Nigella sativa: Valuable perspective in the management of chronic diseases

Document Type: Review Article


1 Iuliu Hatieganu University of Medicine and Pharmacy, Department of Pharmacology, Toxicology and Clinical Pharmacology, Cluj Napoca, Romania

2 Iuliu Hatieganu University of Medicine and Pharmacy, Department of Genetics, Cluj Napoca, Romania

3 University of Salerno, Department of Pharmacy, Fisciano, Salerno, Italy

4 Research Station for Viticulture and Enology Blaj, Blaj, Romania


Objective(s): Over the past 20 years, increasing interest in the use of medicinal plants as alternative or adjuvant treatments of several chronic diseases was observed. Accordingly, Nigella sativa or black cumin, a medicinal plant rich in bioactive compounds, has been used worldwide for food purposes or in traditional medicines. This paper aims to reveal N. sativa potential as adjunct treatment in cardiovascular diseases, diabetes, and hematological malignancies, due to their increasing prevalence and difficult management in everyday life.
Materials and Methods: Databases like PubMed, Web of Science, Science Direct, Scopus, and Google Scholar were used to search the literature data. Keywords like anti-inflammatory effect, anti-oxidant effect, antihypertensive effects, hypolipidemic effects and hematological malignancies were used in combination with  N. sativa.
Results: Because of its numerous pharmacological actions, but especially for its anti-oxidant and anti-inflammatory properties, in vivo and in vitro studies demonstrated N. sativa positive effect against diabetes, hypertension, and hypercholesterolemia, all of them associated to cardiovascular diseases progression. Also, it was proved to have marked anti-proliferative, cytotoxic, pro-apoptotic, and anti-metastatic effects, in both solid cancers and hematological malignancies.
Conclusion: N. sativa used as complementary treatment to classical medications can improve the management of several chronic diseases


1. Pop RM, Puia IC, Puia A, Chedea VS, Leopold N, Bocsan IC, et al. Characterization of Trametes versicolor: Medicinal Mushroom with Important Health Benefits. Not Bot Horti Agrobot Cluj-Napoca 2018; 46:343–349.
2. Zavoi S, Fetea F, Ranga F, Pop RM, Baciu A, Socaciu C. Comparative Fingerprint and Extraction Yield of Medicinal Herb Phenolics with Hepatoprotective Potential, as Determined by UV-Vis and FT-MIR Spectroscopy. Not Bot Horti Agrobot Cluj-Napoca 2011; 39:82–89.
3. Mocan A, Pop RM, Bocsan CI, Echeverría J, Buzoianu AD, Neag MA, et al. Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders. Front Pharmacol 2018; 9:1–30.
4. Akram KM, Afzal M. Chemical composition of Nigella sativa Linn: Part 2 Recent advances. Inflammopharmacology 2016; 24:67–79.
5. Gharby S, Harhar H, Guillaume D, Roudani A, Boulbaroud S, Ibrahimi M, et al. Chemical investigation of Nigella sativa L. seed oil produced in Morocco. J Saudi Soc Agric Sci 2015; 14:172–177.
6. Sturtevant EL, Hedrick UP. Sturtevant’s edible plants of the world. Dover Publications; 1972.
7. Atta BM. Some characteristics of nigella (Nigella sativa L.) seed cultivated in Egypt and its lipid profile. Food Chem 2003; 83:63–68.
8. Cheikh-Rouhou S, Besbes S, Lognay G, Blecker C, Deroanne C, Attia H. Sterol composition of black cumin (Nigella sativa L.) and Aleppo pine (Pinus halepensis Mill.) seed oils. J Food Compos Anal 2008; 21:162–168.
9. D’Antuono LF, Moretti A, Lovato AFS. Seed yield, yield components, oil content and essential oil content and composition of Nigella sativa L. and Nigella damascena L. Ind Crop Prod 2002; 15:59–69.
10. Kiralan M, Özkan G, Bayrak A, Ramadan MF. Physicochemical properties and stability of black cumin (Nigella sativa) seed oil as affected by different extraction methods. Ind Crops Prod 2014; 57:52–58.
11. Maulidiani M, Sheikh BY, Mediani A, Wei LS, Ismail IS, Abas F, et al. Differentiation of Nigella sativa seeds from four different origins and their bioactivity correlations based on NMR-metabolomics approach. Phytochem Lett 2015; 13:308–318.
12. Pop RM, Militaru C, Chedea VS. Phytochemicals of Nigella sativa: Structure, Detection and Conditioning. In: Pop RM, editor. Future Perspectives on Nigella Sativa: Characterization and Pharmacological Properties. Nova Science Publishers, Inc.; 2018; 1–46.
13. Tariq M. Nigella sativa seeds: folklore treatment in modern day medicine. Saudi J Gastroenterol 2008; 14:105–6.
14. Neag M, Bocşan CI, Crăciun CI, Catinean A. Nigella sativa, Microbiota and Gastro-Intestinal Cancer. In: Pop RM, editor. Future Perspectives on Nigella Sativa: Characterization and Pharmacological Properties. Nova Science Publishers, Inc.; 2018; 197–218.
15. Mousavi SM, Sheikhi A, Varkaneh HK, Zarezadeh M, Rahmani J, Milajerdi A. Effect of Nigella sativa supplementation on obesity indices: A systematic review and meta-analysis of randomized controlled trials. Complement Ther Med 2018; 38:48–57.
16. Bocşan CI, Neag M, Zdrenghea MT, Buzoianu AD. Anti-Inflammatory, Immunomodulatory and Antiallergic Effects of Nigella sativa. In: Pop RM, editor. Future Perspectives on Nigella Sativa: Characterization and Pharmacological Properties. Nova Science Publishers, Inc.; 2018; 103–148.
17. Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed 2013; 3:337–352.
18. Ait Mbarek L, Ait Mouse H, Elabbadi N, Bensalah M, Gamouh A, Aboufatima R, et al. Anti-tumor properties of blackseed (Nigella sativa L.) extracts. Brazilian J Med Biol Res = Rev Bras Pesqui medicas e Biol 2007; 40:839–47.
19. Gilani AH, Aziz N, Khurram IM, Chaudhary KS, Iqbal A. Bronchodilator, spasmolytic and calcium antagonist activities of Nigella sativa seeds (Kalonji): a traditional herbal product with multiple medicinal uses. J Pak Med Assoc 2001; 51:115–20.
20. Khan SU, Khan RA, Khan WU. Phytochemical screening and in vitro antioxidant activities of methanolic extract of nigella sativa seeds. World Appl Sci J 2017; 35:971–975.
21. Khan SA, Khan AM, Karim S, Kamal MA, Damanhouri GA, Mirza Z. Panacea seed ‘Nigella’: A review focusing on regenerative effects for gastric ailments. Saudi J Biol Sci 2016; 23:542–553.
22. Chedea VS, Pop RM, Rotar MC. Nigella sativa Bioactive Components: Key Aspects of Pharmacological Effects. In: Pop RM, editor. Future Perspectives on Nigella Sativa: Characterization and Pharmacological Properties. Nova Science Publishers, Inc.; 2018; 47–78.
23. Amin B, Hosseinzadeh H. Black Cumin (Nigella sativa) and Its Active Constituent, Thymoquinone: An Overview on the Analgesic and Anti-inflammatory Effects. Planta Med 2016; 82:8–16.
24. Oskouei Z, Akaberi M, Hosseinzadeh H. A glance at black cumin (Nigella sativa) and its active constituent, thymoquinone, in ischemia: a review. Mashhad Univ Med Sci 2018; 21:1200–1209.
25. Tavakkoli A, Mahdian V, Razavi BM, Hosseinzadeh H. Review on Clinical Trials of Black Seed (Nigella sativa ) and Its Active Constituent, Thymoquinone. J pharmacopuncture 2017; 20:179–193.
26. Gholamnezhad Z, Havakhah S, Boskabady MH. Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review. J Ethnopharmacol 2016; 190:372–386.
27. Wajs A, Bonikowski R, Kalemba D. Composition of essential oil from seeds of Nigella sativa L. cultivated in Poland. Flavour Fragr J 2008; 23:126–132.
28. Atta-ur-Rahman, Malik S, Hasan SS, Choudhary MI, Ni CZ, Clardy J. Nigellidine — A new indazole alkaloid from the seeds of Nigella sativa. Tetrahedron Lett 1995; 36:1993–1996.
29. Mehta BK, Mehta P, Gupta M. A new naturally acetylated triterpene saponin from Nigella sativa. Carbohydr Res 2009; 344:149–151.
30. Mehta BK, Pandit V, Gupta M. New principles from seeds of Nigella sativa. Nat Prod Res 2009; 23:138–148.
31. Boskabady MH, Mohsenpoor N, Takaloo L. Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomedicine 2010; 17:707–713.
32. Mollazadeh H, Afshari AR, Hosseinzadeh H. Review on the Potential Therapeutic Roles of Nigella sativa in the Treatment of Patients with Cancer: Involvement of Apoptosis: - Black cumin and cancer. J pharmacopuncture 2017; 20:158–172.
33. Dubey PN, Singh B, Mishra BK, Kant K, Solanki RK. Nigella (Nigella sativa): A high value seed spice with immense medicinal potential. Indian J Agric Sci 2016; 86:967–979.
34. Gholamnezhad Z, Keyhanmanesh R, Boskabady MH. Anti-inflammatory, antioxidant, and immunomodulatory aspects of Nigella sativa for its preventive and bronchodilatory effects on obstructive respiratory diseases: A review of basic and clinical evidence. J Funct Foods 2015; 17:910–927.
35. Mariod AA, Ibrahim RM, Ismail M, Ismail N. Antioxidant activity and phenolic content of phenolic rich fractions obtained from black cumin (Nigella sativa) seedcake. Food Chem 2009; 116:306–312.
36. Periasamy VS, Athinarayanan J, Alshatwi AA. Anticancer activity of an ultrasonic nanoemulsion formulation of Nigella sativa L. essential oil on human breast cancer cells. Ultrason Sonochem 2016; 31:449–455.
37. Le PM, Benhaddou-Andaloussi A, Elimadi A, Settaf A, Cherrah Y, Haddad PS. The petroleum ether extract of Nigella sativa exerts lipid-lowering and insulin-sensitizing actions in the rat. J Ethnopharmacol 2004; 94:251–259.
38. Asgary S, Ghannadi A, Dashti G, Helalat A, Sahebkar A, Najafi S. Nigella sativa L. improves lipid profile and prevents atherosclerosis: Evidence from an experimental study on hypercholesterolemic rabbits. J Funct Foods 2013; 5:228–234.
39. Kooti W, Hasanzadeh-Noohi Z, Sharafi-Ahvazi N, Asadi-Samani M, Ashtary-Larky D. Phytochemistry, pharmacology, and therapeutic uses of black seed (Nigella sativa). Chin J Nat Med 2016; 14:732–745.
40. Rafati S, Niakan M, Naseri M. Anti-microbial effect of Nigella sativa seed extract against staphylococcal skin Infection. Med J Islam Repub Iran 2014; 28:42.
41. Forouzanfar F, Bazzaz BSF, Hosseinzadeh H. Black cumin (Nigella sativa) and its constituent (thymoquinone): a review on antimicrobial effects. Iran J Basic Med Sci 2014; 17:929–38.
42. Hosseinzadeh H, Parvardeh S. Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. Phytomedicine 2004; 11:56–64.
43. Bepari A, Parashivamurthy M, Niazi S. Evaluation of anticonvulsant activity of volatile oil extract of Nigella sativa seeds by chemically induced seizure model in albino rats. Int J Basic Clin Pharmacol 2016; 5:1300–1307.
44. Bashir MU, Qureshi HJ. Analgesic effect of Nigella sativa seeds extract on experimentally induced pain in albino mice. J Coll Physicians Surg Pak 2010; 20:464–7.
45. Parvardeh S, Sabetkasaei M, Moghimi M, Masoudi A, Ghafghazi S, Mahboobifard F. Role of L-arginine/NO/cGMP/KATP channel signaling pathway in the central and peripheral antinociceptive effect of thymoquinone in rats. Iran J Basic Med Sci 2018; 21:625–633.
46. Tavakkoli A, Ahmadi A, Razavi BM, Hosseinzadeh H. Black Seed (Nigella Sativa) and its Constituent Thymoquinone as an Antidote or a Protective Agent Against Natural or Chemical Toxicities. Iran J Pharm Res  IJPR 2017; 16:2–23.
47. Hosseini SM, Taghiabadi E, Abnous K, Hariri AT, Pourbakhsh H, Hosseinzadeh H. Protective effect of thymoquinone, the active constituent of Nigella sativa fixed oil, against ethanol toxicity in rats. Iran J Basic Med Sci 2017; 20:927–939.
48. Harzallah JH, Kouidhi B, Flamini G, Bakhrouf A, Mahjoub T, Jrah Harzallah H, et al. Chemical composition, antimicrobial potential against cariogenic bacteria and cytotoxic activity of Tunisian Nigella sativa essential oil and thymoquinone. Food Chem 2011; 129:1469–1474.
49. Mohamadin AM, Sheikh B, Abd El-Aal AA, Elberry AA, Al-Abbasi FA. Protective effects of Nigella sativa oil on propoxur-induced toxicity and oxidative stress in rat brain regions. Pestic Biochem Physiol 2010; 98:128–134.
50. Aljabre SHM, Alakloby OM, Randhawa MA. Dermatological effects of Nigella sativa. J Dermatology Dermatologic Surg 2015; 19:92–98.
51. Boca AN. The Benefits of Nigella sativa in Various Skin Conditions. In: Pop RM, editor. Future Perspectives on Nigella Sativa: Characterization and Pharmacological Properties. Nova Science Publishers, Inc.; 2018; 219–240.
52. Razavi BM, Hosseinzadeh H. A review of the effects of Nigella sativa L. and its constituent, thymoquinone, in metabolic syndrome. J Endocrinol Invest 2014; 37:1031–1040.
53. Hadi V, Kheirouri S, Alizadeh M, Khabbazi A, Hosseini H. 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 phytomedicine 2016; 6:34–43.
54. Meddah B, Ducroc R, El Abbes Faouzi M, Eto B, Mahraoui L, Benhaddou-Andaloussi A, et al. Nigella sativa inhibits intestinal glucose absorption and improves glucose tolerance in rats. J Ethnopharmacol 2009; 121:419–424.
55. Halliwell B, Gutteridge JM. The importance of free radicals and catalytic metal ions in human diseases. Mol Aspects Med 1985; 8:89–193.
56. Halliwell B, Houltt JR, Blaket DR. Oxidants, inflammation, and anti-inflammatory drugs. Fed Am Soc Exp Biol J 1988; 2:2867–2873.
57. Stadtman ER. Role of Oxidant Species in Aging. Curr Med Chem 2004; 11:1105–1112.
58. Mollazadeh H, Mahdian D, Hosseinzadeh H. Medicinal plants in treatment of hypertriglyceridemia: A review based on their mechanisms and effectiveness. 2018; 53:43–52.
59. Entok E, Ustuner MC, Ozbayer C, Tekin N, Akyuz F, Yangi B, et al. Anti-inflammatuar and anti-oxidative effects of Nigella sativa L.: 18FDG-PET imaging of inflammation. Mol Biol Rep 2014; 41:2827–2834.
60. Balbaa M, Abdulmalek SA, Khalil S. Oxidative stress and expression of insulin signaling proteins in the brain of diabetic rats: Role of Nigella sativa oil and antidiabetic drugs. Holscher C, editor. PLoS One 2017; 12:e0172429.
61. Noor NA, Fahmy HM, Mohammed FF, Elsayed AA, Radwan NM. Nigella sativa amliorates inflammation and demyelination in the experimental autoimmune encephalomyelitis-induced Wistar rats. Int J Clin Exp Pathol 2015; 8:6269–86.
62. Yildiz A, Balikci E. Antimicrobial, anti-inflammatory and antioxidant activity of Nigella sativa in clinically endometritic cows. J Appl Anim Res 2016; 44:431–435.
63. Norouzi F, Abareshi A, Asgharzadeh F, Beheshti F, Hosseini M, Farzadnia M, et al. The effect of Nigella sativa on inflammation-induced myocardial fibrosis in male rats. Res Pharm Sci 2017; 12:74–81.
64. Schiotis RE, Goşa D. Nigella sativa as an Adjunctive Therapy for Rheumatic Diseases. In: Pop RM, editor. Future Perspectives on Nigella Sativa: Characterization and Pharmacological Properties. Nova Science Publishers, Inc.; 2018; 149–180.
65. Umar S, Zargan J, Umar K, Ahmad S, Katiyar CK, Khan HA. Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats. Chem Biol Interact 2012; 197:40–46.
66. Hossen MJ, Yang WS, Kim D, Aravinthan A, Kim JH, Cho JY. Thymoquinone: An IRAK1 inhibitor with in vivo and in vitro anti-inflammatory activities. Sci Rep 2017; 7:42995.
67. Reddy KS. Cardiovascular diseases in the developing countries: dimensions, determinants, dynamics and directions for public health action. Public Health Nutr 2002; 5:231–237.
68. Prabhakaran D, Jeemon P, Roy A. Cardiovascular Diseases in India: Current Epidemiology and Future Directions. Circulation 2016; 133:1605–20.
69. Rahman K, Lowe GM. Garlic and cardiovascular disease: a critical review. J Nutr 2006; 136:736S–740S.
70. Cave AC, Brewer AC, Narayanapanicker A, Ray R, Grieve DJ, Walker S, et al. NADPH Oxidases in Cardiovascular Health and Disease. Antioxid Redox Signal 2006; 8:691–728.
71. Leong XF, Rais MM, Jaarin K. Nigella sativa and Its Protective Role in Oxidative Stress and Hypertension. Evid Based Complement Alternat Med 2013; 2013:120732.
72. Sahebkar A, Beccuti G, Simental-Mendía LE, Nobili V, Bo S. Nigella sativa (black seed) effects on plasma lipid concentrations in humans: A systematic review and meta-analysis of randomized placebo-controlled trials. Pharmacol Res 2016; 106:37–50.
73. Szentandrássy N, Szigeti G, Szegedi C, Sárközi S, Magyar J, Bányász T, et al. Effect of thymol on calcium handling in mammalian ventricular myocardium. Life Sci 2004; 74:909–21.
74. Zaoui A, Cherrah Y, Lacaille-Dubois MA, Settaf A, Amarouch H, Hassar M. Diuretic and hypotensive effects of Nigella sativa in the spontaneously hypertensive rat. Therapie 2000; 55:379–82.
75. Jaarin K, Foong WD, Yeoh MH, Kamarul ZYN, Qodriyah HMS, Azman A, et al. Mechanisms of the antihypertensive effects of Nigella sativa oil in L-NAME-induced hypertensive rats. Clinics (Sao Paulo) 2015; 70:751–7.
76. Guzik TJ, West NEJ, Pillai R, Taggart DP, Channon KM. Nitric oxide modulates superoxide release and peroxynitrite formation in human blood vessels. Hypertension 2002; 39:1088–1094.
77. Cracowski JL, Degano B, Chabot F, Labarère J, Schwedhelm E, Monneret D, et al. Independent Association of Urinary F2 - Isoprostanes With Survival in Pulmonary Arterial Hypertension. Chest 2012; 142:869–876.
78. Landmesser U, Dikalov S, Price SR, McCann L, Fukai T, Holland SM, et al. Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest 2003; 111:1201–9.
79. Zalba G, José GS, Moreno MU, Fortuño MA, Fortuño A, Beaumont FJ, et al. Oxidative Stress in Arterial Hypertension. Hypertension 2001; 38:1395–1399.
80. Shafiq H, Ahmad A, Masud T, Kaleem M. Cardio-protective and anti-cancer therapeutic potential of Nigella sativa. Iran J Basic Med Sci 2014; 17:967–980.
81. Nader MA, El-Agamy DS, Suddek GM. Protective effects of propolis and thymoquinone on development of atherosclerosis in cholesterol-fed rabbits. Arch Pharm Res 2010; 33:637–643.
82. Sabzghabaee AM, Dianatkhah M, Sarrafzadegan N, Asgary S, Ghannadi A. Clinical evaluation of Nigella sativa seeds for the treatment of hyperlipidemia: a randomized, placebo controlled clinical trial. Med Arch (Sarajevo, Bosnia Herzegovina) 2012; 66:198–200.
83. Bhatti I, Rehman F, Khan M, Marwat S. Effect of prophetic medicine kalonji (Nigella sativa L.) on lipid profile of human beings. An in vivo approach. World Appl Sci J 2009; 6:1053–1057.
84. Ibrahim RM, Hamdan NS, Ismail M, Saini SM, Abd Rashid SN, Abd Latiff L, et al. Protective Effects of Nigella sativa on Metabolic Syndrome in Menopausal Women. Adv Pharm Bull 2014; 4:29–33.
85. Alobaidi AAH. Effect of Nigella Sativa and Allium Sativum Coadminstered with Simvastatin in Dyslipidemia Patients: A Prospective, Randomized, Double-Blind Trial. Antiinflamm Antiallergy Agents Med Chem 2014; 13:68–74.
86. de Jong A, Plat J, Mensink RP. Metabolic effects of plant sterols and stanols (Review). J Nutr Biochem 2003; 14:362–369.
87. Bamosa AO, Ali BA, al-Hawsawi ZA. The effect of thymoquinone on blood lipids in rats. Indian J Physiol Pharmacol 2002; 46:195–201.
88. Kanter M, Coskun O, Budancamanak M. Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World J Gastroenterol 2005; 11:6684.
89. Liu H, Liu HY, Jiang YN, Li N. Protective effect of thymoquinone improves cardiovascular function, and attenuates oxidative stress, inflammation and apoptosis by mediating the PI3K/Akt pathway in diabetic rats. Mol Med Rep 2016; 13:2836–2842.
90. Shabana A, El-Menyar A, Asim M, Al-Azzeh H, Al Thani H. Cardiovascular Benefits of Black Cumin (Nigella sativa). Cardiovasc Toxicol 2013; 13:9–21.
91. Ragheb A, Elbarbry F, Prasad K, Mohamed A, Ahmed MS, Shoker A. Attenuation of the development of hypercholesterolemic atherosclerosis by thymoquinone. Int J Angiol 2008; 17:186–92.
92. Kaatabi H, Bamosa AO, Badar A, Al-Elq A, Abou-Hozaifa B, Lebda F, et al. Nigella sativa improves glycemic control and ameliorates oxidative stress in patients with type 2 diabetes mellitus: Placebo controlled participant blinded clinical trial. PLoS One 2015; 10:1–15.
93. Hosseini SM, Taghiabadi E, Abnous K, Hariri AT, Pourbakhsh H. Protective effect of thymoquinone, the active constituent of Nigella sativa fixed oil, against ethanol toxicity in rats. Iran J Basic Med Sci 2017; 20:927–939.
94. Rchid H, Chevassus H, Nmila R, Guiral C, Petit P, Chokairi M, et al. Nigella sativa seed extracts enhance glucose-induced insulin release from rat-isolated Langerhans islets. Fundam Clin Pharmacol 2004; 18:525–529.
95. Benhaddou-Andaloussi A, Martineau L, Spoor D, Vuong T, Leduc C, Joly E, et al. Antidiabetic Activity of Nigella sativa. Seed Extract in Cultured Pancreatic β-cells, Skeletal Muscle Cells, and Adipocytes. Pharm Biol 2008; 46:96–104.
96. Samarghandian S, Farkhondeh T, Samini F, Borji A. Protective Effects of Carvacrol against Oxidative Stress Induced by Chronic Stress in Rat’s Brain, Liver, and Kidney. Biochem Res Int 2016; 2016:2645237.
97. Zheng Y, Wang X, Ji S, Tian S, Wu H, Luo P, et al. Mepenzolate bromide promotes diabetic wound healing by modulating inflammation and oxidative stress. Am J Transl Res 2016; 8:2738–2747.
98. Dias JA, Fredrikson GN, Ericson U, Gullberg B, Hedblad B, Engström G, et al. Low-Grade Inflammation, Oxidative Stress and Risk of Invasive Post-Menopausal Breast Cancer - A Nested Case-Control Study from the Malmö Diet and Cancer Cohort. PLoS One 2016; 11:e0158959.
99. AI-Trad B, AI-Batayneh K, EI-Metwally S, Alhazimi A, Ginawi I, Alaraj M, et al. Albuminuria and Renal Extracellular Matrix. Eur Rev Med Pharmacol Sci 2016; 20:2680–2688.
100. Smith A, Howell D, Patmore R, Jack A, Roman E. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer 2011; 105:1684–1692.
101. Majdalawieh AF, Fayyad MW, Nasrallah GK. Anti-cancer properties and mechanisms of action of thymoquinone, the major active ingredient of Nigella sativa. Crit Rev Food Sci Nutr 2017; 57:3911–3928.
102. El-Mahdy MA, Zhu Q, Wang QE, Wani G, Wani AA. Thymoquinone induces apoptosis through activation of caspase-8 and mitochondrial events in p53-null myeloblastic leukemia HL-60 cells. Int J Cancer 2005; 117:409–417.
103. Alhosin M, Abusnina A, Achour M, Sharif T, Muller C, Peluso J, et al. Induction of apoptosis by thymoquinone in lymphoblastic leukemia Jurkat cells is mediated by a p73-dependent pathway which targets the epigenetic integrator UHRF1. Biochem Pharmacol 2010; 79:1251–1260.
104. Ashraf W, Ibrahim A, Alhosin M, Zaayter L, Ouararhni K, Papin C, et al. The epigenetic integrator UHRF1: on the road to become a universal biomarker for cancer. Oncotarget 2017; 8:51946–51962.
105. Abusnina A, Alhosin M, Keravis T, Muller CD, Fuhrmann G, Bronner C, et al. Down-regulation of cyclic nucleotide phosphodiesterase PDE1A is the key event of p73 and UHRF1 deregulation in thymoquinone-induced acute lymphoblastic leukemia cell apoptosis. Cell Signal 2011; 23:152–60.
106. Pang J, Shen N, Yan F, Zhao N, Dou L, Wu LC, et al. Thymoquinone exerts potent growth-suppressive activity on leukemia through DNA hypermethylation reversal in leukemia cells. Oncotarget 2017; 8:34453–34467.
107. Salim LZA, Mohan S, Othman R, Abdelwahab SI, Kamalidehghan B, Sheikh BY, et al. Thymoquinone induces mitochondria-mediated apoptosis in acute lymphoblastic leukaemia in vitro. Molecules 2013; 18:11219–40.
108. Ali Salim LZ, Othman R, Abdulla MA, Al-Jashamy K, Mohd AH, Hassandarvish P, et al. Thymoquinone Inhibits Murine Leukemia WEHI-3 Cells In Vivo and In Vitro. Wang Z, editor. PLoS One 2014; 9:e115340.
109. Dergarabetian EM, Ghattass KI, El-Sitt SB, Al-Mismar RM, El-Baba CO, Itani WS, et al. Thymoquinone induces apoptosis in malignant T-cells via generation of ROS. Front Biosci (Elite Ed) 2013; 5:706–19.
110. Soltani A, Pourgheysari B, Shirzad H, Sourani Z. Antiproliferative and Apoptosis-Inducing Activities of Thymoquinone in Lymphoblastic Leukemia Cell Line. Indian J Hematol Blood Transfus 2017; 33:516–524.
111. Diab-Assaf M, Semaan J, El-Sabban M, Al Jaouni SK, Azar R, Kamal MA, et al. Inhibition of Proliferation and Induction of Apoptosis by Thymoquinone via Modulation of TGF Family, p53, p21 and Bcl-2α in Leukemic Cells. Anticancer Agents Med Chem 2018; 18:210–215.
112. Hussain AR, Ahmed M, Ahmed S, Manogaran P, Platanias LC, Alvi SN, et al. Thymoquinone suppresses growth and induces apoptosis via generation of reactive oxygen species in primary effusion lymphoma. Free Radic Biol Med 2011; 50:978–87.
113. Hussain AR, Uddin S, Ahmed M, Al-Dayel F, Bavi PP, Al-Kuraya KS. Phosphorylated IκBα predicts poor prognosis in activated B-cell lymphoma and its inhibition with thymoquinone induces apoptosis via ROS release. Climent JAM, editor. PLoS One 2013; 8:e60540.
114. Zihlif MA, Mahmoud IS, Ghanim MT, Zreikat MS, Alrabadi N, Imraish A, et al. Thymoquinone efficiently inhibits the survival of EBV-infected B cells and alters EBV gene expression. Integr Cancer Ther 2013; 12:257–63.
115. Li F, Rajendran P, Sethi G. Thymoquinone inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway. Br J Pharmacol 2010; 161:541–54.
116. Badr G, Mohany M, Abu-Tarboush F. Thymoquinone decreases F-actin polymerization and the proliferation of human multiple myeloma cells by suppressing STAT3 phosphorylation and Bcl2/Bcl-XL expression. Lipids Health Dis 2011; 10:236.
117. Effenberger-Neidnicht K, Schobert R. Combinatorial effects of thymoquinone on the anti-cancer activity of doxorubicin. Cancer Chemother Pharmacol 2011; 67:867–74.
118. Banerjee S, Kaseb AO, Wang Z, Kong D, Mohammad M, Padhye S, et al. Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Cancer Res 2009; 69:5575–83.
119. Jafri SH, Glass J, Shi R, Zhang S, Prince M, Kleiner-Hancock H. Thymoquinone and cisplatin as a therapeutic combination in lung cancer: In vitro and in vivo. J Exp Clin Cancer Res 2010; 29:87.
120. Khalife R, El-Hayek S, Stephany E-H, Tarras O, Hodroj MH, Rizk S. Antiproliferative and proapoptotic effects of topotecan in combination with thymoquinone on acute myelogenous leukemia. Clin Lymphoma Myeloma Leuk 2014; 14 Suppl:S46-55.
121. Siveen KS, Mustafa N, Li F, Kannaiyan R, Ahn KS, Kumar AP, et al. Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-κB regulated gene products in multiple myeloma xenograft mouse model. Oncotarget 2014; 5:634–48.
122. Pazhouhi M, Sariri R, Rabzia A, Khazaei M. Thymoquinone synergistically potentiates temozolomide cytotoxicity through the inhibition of autophagy in U87MG cell line. Iran J Basic Med Sci 2016; 19:890–898.
123. al-Shabanah OA, Badary OA, Nagi MN, al-Gharably NM, al-Rikabi AC, al-Bekairi AM. Thymoquinone protects against doxorubicin-induced cardiotoxicity without compromising its antitumor activity. J Exp Clin Cancer Res 1998; 17:193–8.
124. Nagi MN, Mansour MA. Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection. Pharmacol Res 2000; 41:283–9.
125. Brown RK, Wilson G, Tucci MA, Benghuzzi HA. The effects of thymoquinone and Doxorubicin on leukemia and cardiomyocyte cell lines. Biomed Sci Instrum 2014; 50:391–6.
126. Matthaus B, Özcan MM. Fatty Acids, Tocopherol, and Sterol Contents of Some Nigella Species Seed Oil. Czech J Food Sci 2011; 29:145–150.
127. Hamrouni-Sellami I, Kchouk ME, Marzouk B. Lipid and aroma composition of black cumin (Nigella sativa L.) seeds from Tunisia. J Food Biochem 2008; 32:335–352.
128. Benkaci-Ali F, Baaliouamer A, Wathelet JP, Marlier M. Chemical Composition and physiochemical characteristics of fixed oils from Algerian Nigella sativa seeds. Chem Nat Compd 2012; 47:811–815.
129. Juhaimi F Al, Matthäus B, Ghafoora K, ElBabiker EF, Özcan MM. Fatty acids, tocopherols, minerals contents of Nigella sativa and Trigonella foenum-graecum seed and seed oils. Riv Ital delle Sostanze Grasse 2016; 93:165–171.
130. Al-Jasass FM, Al-Jasser MS. Chemical composition and fatty acid content of some spices and herbs under Saudi Arabia conditions. ScientificWorldJournal 2012; 2012:859892.
131. Cheikh-Rouhou S, Besbes S, Hentati B, Blecker C, Deroanne C, Attia H. Nigella sativa L.: Chemical composition and physicochemical characteristics of lipid fraction. Food Chem 2007; 101:673–681.
132. Toma CC, Simu GM, Hanganu D, Olah N, Vata FMG, Hammami C, et al. Chemical composition of the Tunisian Nigella sativa. Note I. Profile on essential oil. Farmacia 2010; 58:458–464.
133. Nickavar B, Mojab F, Javidnia K, Ali M, Amoli R. Chemical Composition of the Fixed and Volatile Oils of Nigella sativa L. from Iran. Z Naturforsch 2003; 58:629–631.
134. Gokyer A. Determination of Physicochemical Properties of Nigella sativa Seed Oil from Balıkesir Region , Turkey. Chem Process Eng Res 2016; 41:43–46.
135. Akloul R, Benkaci-Ali F, Zerrouki M, Eppe G. Composition and biological activities of the essential oil of Nigella sativa seeds isolated by accelerated microwave steam distillation with cryogenic grinding. Am J Essent Oils Nat Prod AJEONP 2014; 1:23–33.
136. Botnick I, Xue W, Bar E, Ibdah M, Schwartz A, Joel DM, et al. Distribution of primary and specialized metabolites in Nigella sativa seeds, a spice with vast traditional and historical uses. Molecules 2012; 17:10159–77.
137. Toma CC, Simu GM, Olah N, Georgiana FM. Chemical composition of the Tunisian Nigella sativa. Note I. Profile on essential oil. Farmacia 2010; 58:458–464.
138. Bourgou S, Ksouri R, Bellila A, Skandrani I, Falleh H, Marzouk B. Phenolic composition and biological activities of Tunisian Nigella sativa L. shoots and roots. C R Biol 2008; 331:48–55.
139. Houghton P, Zarka R, de las Heras B, Hoult J. Fixed Oil of Nigella sativa and Derived Thymoquinone Inhibit Eicosanoid Generation in Leukocytes and Membrane Lipid Peroxidation. Planta Med 1995; 61:33–36.
140. El-Dakhakhny M, Madi N., Lembert N, Ammon HP. Nigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygenase products in polymorphonuclear leukocytes from rats. J Ethnopharmacol 2002; 81:161–164.
141. Mansour M, Tornhamre S. Inhibition of 5-lipoxygenase and Leukotriene C4 Synthase in Human Blood Cells by Thymoquinone. J Enzyme Inhib Med Chem 2004; 19:431–436.
142. Mohamed A, Shoker A, Bendjelloul F, Mare A, Alzrigh M, Benghuzzi H, et al. Improvement of experimental allergic encephalomyelitis (EAE) by thymoquinone; an oxidative stress inhibitor. Biomed Sci Instrum 2003; 39:440–445.
143. Mohamed A, Waris HM, Ramadan H, Qureshi M, Kalra J. Amelioration of Chronic Relapsing Experimental autoimmune encephalomyelitis (CR-EAE) using thymoquinone. In: Biomedical Sciences Instrumentation. 2009; 274–279.
144. Mahgoub AA. Thymoquinone protects against experimental colitis in rats. Toxicol Lett 2003; 143:133–143.
145. Juhás S, Cikos S, Czikková S, Veselá J, Il’ková G, Hájek T, et al. Effects of borneol and thymoquinone on TNBS-induced colitis in mice. Folia Biol (Praha) 2008; 54:1–7.
146. Emekli-Alturfan E, Yarat A, Tunali-Akbay T, Isik F, Yenidogan G, Sener G, et al. Effect of black cumin (Nigella sativa) seed oil on gastric tissue in experimental colitis. Adv Environ Biol 2011; 5:483–490.
147. Isik F, Tunali Akbay T, Yarat A, Genc Z, Pisiriciler R, Caliskan-Ak E, et al. Protective Effects of Black Cumin (Nigella sativa) Oil on TNBS-Induced Experimental Colitis in Rats. Dig Dis Sci 2011; 56:721–730.
148. Suguna P, Geetha A, Aruna R, Siva GV. Effect of thymoquinone on ethanol and high fat diet induced chronic pancreatitis - a dose response study in rats. Indian J Exp Biol 2013; 51:292–302.
149. Mutabagani A, El-Mahdy SAM. A study of the anti-inflammatory activity of Nigella sativa L. and thymoquinone in rats. Saudi Pharm J 1997; 5:110–113.
150. Hajhashemi V, Ghannadi A, Jafarabadi H. Black cumin seed essential oil, as a potent analgesic and antiinflammatory drug. Phyther Res 2004; 18:195–199.
151. Al-Ghamdi MS. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol 2001; 76:45–48.