Cardiovascular benefits of black cumin (Nigella sativa)

Cardiovascular Toxicology

Volumn 13, Issue 1, 2013, Pages 9-21

  Shabana, Adel ^a,b   El Menyar, Ayman ^b,c   Asim, Mohammad ^c   Al Azzeh, Hiba ^d   Al Thani, Hassan ^a  

^a HAMAD MEDICAL CORPORATION   (Qatar)

^b WEILL CORNELL MEDICAL COLLEGE   (Qatar)

^c HAMAD GENERAL HOSPITAL   (Qatar)

^d Al Ghad Technology for Food Additives (MVM(Path))   (Jordan)

Author keywords

Black seeds; Cardiovascular; Cumin; Nigella sativa; Thymoquinone

Indexed keywords

CHOLESTEROL; CISPLATIN; CYCLOPHOSPHAMIDE; CYCLOSPORIN A; DOXORUBICIN; GEMCITABINE; GENTAMICIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IFOSFAMIDE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; METFORMIN; NIGELLA SATIVA EXTRACT; OXALIPLATIN; SIMVASTATIN; THYMOQUINONE; TRIACYLGLYCEROL;

ACUTE TOXICITY; ANTHELMINTIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTIMICROBIAL ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; ARTICLE; ASTHMA; AUTOIMMUNE DISEASE; BLOOD PRESSURE; CARDIOMYOPATHY; CARDIOTOXICITY; CARDIOVASCULAR DISEASE; CHEMICAL COMPOSITION; CHRONIC TOXICITY; CONTACT DERMATITIS; DIABETES MELLITUS; DRUG CYTOTOXICITY; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; ENDOTHELIAL DYSFUNCTION; HEART MUSCLE CONTRACTILITY; HEART PROTECTION; HEART RATE; HUMAN; HYPERCHOLESTEROLEMIA; HYPERHOMOCYSTEINEMIA; HYPERTENSION; IMMUNOMODULATION; INSULIN DEPENDENT DIABETES MELLITUS; KIDNEY DISEASE; LIVER INJURY; LIVER PROTECTION; METABOLIC SYNDROME X; NEPHROTOXICITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PLANT SEED; PRIORITY JOURNAL; REPERFUSION INJURY; RHEUMATOID ARTHRITIS;

ANIMALS; CARDIOVASCULAR AGENTS; CARDIOVASCULAR DISEASES; CLINICAL TRIALS AS TOPIC; HUMANS; NIGELLA SATIVA; PLANT EXTRACTS;

CUMINUM CYMINUM; NIGELLA SATIVA; RANUNCULACEAE;

EID: 84872595308     PISSN: 15307905     EISSN: 15590259     Source Type: Journal    
DOI: 10.1007/s12012-012-9181-z     Document Type: Article

References (117)

1. Cooper, E. L. (2004). Complementary and alternative medicine, when rigorous, can be science. Evidence-Based Complementary and Alternative Medicine, 1, 1-4.
2. Zohary, D.; & Hopf, M. (2001). Domestication of plants in the old world. Oxford: Oxford University Press.
3. Ghosheh, A. O.; Houdi, A. A.; & Crooks, A. P. (1998). High performance liquid chromatographic analysis of the pharmacologically active quinines and related compounds in the oil of the black seed [N. sativa L.]. Journal of Pharmaceutical and Biomedical Analysis, 19, 757-762. (Pubitemid 29092778)
4. Padhye, S.; Banerjee, S.; Ahmad, A.; et al. (2008). From here to eternity - The secret of Pharaohs: Therapeutic potential of black cumin seeds and beyond. Cancer Therapy, 6(b), 495-510.
5. Al-Bukhari, M. I. (1976). Division [71] on medicine. In Sahih. Al-Bukhari (Ed.), The collection of authentic sayings of Prophet Mohammad [peace be upon him] (2nd ed.). Ankara, Turkey: Hilal Yayinlari.
6. Bakathir, H.; & Abbas, N. (2011). Detection of the antibacterial effect of Nigella sativa ground seeds with water. African Journal of Traditional, Complementary and Alternative Medicines, 8(2), 159-164.
7. Mannan, A.; & Kahvic, M. (2010). Ibn Sina: A tribute. The Gulf Journal of Oncology, 7, 60-63.
8. Aggarwal, B. B.; Kunnumakkara, A. B.; Harikumar, K. B.; et al. (2008). Potential of spice-derived phytochemicals for cancer prevention. Planta Medica, 74(13), 1560-1569.
9. Randhawa, M.; & Alghamdi, M. (2011). Anticancer activity of Nigella sativa [black seed] - A review. American Journal of Chinese Medicine, 39(6), 1075-1091.
10. Aqel, M.; & Shaheen, R. (1996). Effects of the volatile oil of Nigella sativa seeds on the uterine smooth muscle of rat and guinea pig. Journal of Ethnopharmacology, 52, 23-26. (Pubitemid 26134508)
11. Chakravorty, N. (1993). Inhibition of histamine release from mast cells by Nigellone. Annals of Allergy, 70, 237-242.
12. Zaoui, A.; Cherrah, Y.; Lacaille-Dubois, M. A.; et al. (2000). Diuretic and hypotensive effects of Nigella sativa in the spontaneously hypertensive rat. Therapie, 55, 379-382. (Pubitemid 30481173)
13. Al-Hader, A.; Aqel, A.; & Hassan, Z. (1993). Hypoglycemic effects of the volatile oil of Nigella sativa seeds. International Journal of Pharmacology, 31, 96-100. (Pubitemid 23177256)
14. Khan, M. A.; Ashfaq, M. K.; Zuberi, H. S.; et al. (2003). The in vivo antifungal activity of the aqueous extract from Nigella sativa seeds. Phytotherapy Research, 17, 183-186. (Pubitemid 36262271)
15. Al-Ghamdi, M. S. (2001). The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. Journal of Ethnopharmacology, 76, 45-48. (Pubitemid 32510729)
16. Worthen, D. R.; Ghosheh, O. A.; & Crooks, P. A. (1998). The in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa L. Anticancer Research, 18, 1527-1532. (Pubitemid 28342555)
17. Ali, B.; & Blunden, G. (2003). Pharmacological and toxicological properties of Nigella sativa. Phytotherapy Research, 17(4), 299-305. (Pubitemid 36565330)
18. Nickavar, B.; Mojab, F.; Javidnia, K.; & Amoli, M. (2003). Chemical composition of the fixed and volatile oils of Nigella sativa L. from Iran. Zeitschrift für Naturforschung C, 58(9-10), 629-631. (Pubitemid 37224250)
19. Houghton, P.; Zarka, R.; de las Heras, B.; & Hoult, J. R. (1995). Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Medica, 61(1), 33-36.
20. Abou-Basha, L.; Rashed, M. S.; & Aboul-Enein, H. Y. (1995). Thin layer chromatographic assay of thymoquinone in black seed oil and identification of dithymoquinone and thymol. Journal of Liquid Chromatography, 18, 105-115.
21. Al-Ali, A.; Alkhawajah, A. A.; Randhawa, M. A.; & Shaikh, N. A. (2008). Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats. Journal of Ayub Medical College, Abbottabad, 20(2), 25-27.
22. Kaleem, M.; Kirmani, D.; Asif, M.; et al. (2006). Biochemical effects of Nigella sativa L. seeds in diabetic rats. Indian Journal of Experimental Biology, 44(9), 745-748. (Pubitemid 44369305)
23. Bamosa, A.; Kaatabi, H.; Lebdaa, F.; et al. (2010). Effect of Nigella sativa seeds on the glycemic control of patients with type 2 diabetes mellitus. Indian Journal of Physiology and Pharmacology, 54(4), 344-354.
24. Benhaddou-Andaloussi, A.; Martineau, L.; Vuong, T.; et al. (2011). The in vivo antidiabetic activity of Nigella sativa is mediated through activation of the AMPK pathway and increased muscle Glut4 content. Evidence-Based Complementary and Alternative Medicine. Article ID: 538671. [Epub 2011 April 14].
25. Kanter, M.; Akpolat, M.; & Aktas, C. (2009). Protective effects of the volatile oil of Nigella sativa seeds on beta-cell damage in streptozotocin-induced diabetic rats: A light and electron microscopic study. Journal of Molecular Histology, 40(5-6), 379-385.
26. Demir, H.; Kanter, M.; Coskun, O.; et al. (2006). Effect of black cumin [Nigella sativa] on heart rate, some hematological values, and pancreatic beta-cell damage in cadmium-treated rats. Biological Trace Element Research, 110(2), 151-162. (Pubitemid 43997961)
27. Abdelmeguid, N.; Fakhoury, R.; Kamal, S.; & Al Wafai, R. (2010). Effects of Nigella sativa and thymoquinone on biochemical and subcellular changes in pancreatic β-cells of streptozotocin-induced diabetic rats. Journal of Diabetes, 2(4), 256-266.
28. Kanter, M.; Meral, I.; Yener, Z.; et al. (2003). Partial regeneration/proliferation of the beta-cells in the islets of Langerhans by Nigella sativa L. in streptozotocin-induced diabetic rats. Tohoku Journal of Experimental Medicine, 201(4), 213-219. (Pubitemid 38128805)
29. El-Dakhakhny, M.; Mady, N.; Lembert, N.; & Ammon, H. (2002). The hypoglycemic effect of Nigella sativa oil is mediated by extrapancreatic actions. Planta Medica, 68(5), 465-466. (Pubitemid 34606696)
30. Fararh, K.; Atoji, Y.; Shimizu, Y.; et al. (2004). Mechanisms of the hypoglycaemic and immunopotentiating effects of Nigella sativa L. oil in streptozotocin-induced diabetic hamsters. Research in Veterinary Science, 77(2), 123-129. (Pubitemid 38950326)
31. Kanter, M. (2008). Effects of Nigella sativa and its major constituent, thymoquinone on sciatic nerves in experimental diabetic neuropathy. Neurochemical Research, 33(1), 87-96. (Pubitemid 350242795)
32. Hamdy, N.; & Taha, R. (2009). Effects of Nigella sativa oil and thymoquinone on oxidative stress and neuropathy in streptozotocin-induced diabetic rats. Pharmacology, 84(3), 127-134.
33. Meddah, B.; Ducroc, R.; El Abbes Faouzi, M.; et al. (2009). Nigella sativa inhibits intestinal glucose absorption and improves glucose tolerance in rats. Journal of Ethnopharmacology, 121(3), 419-424.
34. Rchid, H.; Chevassus, H.; Nmila, R.; et al. (2004). Nigella sativa seed extracts enhance glucose-induced insulin release from rat-isolated Langerhans islets. Fundamental & Clinical Pharmacology, 18(5), 525-529. (Pubitemid 39468960)
35. Le, P.; Benhaddou-Andaloussi, A.; Elimadi, A.; et al. (2004). The petroleum ether extract of Nigella sativa exerts lipid-lowering and insulin-sensitizing actions in the rat. Journal of Ethnopharmacology, 94(2-3), 251-259. (Pubitemid 39119926)
36. Benhaddou-Andaloussi, A.; Martineau, L.; Vallerand, D.; et al. (2010). Multiple molecular targets underlie the antidiabetic effect of Nigella sativa seed extract in skeletal muscle, adipocyte and liver cells. Diabetes, Obesity & Metabolism, 12(2), 148-157.
37. Najmi, A.; Nasiruddin, M.; Khan, R. A.; & Haque, S. F. (2008). Effect of Nigella sativa oil on various clinical and biochemical parameters of insulin resistance syndrome. International Journal of Diabetes in Developing Countries, 28(1), 11-14.
38. Qidwai, W.; Hamza, H.; & Gilani, A. (2009). Effectiveness, safety and tolerability of powdered Nigella sativa [kalonji] seed in capsules on serum lipid levels, blood sugar, blood pressure and body weight in adults: Results of a randomized, double blind controlled trial. Journal of Alternative and Complementary Medicine, 15, 639-644.
39. Nader, M.; El-Agamy, D.; & Suddek, G. (2010). Protective effects of propolis and thymoquinone on development of atherosclerosis in cholesterol-fed rabbits. Archives of Pharmacal Research, 33(4), 637-643.
40. Al-Naqeep, G.; Al-Zubairi, A. S.; Ismail, M.; et al. (2011). Antiatherogenic potential of Nigella sativa seeds and oil in diet-induced hypercholesterolemia in rabbits. Evidence-Based Complementary and Alternative Medicine. doi: 10.1093/ecam/neq071.
41. El-Dakhakhny, M.; Mady, N.; & Halim, M. (2000). Nigella sativa L. oil protects against induced hepatotoxicity and improves serum lipid profile in rats. Arzneimittel-Forschung, 50(9), 832-836.
42. Zaoui, Y.; Cherrah, K.; Alaoui, K.; et al. (2002). Effects of Nigella sativa fixed oil on blood homeostasis in rat. Journal of Ethnopharmacology, 79(1), 23-26. (Pubitemid 34017236)
43. Bhatti, I. U.; Ur Rehman, F.; Khan, M. A.; & Marwat, S. K. (2009). Effect of prophetic medicine kalonji [Nigella sativa l.] on lipid profile of human beings. An invivo approach. World Applied Sciences Journal, 6(8), 1053-1057.
44. Bamosa, A. O.; Ali, B. A.; & Sowayan, S. A. (1997). Effect of oral ingestion of Nigella sativa seeds on some blood parameters. Saudi Pharmaceutical Journal, 5, 126-129. (Pubitemid 27438159)
45. Tasawar, Z.; Siraj, Z.; Ahmad, N.; & Lashari, M. H. (2011). The effects of Nigella sativa [Kalonji] on lipid profile in patients with stable coronary artery disease in Multan, Pakistan. Pakistan Journal of Nutrition, 10(2), 162-167.
46. Dehkordi, F.; & Kamkhah, A. (2008). Antihypertensive effect of Nigella sativa seed extract in patients with mild hypertension. Fundamental & Clinical Pharmacology, 22(4), 447-452.
47. Bamosa, A. O.; Ali, B. A.; & Al-Hawsawi, Z. A. (2002). The effect of thymoquinone on blood lipids in rats. Indian Journal of Physiology and Pharmacology, 46, 195-201. (Pubitemid 34415118)
48. Kanter, M.; Coskun, O.; & Budancamanak, M. (2005). 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 Journal of Gastroenterology, 11(42), 6684-6688. (Pubitemid 43072712)
49. Mat, M. C.; Mohamed, A. S.; & Hamid, S. S. (2011). Primary human monocyte differentiation regulated by Nigella sativa pressed oil. Lipids in Health and Disease, 10, 216-226.
50. Krieger, M. (1997). The other site of scavenger receptors. Pattern recognition and host defense. Current Opinion in Lipidology, 8, 275-280. (Pubitemid 27462434)
51. Vanhoutte, P.; Shimokawa, H.; Tang, E. H.; & Feletou, M. (2009). Endothelial dysfunction and vascular disease. Acta Physiology [Oxford], 196(2), 193-222.
52. Idris-Khodja, N.; & Schini-Kerth, V. (2012). Thymoquinone improves aging-related endothelial dysfunction in the rat mesenteric artery. Naunyn Schmiedebergs Arch Pharmacology [Epub ahead of print].
53. Enomoto, S.; Asano, R.; Iwahori, Y.; et al. (2001). Hematological studies on black cumin oil from the seeds of Nigella sativa L. Biological and Pharmaceutical Bulletin, 24(3), 307-310. (Pubitemid 32237174)
54. Mahfouz, M.; & El-Dakhakhny, M. (1960). Chemical and pharmacological properties of the new antiasthmatic drug, nigellone. Egyptian Pharmacology Bulletin, 42, 411-424.
55. El-Tahir, K.; Ashour, M.; & Al-Harbi, M. (1993). The cardiovascular actions of the volatile oil of the black seed [Nigella sativa] in rats: Elucidation of the mechanism of action. General Pharmacology, 24, 1123-1131. (Pubitemid 23283080)
56. Khattab, M. M.; & Nagi, M. N. (2007). Thymoquinone supplementation attenuates hypertension and renal damage in nitric oxide deficient hypertensive rats. Phytotherapy Research, 21, 410-414. (Pubitemid 46715078)
57. El-Bahai, M. N.; Al-Hariri, M. T.; Yar, T.; & Bamosa, A. O. (2009). Cardiac inotropic and hypertrophic effects of Nigella sativa supplementation in rats. International Journal of Cardiology, 131(3), e115-e117.
58. Al-Hariri, M. T.; Yar, T.; Bamosa, A. O.; & El-Bahai, M. N. (2009). Effects of two-month Nigella sativa supplementation on cardiac hemodynamics and adrenergic responsiveness. The Journal of Pakistan Medical Association, 59(6), 363-368.
59. Boskabady, M. H.; Shafie, M. N.; & Parsaee, H. (2005). Effect of aqueous and macerated extracts from Nigella sativa on guinea pig isolated heart activity. Pharmazie, 60(12), 943-948. (Pubitemid 41820763)
60. Shafie, M. N.; Boskabady, M. H.; & Parsaee, H. (2005). Effect of aqueous extract from Nigella sativa L. on guinea pig isolated heart. Indian Journal of Experimental Biology, 43(7), 635-639. (Pubitemid 40962674)
61. Rezzani, R. (2006). Exploring cyclosporine A-side effects and the protective role-played by antioxidants: The morphological and immunohistochemical studies. Histology and Histopathology, 21, 301-316. (Pubitemid 43033739)
62. Nishiyama, A.; Kobori, H.; Fukui, T.; et al. (2003). Role of angiotensin II and reactive oxygen species in cyclosporine A-dependent hypertension. Hypertension, 42, 754-760. (Pubitemid 37237321)
63. Ebru, U.; Burak, U.; Yusuf, S.; et al. (2008). Cardioprotective effects of Nigella sativa oil on cyclosporine A-induced cardiotoxicity in rats. Basic & Clinical Pharmacology & Toxicology, 103, 574-580.
64. Nagi, M. N.; Al-Shabanah, O.; Hafez, M.; & Sayed-Ahmed, M. (2011). Thymoquinone supplementation attenuates cyclophosphamide-induced cardiotoxicity in rats. Journal of Biochemical and Molecular Toxicology, 25(3), 135-142.
65. Al-Shabanah, O. A.; Badary, O. A.; Nagi, M. N.; et al. (1998). Thymoquinone protects against doxorubicin-induced cardiotoxicity without compromising its antitumor activity. Journal of Experimental & Clinical Cancer Research, 17, 193-198. (Pubitemid 28335578)
66. Effenberger-Neidnicht, K.; & Schobert, R. (2011). Combinatorial effects of thymoquinone on the anti-cancer activity of doxorubicin. Cancer Chemotherapy and Pharmacology, 67(4), 867-874.
67. Nagi, M. N.; & Mansour, M. (2000). Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: A possible mechanism of protection. Pharmacological Research, 41(3), 283-289. (Pubitemid 30663132)
68. El-Saleh, S. C.; Al-Sagair, O. A.; & Al-Khalaf, M. I. (2004). Thymoquinone and Nigella sativa oil protection against methionine-induced hyperhomocysteinemia in rats. International Journal of Cardiology, 93(1), 19-23. (Pubitemid 38068504)
69. Ali, B.; Bamosa, A.; & Al-Hawsawi, Z. (2003). Effect of Nigella sativa on blood lipids in normal rats. Arab Gulf Journal of Scientific Research, 21, 102-109. (Pubitemid 36946841)
70. Dahri, A. H.; Chandiol, A. M.; Rahoo, A. A.; & Memon, R. A. (2005). Effect of Nigella sativa [kalonji] on serum cholesterol of albino rats. Journal of Ayub Medical College, Abbottabad, 17(2), 72-74.
71. Yar, T.; El-Hariri, M.; El-Bahai, M.; et al. (2008). Effects of Nigella sativa supplementation for one month on cardiac reserve in rats. Indian Journal of Physiology and Pharmacology, 52(2), 141-148.
72. Ragheb, A.; Elbarbry, F.; Prasad, K.; et al. (2008). Attenuation of the development of hypercholesterolemic atherosclerosis by thymoquinone. International Journal of Angiology, 17(4), 186-192.
73. Sultan, M.; Butt, M.; Ahmad, R.; et al. (2012). Supplementation of Nigella sativa fixed and essential oil mediates potassium bromate induced oxidative stress and multiple organ toxicity. Pakistan Journal of Pharmaceutical Sciences, 25(1), 175-181.
74. Woo, C.; Kumar, A.; Sethi, G.; & Tan, K. (2012). Thymoquinone: Potential cure for inflammatory disorders and cancer. Biochemical Pharmacology, 83(4), 443-451.
75. Tripathi, Y.; Chaturvedi, A.; & Pandey, N. (2012). Effect of Nigella sativa seeds extracts on iNOS through antioxidant potential only: Crude/total extract as molecular therapy drug. Indian Journal of Experimental Biology, 50(6), 413-418.
76. Badary, O. A.; Abdel Naim, A. B.; Abdel Wahab, M. H.; & Hamada, F. M. (2000). Induced hyperlipedimic nephropathy in rats. Toxicology, 143(3), 219-226. (Pubitemid 30089521)
77. Sayed-Ahmed, M. M.; & Nagi, M. N. (2007). Thymoquinone supplementation prevents the development of gentamicin-induced acute renal toxicity in rats. Clinical and Experimental Pharmacology and Physiology, 34, 399-405. (Pubitemid 46494460)
78. Kanter, M.; Demir, H.; Karakaya, C.; & Ozbek, H. (2005). Gastroprotective activity of Nigella sativa L. oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats. World Journal of Gastroenterology, 11, 6662-6666. (Pubitemid 43072707)
79. Rastogi, L.; Feroz, S.; Pandey, B. N.; et al. (2010). Protection against radiation-induced oxidative damage by an ethanolic extract of Nigella sativa L. International Journal of Radiation Biology, 86(9), 719-731.
80. Yildiz, F.; Coban, S.; Terzi, A.; et al. (2008). Nigella sativa relieves the deleterious effects of ischemia reperfusion injury on liver. World Journal of Gastroenterology, 14(33), 5204-5209.
81. Coban, S.; Yildiz, F.; Terzi, A.; et al. (2010). The effects of Nigella sativa on bile duct ligation induced-liver injury in rats. Cell Biochemistry and Function, 28(1), 83-88.
82. Daba, M. H.; & Abdel-Rahman, M. S. (1998). Hepatoprotective activity of thymoquinone in isolated rat hepatocytes. Toxicology Letters, 95(1), 23-29.
83. Nagi, M. N.; Alam, K.; Badary, O. A.; et al. (1999). Thymoquinone protects against carbon tetrachloride hepatotoxicity in mice via an antioxidant mechanism. Biochemistry and Molecular Biology International, 47(1), 153-159. (Pubitemid 29112715)
84. Nili-Ahmadabadi, A.; Tavakoli, F.; Hasanzadeh, G.; et al. (2011). Protective effect of pretreatment with thymoquinone against Aflatoxin B[1] induced liver toxicity in mice. Daru, 19(4), 282-287.
85. Farrag, A.; Mahdy, K.; Abdel Rahman, G.; & Osfor, M. (2007). Protective effect of Nigella sativa seeds against lead-induced hepatorenal damage in male rats. Pakistan Journal of Biological Sciences, 10(17), 2809-2816. (Pubitemid 47597067)
86. Michel, C.; El-Sayed, N.; Moustafa, S.; et al. (2011). Phytochemical and biological investigation of the extracts of Nigella sativa L. seed waste. Drug Testing And Analysis, 3(4), 245-254.
87. Helal, G. (2010). Thymoquinone supplementation ameliorates acute endotoxemia-induced liver dysfunction in rats. Pakistan Journal of Pharmaceutical Sciences, 23(2), 131-137.
88. Salem, M. L. (2005). Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. International Immunopharmacology, 5, 1749-1770. (Pubitemid 41594584)
89. Boskabady, M. H.; Javan, H.; Sajady, M.; & Rakhshandeh, H. (2007). The possible prophylactic effect of N. sativa seed extract in asthmatic patients. Fundamental & Clinical Pharmacology, 21(5), 559-566. (Pubitemid 47404328)
90. Vaillancourt, F.; Silva, P.; Shi, Q.; et al. (2011). Elucidation of molecular mechanisms underlying the protective effects of thymoquinone against rheumatoid arthritis. Journal of Cellular Biochemistry, 112(1), 107-117.
91. Gheita, T.; & Kenawy, S. (2011). Effectiveness of Nigella sativa oil in the management of rheumatoid arthritis patients: A Placebo controlled study. Phytotherapy Research. doi: 10.1002/ptr.36 [Epub ahead of print].
92. Roepke, M.; Diestel, A.; Bajbouj, K.; et al. (2007). Lack of p53 augments thymoquinone-induced apoptosis and caspase activation in human osteosarcoma cells. Cancer Biology & Therapy, 6(2), 160-169. (Pubitemid 46641618)
93. Gali-Muhtasib, H.; Roessner, A.; & Schneider-Stock, R. (2006). Thymoquinone: A promising anti-cancer drug from natural sources. International Journal of Biochemistry & Cell Biology, 38(8), 1249-1253.
94. Sethi, G.; Ahn, K.; & Aggarwal, B. (2008). Targeting nuclear factor-{kappa}B activation pathway by thymoquinone: Role in suppression of antiapoptotic gene products and enhancement of apoptosis. Molecular Cancer Research, 6, 1059-1070.
95. Yi, T.; Cho, S.; Yi, Z.; et al. (2008). Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways. Molecular Cancer Therapeutics, 7(7), 1789-1796.
96. Kaseb, A. O.; Chinnakannu, K.; Chen, D.; et al. (2007). Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Cancer Research, 67, 7782-7788. (Pubitemid 47281372)
97. Abusnina, A.; Alhosin, M.; Keravis, T.; et al. (2011). Down-regulation of cyclic nucleotide phosphodiesterase PDE1A is the key event of p73 and UHRF1 deregulation in thymoquinone-induced acute lymphoblastic leukemia cell apoptosis. Cellular Signalling, 23(1), 152-160.
98. Hadjzadeh, M. A.; Keshavarzi, Z.; Tabatabaee-Yazdi, S.; et al. (2012). Effect of alcoholic extract of Nigella sativa on cisplatin-induced toxicity in rat. Iranian Journal of Kidney Diseases, 6(2), 99-104.
99. Badary, O. A.; Nagi, M. N.; Al-Shabanah, O. A.; et al. (1997). Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and potentiates its antitumor activity. Canadian Journal of Physiology and Pharmacology, 75(12), 1356-1361. (Pubitemid 28130377)
100. Badary, O. A. (1999). Thymoquinone attenuates ifosfamide-induced Fanconi syndrome in rats and enhances its antitumor activity in mice. Journal of Ethnopharmacology, 67(2), 135-142. (Pubitemid 29421667)
101. Banerjee, S.; Kaseb, A.; Wang, Z.; et al. (2009). Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Cancer Research, 69(13), 5575-5583.
102. Morsi, N. (2000). Antimicrobial effect of crude extracts of Nigella sativa on multiple antibiotics-resistant bacteria. Acta Microbiologica Polonica, 49(1), 63-74. (Pubitemid 30428450)
103. Hanafy, M. S.; & Hatem, M. E. (1991). Studies on the antimicrobial activity of Nigella sativa seed [black cumin]. Journal of Ethnopharmacology, 34(2-3), 275-278.
104. Kokoska, L.; Havlik, J.; Valterova, I.; et al. (2008). Comparison of chemical composition and antibacterial activity of Nigella sativa seed essential oils obtained by different extraction methods. Journal of Food Protection, 71(12), 2475-2480.
105. Hannan, A.; Saleem, S.; Chaudhary, S.; et al. (2008). Anti bacterial activity of Nigella sativa against clinical isolates of methicillin resistant Staphylococcus aureus. Journal of Ayub Medical College, Abbottabad, 20(3), 72-74.
106. Chaieb, K.; Kouidhi, B.; Jrah, H.; et al. (2011). Antibacterial activity of thymoquinone, an active principle of Nigella sativa and its potency to prevent bacterial biofilm formation. BMC Complementary and Alternative Medicine, 11, 29-34.
107. Khan, M. A.; Ashfaq, M. K.; Zuberi, H. S.; et al. (2003). The in vivo antifungal activity of the aqueous extract from Nigella sativa seeds. Phytotherapy Research, 17(2), 183-186. (Pubitemid 36262271)
108. Islam, S. K.; Ahsan, M.; Hassan, C. M.; & Malek, M. A. (1989). Antifungal activities of the oils of Nigella sativa seeds. Pakistan Journal of Pharmaceutical Sciences, 2(1), 25-28.
109. Ayaz, E.; Yilmaz, H.; Ozbek, H.; et al. (2007). The effect of Nigella sativa oil against Aspiculuris tetraptera and Hymenolepis nana in naturally infected mice. Saudi Medical Journal, 28(11), 1654-1657. (Pubitemid 350237976)
110. Aboul-Ela, E. I. (2002). Cytogenetic studies on Nigella sativa seeds extract and thymoquinone on mouse cells infected with schistosomiasis using karyotyping. Mutation Research, 516, 11-17. (Pubitemid 34415495)
111. Ilhan, A.; Gurel, A.; Armutcu, F.; et al. (2005). Antiepileptogenic and antioxidant effects of Nigella sativa oil against pentylenetetrazol-induced kindling in mice. Neuropharmacology, 49(4), 456-464. (Pubitemid 41169970)
112. Perveen, T.; Haider, S.; Kanwal, S.; & Haleem, D. J. (2009). Repeated administration of Nigella sativa decreases 5-HT turnover and produces anxiolytic effects in rats. Pakistan Journal of Pharmaceutical Sciences, 22(2), 139-144.
113. Hadjzadeh, M. A.; Khoei, A.; Hadjzadeh, Z.; & Parizady, M. (2007). Ethanolic extract of Nigella sativa L. seeds on ethylene glycol-induced kidney calculi in rats. Urology Journal, 4(2), 86-90.
114. Aqel, M. B. (1993). Effect of Nigella sativa seeds on intestinal smooth muscles. International Journal of Pharmacognosy, 31, 55-60. (Pubitemid 23142822)
115. Zaoui, A.; Cherrah, Y.; Mahassini, N.; et al. (2002). Acute and chronic toxicity of Nigella sativa fixed oil. Phytomedicine, 9(1), 69-74. (Pubitemid 34184213)
116. Badary, O. A.; Al-Shabanah, O. A.; Nagi, M. N.; et al. (1998). Acute and subchronic toxicity of thymoquinone in mice. Drug Development Research, 44, 56-61. (Pubitemid 28452876)
117. Vahdati-Mashhadian, N.; Rakhshandeh, H.; & Omidi, A. (2005). An investigation on LD50 and subacute hepatic toxicity of Nigella sativa seed extracts in mice. Pharmazie, 60(7), 544-547. (Pubitemid 41025573)