lead induced cardio toxicity: Anti inflammatory and antioxidant mechanism. J Physiol Pathophysiol, 4: 72-80.
Alipour S, Nouri M, Sakhinia E, Samadi N, Roshanravan N, Ghavami A, Khabbazi, A. 2017. Epigenetic alterations in chronic disease focusing on Behcet’s disease: Review. Biomed Pharmacother, 91: 526-533.
Bilici M, Efe H, Köroğlu MA, Uydu HA, Bekaroğlu M, Değer O. 2001. Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. J Affect Disord, 64: 43-51.
Budancamanak M, Kanter M, Demirel A, Ocakci A, Uysal H, Karakaya C. 2006. Protective effects of thymoquinone and methotrexate on the renal injury in collagen-induced arthritis. Arch Toxicol, 80: 768-776.
Davatchi F, Chams-Davatchi C, Shams H, Shahram F, Nadji A, Akhlaghi M, Faezi T, Ghodsi Z, Sadeghi Abdollahi B, Ashofteh F, Mohtasham N, Kavosi H, Masoumi M. 2017. Behcet's disease: epidemiology, clinical manifestations, and diagnosis. Expert Rev Clin Immunol, 13: 57-65.
Davatchi F, Assaad-Khalil S, Calamia KT, Crook JE, Sadeghi-Abdollahi B, Schirmer M, Tzellos T, Zouboulis CC, Akhlagi M, Al-Dalaan A, Alekberova ZS, Ali AA, Altenburg A, Arromdee E, Baltaci M, Bastos M, Benamour S, Ghorbel I, Boyvat A, Carvalho L, Chen W, Ben-Chetrit E, Chams-Davatchi C, Correia J, Crespo J, Dias C, Dong Y, Paixao Duarte F, Elmuntaser K, Elonakov AV, Grana Gil J, Haghdoost AA, Hayani RM, Houman H, Isayeva AR, Jamshidi AR, Kaklamanis P, Kumar A, Kyrgidis A, Madanat W, Nadji A, Namba K, Ohno S, Olivieri I, Vaz Patto J, Pipitone N, de Queiroz MV, Ramos F, Resende C, Rosa CM, Salvarani C, Serra MJ, Shahram F, Shams H, Sharquie KE, Sliti-Khanfir M, Tribolet de Abreu T, Vasconcelos C, Vedes J, Wechsler B, Cheng YK, Zhang Z, Ziaei N. 2014. The International Criteria for Behcet’s Disease (ITR-ICBD). The International Criteria for Behcet’s Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol, 28: 338-347.
De Smet MD, Dayan M. 2000. Prospective determination of T-cell responses to S-antigen in Behcet’s disease patients and controls. Invest Ophthalmol Vis Sci, 41: 3480-3484.
Doğan P, Tanrikulu G, Soyuer Ü, Köse K. 1994. Oxidative enzymes of polymorphonuclear leucocytes and plasma fibrinogen, ceruloplasmin, and copper levels in Behcet's disease. Clin Biochem, 27: 413-418.
Ebru U, Burak U, Yusuf S, Reyhan B, Arif K, Faruk TH, Emin M, Aydin K, Atilla II, Semsettin S, Kemal E. 2008. Cardioprotective effects of Nigella sativa oil on cyclosporine A‐induced cardiotoxicity in rats. Basic Clin Pharmacol Toxicol, 103: 574-580.
El-Mahmoudy A, Matsuyama H, Borgan MA, Shimizu Y, El-Sayed MG, Minamoto N, Takewaki T. 2002. Thymoquinone suppresses expression of inducible nitric oxide synthase in rat macrophages. Int immunopharmacol, 2: 1603-1611.
Gaweł S, Wardas M, Niedworok E, Wardas P. 2004. Malondialdehyde (MDA) as a lipid peroxidation marker. Wiad Lek, 57: 453-455.
Gheita TA, Kenawy SA. 2012. Effectiveness of Nigella sativa oil in the management of rheumatoid arthritis patients: A placebo controlled study. Phytother Res, 26: 1246-1248.
Hadi V, Kheirouri S, Alizadeh M, Khabbazi A, Hosseini H. 2016. Effects of Nigella sativa oil extract on inflammatory cytokine response and oxidative stress status in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled clinical trial. Avicenna J Phytomed, 6: 34-43.
Harzallah O, Kerkeni A, Baati T, Mahjoub S. 2008. Oxidative stress: correlation with Behcet’s disease duration, activity and severity. Eur J Intern Med, 19: 541-547.
Hosseini A, Shanehbandi D, Estiar MA, Gholizadeh S, Khabbazi A, Khodadadi H, Sakhinia E, Babaloo Z. 2015. A single nucleotide polymorphism in the FOXP3 gene associated with Behcet’s disease in an Iranian population. Clin Lab, 61(12):1897-903.
Houghton PJ, Zarka R, de las Heras B, Hoult JR. 1995. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta med, 61: 33-36.
Khabbazi A, Ghojazadeh M, Hajebrahimi S, Nikniaz Z. 2019. Relationship between vitamin D level and Bechet’s disease activity: A systematic review and meta-analysis. Int J Vitam Nutr Res, 21: 1-8.
Köse K, Doğan P, Aşçioğlu M, Erkiliç K, Aşçioğlu O. 1995. Oxidative stress and antioxidant defenses in plasma of patients with Behcet’s disease. Tohoku J Exp Med, 176: 239-248.
Mahdavi R, Namazi N, Alizadeh M, Farajnia S. 2016. Nigella sativa oil with a calorie-restricted diet can improve biomarkers of systemic inflammation in obese women: A randomized double-blind, placebo-controlled clinical trial. J Clin Lipidol, 10: 1203-1211.
Majdalawieh AF, Hmaidan R, Carr RI. 2010. Nigella sativa modulates splenocyte proliferation, Th1/Th2 cytokine profile, macrophage function and NK anti-tumor activity. J Ethnopharmacol, 131: 268-275.
Mansour M, Tornhamre S. 2004. Inhibition of 5-lipoxygenase and leukotriene C4 synthase in human blood cells by thymoquinone. J Enzyme Inhib Med Chem, 19: 431-436.
Mantaş C, Direskeneli H, Ekşioglu-Demiralp E, Akoglu T. 1999. Serum levels of Th2 cytokines IL-4 and IL-10 in Behcet's disease. J Rheumatol, 26: 510-512.
Mazzoccoli G, Matarangolo A, Rubino R, Inglese M, De Cata A. 2016. Behcet syndrome: from pathogenesis to novel therapies. Clin Exp Med, 16: 1-12.
Miller NJ, Rice-Evans C, Davies MJ, Gopinathan V, Milner A. 1993. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci (Lond), 84: 407-412.
Najim RA, Sharquie KE, Abu-Raghif AR. 2007. Oxidative stress in patients with Behcet's disease: I correlation with severity and clinical parameters. J Dermatol, 34: 308-314.
Nielsen F, Mikkelsen BB, Nielsen JB, Andersen HR, Grandjean P. 1997. Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Oxid Med Cell Longev, 43: 1209-1214.
Sayed-Ahmed MM, Aleisa AM, Al-Rejaie SS, Al-Yahya AA, Al-Shabanah OA, Hafez MM, Nagi MN. 2010. Thymoquinone attenuates diethylnitrosamine induction of hepatic carcinogenesis through antioxidant signaling. Oxid Med Cell Longev, 3: 254-261.
Schleicher P, Saleh M. 2000. Black cumin: the magical Egyptian herb for allergies, asthma, and immune disorders. Inner Traditions/Bear & Co.
Sethi G, Ahn KS, Aggarwal BB. 2008. Targeting nuclear factor-κB activation pathway by thymoquinone: role in suppression of antiapoptotic gene products and enhancement of apoptosis. Mol Cancer Res, 6: 1059-1070.
Sharifian A, Farahani S, Pasalar P, Gharavi M, Aminian O. 2005. Shift work as an oxidative stressor. J Circadian Rhythms, 3: 15.
Takeno M, Kariyone A, Yamashita N, Takiguchi M, Mizushima Y, Kaneoka H, Sakane T. 1995. Excessive function of peripheral blood neutrophils from patients with behcet's disease and from hla‐b51 transgenic mice. Arthritis Rheum, 38: 426-433.
Tekeoglu I, Dogan A, Ediz L, Budancamanak M, Demirel A. 2007. Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat models. Phytother Res, 21: 895-897.
Turan B, Pfister K, Diener PA, Hell M, Möller B, Boyvat A, Ergin S, Villiger PM. 2008. Soluble tumour necrosis factor receptors sTNFR1 and sTNFR2 are produced at sites of inflammation and are markers of arthritis activity in Behcet’s disease. Scand J Rheumatol, 37: 135-141.
Umar S, Zargan J, Umar K, Ahmad S, Katiyar CK, Khan HA. 2012. Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats. Chem Biol Interact, 197: 40-46.
Vaillancourt F, Silva P, Shi Q, Fahmi H, Fernandes JC, Benderdour M. 2011. Elucidation of molecular mechanisms underlying the protective effects of thymoquinone against rheumatoid arthritis. J Cell Biochem, 112: 107-117.
Yamamoto JH, Minami M, Inaba G, Masuda K, Mochizuki M. 1993. Cellular autoimmunity to retinal specific antigens in patients with Behcet's disease. Br J Ophthalmol, 77: 584-589.
Yoruk O, Gur F, Uyanik H, Yasar M, Mutlu V, Altas E, Baysal E, Taysi S. 2010. Antioxidant effects of Nigella sativa in the treatment of experimentally induced rhinosinusitis. Macedonian J Med Sci, 3: 132-137.