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

Document Type : Original Research Article


1 Department of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran

2 Department of Internal Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

3 Department of Agriculture, Barij Essence Pharmaceutical Company, Kashan, Iran


Objectives: Nigella sativa is a medicinal plant that has long been used in traditional medicine for treating various conditions. Numerous animal studies provided evidences that the seed may elicit a broad anti-inflammatory/anti-oxidant activity. The aim of the present clinical trial was to evaluate anti-inflammatory and antioxidant properties of Nigella sativa oil in patients with rheumatoid arthritis (RA).
Materials and Methods: Forty-two patients with RA were assigned into two groups in this randomized, double blind, placebo-controlled clinical trial. Subjects in intervention group received two capsules, 500 mg each, of Nigella sativa oil, each day for 8 weeks. The other group consumed two capsules as placebo per day for the same period of time. Serum TNF-α, IL-10, and whole blood levels of oxidative stress parameters were measured at baseline and end of the trial.
Results: The serum level of IL-10 was increased in the Nigella sativa group (p<0.01). Moreover, treatment with Nigella sativa led to significant reduction of serum MDA and NO compared with baseline (p<0.05). There were no significant differences in the TNF-α, SOD, catalase, and TAS values between or within the groups, before and after the intervention (p>0.05).
Conclusions: This study indicates that Nigella sativa could improve inflammation and reduce oxidative stress in patients with RA. It is suggested that Nigella sativa may be a beneficial adjunct therapy in this population of patients


Main Subjects

Doyle TJ, Lee JS, Dellaripa PF, Lederer JA, Matteson EL, Fischer A, Ascherman DP, Glassberg MK, Ryu JH, Danoff SK, Brown KK, Collard HR, Rosas IO. 2014. A roadmap to promote clinical and translationalresearch in rheumatoid arthritis-associated interstitial lung disease. Chest, 145: 454-463.
Zyrianova Y, Kelly BD, Gallagher C, McCarthy C, Molloy MG, Sheehan J, Dinan TG. 2006. Depression and anxiety in rheumatoid arthritis: the role of perceived social support. Ir J Med Sci, 175: 32-36.
Goronzy JJ, Weyand CM. 2009. Developments in the scientific understanding of rheumatoid arthritis. Arthritis Res Ther, 11:249.
Weyand CM, Goronzy JJ, Takemura S, Kurtin PJ. 2000. Cell-cell interactions in synovitis. Interactions between T cells and B cells in rheumatoid arthritis. Arthritis Res, 2: 457-463.
El Gazzar MA, El Mezayen R, Nicolls MR, Dreskin SC. 2007. Thymoquinone attenuates proinflammatory responses in lipopolysaccharide-activated mast cells by modulating NF-kappaB nuclear transactivation. Biochim Biophys Acta, 1770: 556-564.
Yudoh K, Matsuno H, Nakazawa F, Yonezawa T, Kimura T. 2000. Reduced expression of the regulatory CD4+ T cell subset is related to Th1/Th2 balance and disease severity in rheumatoid arthritis. Arthritis Rheum, 43: 617-627.
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.
Wadley AJ, Veldhuijzen van Zanten JJ, Stavropoulos-Kalinoglou A, Metsios GS, Smith JP, Kitas GD, Aldred S.. 2014. Three months of moderate-intensity exercise reduced plasma 3-nitrotyrosine in rheumatoid arthritis patients. Eur J Appl Physiol, 114: 1483-1492.
Kurien BT, Scofield RH. 2003. Free radical mediated peroxidative damage in systemic lupus erythematosus. Life Sci, 73: 1655-1666.
Amin, G. R. 1991. Popular medicinal plants of Iran, Iranian Research Institute of Medicinal Plants Tehran.
Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F. 2013. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed, 3: 337-352.
El-Mahmoudy A, Shimizu Y, Shiina T, Matsuyama H, Nikami H, Takewaki T. 2005. Macrophage-derived cytokine and nitric oxide profiles in type I and type II diabetes mellitus: effect of thymoquinone. Acta Diabetol, 42: 23-30.
Toubi E, Kessel A, Mahmudov Z, Hallas K, Rozenbaum M, Rosner I. 2005. Increased spontaneous apoptosis of CD4+ CD25+ T cells in patients with active rheumatoid arthritis is reduced by infliximab. Ann N Y Acad Sci, 1051: 506-514.
Gheita, T. A. and S. A. Kenawy. 2012. "Effectiveness of Nigella sativa oil in the management of rheumatoid arthritis patients: a placebo controlled study." Phytother Res, 26: 1246-1248.
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.
Aebi H. 1984. Catalase in vitro. Methods Enzymol, 105: 121-6.
Moshage H, Kok B, Huizenga JR, Jansen PL. 1995. Nitrite and nitrate determinations in plasma: a critical evaluation. Clin Chem, 41: 892-896.
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.
Katsoulis K, Kontakiotis T, Leonardopoulos I, Kotsovili A, Legakis IN, Patakas D. 2003. Serum total antioxidant status in severe exacerbation of asthma: correlation with the severity of the disease. J Asthma, 40: 847-854.
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.
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.
Tekeoglu, I., A. Dogan, L. Ediz, M. Budancamanak and A. Demirel. 2007. "Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat models." Phytother Res, 21: 895-897.
Schett G, Stach C, Zwerina J, Voll R, Manger B. 2008. How antirheumatic drugs protect joints from damage in rheumatoid arthritis. Arthritis Rheum, 58: 2936-2948.
Williams RO. 2004. Collagen-induced arthritis as a model for rheumatoid arthritis. Methods Mol Med, 98: 207-216.
Juarranz Y, Abad C, Martinez C, Arranz A, Gutierrez-Canas I, Rosignoli F, Gomariz RP, Leceta J. 2005. Protective effect of vasoactive intestinal peptide on bone destruction in the collagen-induced arthritis model of rheumatoid arthritis. Arthritis Res Ther, 7: R1034-1045.
Majdalawieh AF, Carr RI. 2010. In vitro investigation of the potential immunomodulatory and anti-cancer activities of black pepper (Piper nigrum) and cardamom (Elettaria cardamomum). J Med Food, 13: 371-381.
Wu CH, Lin MC, Wang HC, Yang MY, Jou MJ, Wang CJ. 2011. Rutin inhibits oleic acid induced lipid accumulation via reducing lipogenesis and oxidative stress in hepatocarcinoma cells. J Food Sci, 76: T65-72.
Schulz JB, Lindenau J, Seyfried J, Dichgans J. 2000. Glutathione, oxidative stress and neurodegeneration. Eur J Biochem, 267: 4904-4911.
Seo WG, Pae HO, Oh GS, Chai KY, Kwon TO, Yun YG, Kim NY, Chung HT. 2001. Inhibitory effects of methanol extract of Cyperus rotundus rhizomes on nitric oxide and superoxide productions by murine macrophage cell line, RAW 264.7 cells. J Ethnopharmacol, 76: 59-64.
Blanco FJ, Ochs RL, Schwarz H, Lotz M. 1995. Chondrocyte apoptosis induced by nitric oxide. Am J Pathol, 146: 75-85.
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.
Sayed-Ahmed, M. M., A. M. Aleisa, S. S. Al-Rejaie, A. A. Al-Yahya, O. A. Al-Shabanah, M. M. Hafez and M. N. Nagi. 2010. "Thymoquinone attenuates diethylnitrosamine induction of hepatic carcinogenesis through antioxidant signaling." Oxid Med Cell Longev, 3: 254-261.
Hassan, A. S., J. H. Ahmed and S. S. Al-Haroon. 2012. A study of the effect of Nigella sativa (Black seeds) in isoniazid (INH)- induced hepatotoxicity in rabbits. Indian J Pharmacol, 44: 678-682
Seif, A. A. 2014. "Nigella Sativa reverses osteoporosis in ovariectomized rats."BMC Complement Altern Med, 14: 22.
Wilkins R, Tucci M, Benghuzzi H. 2011. Role of plant-derived antioxidants on NF-kb expression in LPS-stimulated macrophages - biomed. Biomed Sci Instrum, 47: 222-227.
El Gazzar MA, El Mezayen R, Nicolls MR, Dreskin SC. 2007. Thymoquinone attenuates proinflammatory responses in lipopolysaccharide-activated mast cells by modulating NF-kappaB nuclear transactivation. Biochim Biophys Acta, 1770: 556-564.
Ahn K, Aggarwal B. 2005. Transcription Factor NF-κB : A Sensor for Smoke and Stress Signals. Ann N Y Acad Sci, 1056: 218-233.
Ishibashi T. 2013. Molecular Hydrogen: New Antioxidant and Anti-inflammatory Therapy for Rheumatoid Arthritis and Related Diseases. Curr Pharm Des, 19: 6375-6381
Woo CC, Kumar AP, Sethi G, Tan KH. 2012. Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol, 83: 443-451.