Cardio-protective and anti-cancer therapeutic potential of Nigella sativa

Document Type: Review Article


1 Department of Food Technology, PMAS Arid Agriculture University Rawalpindi, 43600 Pakistan

2 Department of Food Technology, PMAS Arid Agriculture University Rawalpindi, 43600 Pakistan Corn, Soybean and Wheat Quality Labs., 205 Williams Hall, 1680 Madison Avenue, Wooster, OH 44691 USA


Nigella sativa is the miraculous plant having a lot of nutritional and medicinal benefits, and attracts large number of nutrition and pharmacological researchers. N. sativa seed composition shows that it is the blessing of nature and it contains and many bioactive compounds like thymoquinone, α-hederin, alkaloids, flavonoids, antioxidants, fatty acids many other compounds that have positive effects on curing of different diseases. Several medicinal properties of N. sativa like its anti-cancer, anti-inflammatory, anti-diabetic, antioxidant activities and many others are well acknowledged. However, this article focuses on activity of N. sativa against cardiovascular diseases and cancer. For gathering required data the authors went through vast number of articles using search engines like Science direct, ELSEVIER, Pub Med, Willey on Line Library and Google scholar and the findings were classified on the basis of relevance of the topic and were reviewed in the article. N. sativa is rich source of different biologically active compounds and is found effective in controlling number of cardiovascular diseases and various cancers both in vivo and in vitro studies.


1. Paarakh PM. Nigella sativa Linn.–A comprehensive review. Indian J Natu Prod Res 2010; 1:409-429.

2. Grover J, Yadav S. Pharmacological actions and potential uses of Momordica charantia: a review. J Ethnopharmacol 2004; 93:123-132.

3. Mills S, Bone K. Principles and practice of phytotherapy. Modern herbal medicine: Churchill Livingstone; 2000.

4. 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 Pacific J Trop Biomed 2013; 3:337-352.

5. Al-Khalaf MI, Ramadan KS. Antimicrobial and Anti-cancer Activity of Nigella sativa oil-A Review. Aus J Basic Appl Sci 2013;7:505-514.

6. Ismail MYM. Therapeutic Role of Prophetic Medicine Habbat El Baraka (Nigella sativa L.)-A Review. World Appl Sci J 2009;7:1203-1208.

7. Gilani A, Jabeen Q, Khan M. A review of medicinal uses and pharmacological activities of Nigella sativa. Pak J Biol Sci 2004;7:441-451.

8. Zohary D, Hopf M, Weiss E. Domestication of Plants in the Old World: The origin and spread of domesticated plants in Southwest Asia, Europe, and the Mediterranean Basin: Oxford University Press; 2012.

9. Sharma NK, Ahirwar D, Jhade D, Gupta S. Medicinal and phamacological potential of Nigella sativa: A review. Ethnobot Rev 2009; 13:946-955.

10. Randhawa MA, Alghamdi MS. Anti-cancer activity of Nigella sativa (black seed)—A review. Am J Chin Med 2011; 39:1075-1091.

11. Nasir A, Siddiqui MY, Mohsin M. Therapeutic Uses of Shoneez (Nigella sativa Linn.) Mentioned in Unani System of Medicine-A Review. Int J Pharm Phytopharmaco Res 2014; 4: 47-49.

12. Al-Bukhari MI, Sahih Al-Bukhari. The Collection of Authentic Sayings of Prophet Mohammad (peace be upon him), Division 71 on Medicine. 2nd ed. Ankara, Turkey: Hilal Yayinlari; 1976.

13. Alwan A. Global status report on noncommunicable diseases 2010: World Health Organization; 2011.

14. WHO. Cardiovascular diseases 2013  [25/4/2014]. Available from:

15. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3:e442.

16. WHO. Cancer fact sheet 2013 [25/4/2014]. Available from: mediacentre/-factsheets/ fs297/en/.

17. Reuters T. Cancer cases worldwide likely to rise to 22 million new cases in 2 decades 2014 [29/4/2014]. Available from: cancer-cases-worldwide-likely-to-rise-to-22-million-new-cases-in-2-decades-1.2521156.

18. Warrier P, Nambiar V, Ramankutty C. Indian medicinal plants: a compendium of 500 species: Orient Longman Ltd. Chennai. 1996; 3:38-90.

19. Yarnell E, Abascal K. Nigella sativa: holy herb of the middle East. Altern Complement Ther 2011; 17:99-105.

20. Ramadan MF. Nutritional value, functional properties and nutraceutical applications of black cumin (Nigella sativa L.): an overview. Int J Food Sci Technol 2007; 42:1208-1218.

21. Goreja WC. Black seed: nature's miracle remedy: TNC International Inc; 2003.

22. Padhye S, Banerjee S, Ahmad A, Mohammad R, Sarkar FH. From here to eternity-the secret of Pharaohs: Therapeutic potential of black cumin seeds and beyond. Canc ther 2008; 6:495-510.

23. Sharma P, Yelne M, Dennis T, Joshi A, Billore K. Database on medicinal plants used in Ayurveda. The University of Virginia; 2000. accessed from:

24. Chakravarty N. Inhibition of histamine release from mast cells by nigellone. Ann Allergy 1993; 70:237-242.

25. Ali B, Blunden G. Pharmacological and toxicological properties of Nigella sativa. Phytother Res 2003; 17:299-305.

26. Khan M, Ashfaq M, Zuberi H, Mahmood M, Gilani A. The in vivo antifungal activity of the aqueous extract from Nigella sativa seeds. Phytother Res 2003; 17:183-186.

27. Al-Ghamdi M. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol 2001; 76:45-48.

28. Khan MA, Chen HC, Tania M, Zhang DZ. Anti-cancer activities of Nigella sativa (black cumin). Afr J Tradit Complement Altern Med 2011; 8:226-232.

29. Nergiz C, Ötleş S. Chemical composition of Nigella sativa L. seeds. Food Chem 1993; 48:259-261.

30. Khan MA. Chemical composition and medicinal properties of Nigella sativa Linn. Inflammopharmacol 1999; 7:15-35.

31. Nickavar B, Mojab F, Javidnia K, Amoli MR. Chemical composition of the fixed and volatile oils of Nigella sativa L. from Iran. Zeitschrift Fur Naturforschung C 2003; 58:629-631.

32. 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.

33. Yusuf S, Reddy S, Ôunpuu S, Anand S. Global burden of cardiovascular diseases part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation 2001; 104:2746-2753.

34. Mendis S, Puska P, Norrving B. Global atlas on cardiovascular disease prevention and control: World Health Organization; 2011.

35. 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 2012; 66:198-200.

36. El-Dakhakhny M, Mady NI, Halim MA. Nigella sativa L. oil protects against induced hepatotoxicity and improves serum lipid profile in rats. Arzneimittelforschung 2000; 50:832-836.

37. Amarouch H, Zaoui A, Cherrah Y, Alaoui K, Mahassini N, Hassar M. Effects of Nigella sativa fixed oil on blood homeostasis in rat. J Ethnopharmacol 2002;79:23-26.

38. Al-Naqeep G, Al-Zubairi AS, Ismail M, Amom ZH, Esa NM. Antiatherogenic potential of Nigella sativa seeds and oil in diet-induced hypercholesterolemia in rabbits. Evid Based Complement Alternat Med 2011; 2011:213628.

39. Nader MA, El-Agamy DS, Suddek GM. Protective effects of propolis and thymoquinone on development of atherosclerosis in cholesterol-fed rabbits. Arch Pharmacal Res 2010; 33:637-643.

40. 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.

41. Zaoui A, Cherrah Y, Alaoui K, Mahassine N, Amarouch H, Hassar M. Effects of Nigella sativa fixed oil on blood homeostasis in rat. J Ethnopharmacol 2002; 79:23-26.

42. Bhatti IU, Rehman FU, 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.

43. Tasawar Z, Siraj Z, Ahmad N, Lashari MH. The effects of Nigelia sativa (Kalonji) on lipid profile in patients with stable coronary artery disease in multan, Pakistan. Pak J Nutr 2011; 10:162.

44. Bamosa AO, Ali B, Sowayan S. Effect of oral ingestion Nigella sativa seeds on some blood parameters. Saudi Pharm J 1997; 5:126-129.

45. Bamosa AO, Ali BA, al-Hawsawi ZA. The effect of thymoquinone on blood lipids in rats. Indian J Physiol pharmacol 2002; 46:195-201.

46. 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: 6684-6688.

47. Sowers JR, Epstein M. Diabetes mellitus and associated hypertension, vascular disease, and nephropathy an update. Hypertension 1995; 26:869-879.

48. Daneman D. Type 1 diabetes. The Lancet 2006; 367:847-858.   

49.  Anonymous. Guidelines N. Anaemia management in people with chronic kidney disease (CKD). Clinical Guidance. N.C.c.f.C. Conditions , London: Royal College of Physicians; 2006. p. 1-172.

50. Stadler K. Oxidative stress in diabetes.  Adv Exp Med Biol 2012; 771:272-287.

51. Shabana A, El-Menyar A, Asim M, Al-Azzeh H, Al Thani H. Cardiovascular benefits of black cumin (Nigella sativa). Cardiovascular Toxicol 2013; 13:9-21.

52. Kanter M, Akpolat M, Aktas C. Protective effects of the volatile oil of Nigella sativa seeds on β-cell damage in streptozotocin-induced diabetic rats: a light and electron microscopic study. J Molecular Histol 2009; 40:379-385.

53. Abdelmeguid NE, Fakhoury R, Kamal SM, Al Wafai RJ. Effects of Nigella sativa and thymoquinone on biochemical and subcellular changes in pancreatic β‐cells of streptozotocin‐induced diabetic rats. J Diabetes 2010; 2:256-266.

54. Kanter M, Coskun O, Korkmaz A, Oter S. Effects of Nigella sativa on oxidative stress and β‐cell damage in streptozotocin‐induced diabetic rats. Anat Rec A Discov Mol Cell Evol Biol 2004; 279:685-691.

55. Rchid H, Chevassus H, Nmila R, Guiral C, Petit P, Chokaïri M, et al. Nigella sativa seed extracts enhance glucose-induced insulin release from rat-isolated Langerhans islets. Fundam Clin Pharmacol 2004; 18:525-529.

56. Al-Hader A, Aqel M, Hasan Z. Hypoglycemic effects of the volatile oil of Nigella sativa seeds. Pharm Biol 1993; 31:96-100.

57. Fararh K, Atoji Y, Shimizu Y, Takewaki T. Isulinotropic properties of Nigella sativa oil in Streptozotocin plus Nicotinamide diabetic hamster. Res Vet Sci 2002; 73:279-282.

58. Kaleem M, Kirmani D, Asif M, Ahmed Q, Bano B. Biochemical effects of Nigella sativa L seeds in diabetic rats. Indian J Exp Biol 2006; 44:745-748.

59. Alenzi F, El-Bolkiny Y-S, Salem M. Protective effects of Nigella sativa oil and thymoquinone against toxicity induced by the anti-cancer drug cyclophosphamide. Br J Biomed Sci 2010; 67:20-28.

60. Hawsawi ZA, Ali BA, Bamosa AO. Effect of Nigella sativa (black seed) and thymoquinone on blood glucose in albino rats. Ann Saudi Med 2001; 21:242-244.

61. Marles RJ, Farnsworth NR. Antidiabetic plants and their active constituents. Phytomedicine 1995; 2:137-189.

62. Abu Khader MM. Thymoquinone: a promising antidiabetic agent. Int J Diabetes Developing Countries 2012; 32:65-8.

63. Salama RH. Hypoglycemic effect of lipoic acid, carnitine and Nigella sativa in diabetic rat model. Int J Health Sci 2011; 5:126-134.

64. Pari L, Sankaranarayanan C. Beneficial effects of thymoquinone on hepatic key enzymes in streptozotocin–nicotinamide induced diabetic rats. Life Sci 2009; 85:830-834.

65. Bamosa AO, Kaatabi H, Lebda FM, Elq A-MA, Al-Sultan A. Effect of Nigella sativa seeds on the glycemic control of patients with type 2 diabetes mellitus. Indian J Physiol Pharmacol 2010; 54:344-354.

66. Sultan MT, Butt MS, Karim R, Zia-Ul-Haq M, Batool R, Ahmad S, et al. Nigella sativa Fixed and Essential Oil Supplementation Modulates Hyperglycemia and Allied Complications in Streptozotocin-Induced Diabetes Mellitus. Evid Based Complement Alternat Med 2014; 2014:826380.

67. Ibrahim RM, Hamdan NS, Mahmud R, Imam MU, Saini SM, Rashid SN, et al. A randomised controlled trial on hypolipidemic effects of Nigella Sativa seeds powder in menopausal women. J Transl Med 2014; 12:82.

68. Sheikh T, Joshi D, Patel B, Modi C. Protective role of Nigella sativa against experimentally induced type-II diabetic nuclear damage in Wistar rats. Veterinary World 2013; 6:698-702.

69. Alam S, Reddy SK, Baig A, Reddy MK, Mohiuddin M, Reddy MV, et al. Evaluation of antidiabetic and anti-lipidimic potential of kalongi sugar powder water extract in stz induced diabetic rats. Int J Pharm Pharm Sci 2013; 5:94-96.

70. 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 Functional Foods 2013; 5:228-234.

71. Ali SA, Asghar F, Nafees M, Tayyab M. Effect of Nigella Sativa (Kalonji) on Serum Lipid Profile. ANNALS 2012; 18:224-228.

72. Nasir A, Siddiqui MY, Mohsin M. Efficacy of Saboos-e-Asapghol (Plantago ovata) and Kalonji (Nigella sativa) in the Management of Hypertriglyceridemia. Int J Pharm India 2013; 2:560-568.

73. Mahmoud MY. Effect of High Protein Diet Containing Fortified Bread with Fenugreek and Nigella sativa Seeds on Rats Suffering from Diabetes. Pak J Nutr 2013; 12:736-747.

74. Shafeeque A. Effects of volatile oil and nonsaponifiable fractions from Nigella sativa oil and it’s constituent, thymoquinone against cardiovascular risk parameters in experimental hyperlipidemia. Indian ETD Repository @ INFLIBNET 2013.

75. Alimohammadi S, Hobbenaghi R, Javanbakht J, Kheradmand D, Mortezaee R, Tavakoli M, et al. Protective and antidiabetic effects of extract from Nigella sativa on blood glucose concentrations against streptozotocin (STZ)-induced diabetic in rats: an experimental study with histopathological evaluation. Diagnostic Pathol 2013; 8:137.

76. Sobhi W, Khettal B, Belmouhoub M, Atmani D, Duez P, Benboubetra M. Hepatotoxicity and Langerhans islets regenerative effects of polar and neutral lipids of Nigella sativa L. in nicotinamide/streptozotocin-induced diabetic rats. Pteridines 2013; 22:97-104.

77. Jamal A, Hmza A, Omar E, Adnan A, Osman MT. Nigella sativa Oil Has Significant Repairing Ability of Damaged Pancreatic Tissue Occurs in Induced Type 1 Diabetes Mellitus. Global J Pharmacol 2013; 7:14-19.

78. Vanhoutte P, Shimokawa H, Tang E, Feletou M. Endothelial dysfunction and vascular disease. Acta Physiologica 2009; 196:193-222.

79. Idris-Khodja N, Schini-Kerth V. Thymoquinone improves aging-related endothelial dysfunction in the rat mesenteric artery. Naunyn Schmiedebergs Arch Pharmacol 2012; 385:749-758.

80. Zaoui A, Cherrah Y, Lacaille-Dubois M, Settaf A, Amarouch H, Hassar M. Diuretic and hypotensive effects of Nigella sativa in the spontaneously hypertensive rat. Therapie 1999; 55:379-82.

81. Demir H, Kanter M, Coskun O, Uz YH, Koc A, Yildiz A. Effect of black cumin (Nigella sativa) on heart rate, some hematological values, and pancreatic β-cell damage in cadmium-treated rats. Biol Trace Elem Res 2006; 110:151-162.

82. El Tahir KE, Ashour MM, Al-Harbi MM. The cardiovascular actions of the volatile oil of the black seed (Nigella sativa) in rats: elucidation of the mechanism of action. Gen Pharmacol 1993; 24:1123-1131.

83. Khattab MM, Nagi MN. Thymoquinone supplementation attenuates hypertension and renal damage in nitric oxide deficient hypertensive rats. Phytother Res 2007; 21:410-414.

84. Meral I, Donmez N, Baydas B, Belge F, Kanter M. Effect of Nigella sativa L. on heart rate and some haematological values of alloxan-induced diabetic rabbits. Scand J Lab Anim Sci 2004; 31:49-53.

85. Dehkordi FR, Kamkhah AF. Antihypertensive effect of Nigella sativa seed extract in patients with mild hypertension. Fundam Clini Pharmacol 2008; 22:447-452.

86. Qidwai W, Hamza HB, Qureshi R, Gilani A. 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. J Altern Complement Med 2009; 15:639-644.

87. American Cancer Society. Cancer Facts and Statistics 2014 [25/4/2014]. Avalible from: research/cancerfactsstatistics/index

88. Servan-Schreiber D. Anti-cancer: a new way of life. J Alternative Complementary Med 2009; 15:805-6.

89. Wang S, Meckling KA, Marcone MF, Kakuda Y, Tsao R. Can phytochemical antioxidant rich foods act as anti-cancer agents? Food Res Int 2011; 44:2545-2554.

90. Wargovich MJ. Anti-cancer properties of fruits and vegetables. HortSci 2000; 35:573-575.

91. 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 2007; 40:839-847.

92. Gali-Muhtasib H, Roessner A, Schneider-Stock R. Thymoquinone: a promising anti-cancer drug from natural sources. Int J Biochem Cell Biol 2006; 38:1249-1253.

93. Rooney S, Ryan M. Effects of alpha-hederin and thymoquinone, constituents of Nigella sativa, on human cancer cell lines. Anticanc Res 2005; 25:2199-2204.

94. Al-Ali A, Alkhawajah AA, Randhawa MA, Shaikh NA. Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats. J Ayub Med Coll Abbottabad 2008; 20:25-27.

95. El-Kadi A, Kandil O, editors. Effects of Nigella sativa (the black seed) on immunity. Proceeding of the 4 th International Conference on Islamic Medicine, Kuwait Bull Islamic Med; 1986.

96. Mabrouk GMMoselhy SSZohny SFAli EMHelal TEAmin AA, et al. Inhibition of methylnitrosourea (MNU) induced oxidative stress and carcinogenesis by orally administered bee honey and Nigella grains in Sprague Dawely rats. J Exp Clinical Canc Res 2002; 21:341-346.

97. Swamy S, Tan B. Cytotoxic and immunopotentiating effects of ethanolic extract of Nigella sativa L. seeds. J Ethnopharmacol 2000; 70:1-7.

98. Kumara SS, Huat BT. Extraction, isolation and characterisation of antitumor principle, α-hederin, from the seeds of Nigella sativa. Planta medica 2001; 67:29-32.

99. 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 Canc Res 2010; 29:87.

100. Bourgou S, Pichette A, Marzouk B, Legault J. Bioactivities of black cumin essential oil and its main terpenes from Tunisia. South Afr J Bot 2010; 76:210-216.

101. Al-Sheddi ES, Farshori NN, Al-Oqail MM, Musarrat J, Al-Khedhairy AA, Siddiqui MA. Cytotoxicity of Nigella Sativa Seed Oil and Extract Against Human Lung Cancer Cell Line. Asian Pacific J Canc Prev 2014; 15:983-987.

102. Globocan. Fact sheet  [27/4/2014]. Available from:

103. Farah IO, Begum RA. Effect of Nigella sativa (N. sativa L.) and oxidative stress on the survival pattern of MCF-7 breast cancer cells. Biomed Sci instrum 2002; 39:359-364.

104. Farah IO. Assessment of cellular responses to oxidative stress using MCF-7 breast cancer cells, black seed (N. Sativa L.) extracts and H2O2. Int J Envir Res  Publ Health  2005; 2:411-419.

105. El‐Aziz MA, Hassan HA, Mohamed MH, Meki AR, Abdel‐Ghaffar SK, Hussein MR. The biochemical and morphological alterations following administration of melatonin, retinoic acid and Nigella sativa in mammary carcinoma: an animal model. Int J Exp pathol 2005; 86:383-396.

106. Effenberger K, Breyer S, Schobert R. Terpene Conjugates of the Nigella sativa Seed‐Oil Constituent Thymoquinone with Enhanced Efficacy in Cancer Cells. Chem biodivers 2010; 7:129-139.

107. Baharetha HM, Nassar ZD, Aisha AF, Ahamed MB, Al-Suede FS, Kadir MO, et al. Proapoptotic and Antimetastatic Properties of Supercritical CO2 Extract of Nigella sativa Linn. Against Breast Cancer Cells. J Med Food 2013; 16:1121-1130.

108. Salim EI, Fukushima S. Chemopreventive potential of volatile oil from black cumin (Nigella sativa L.) seeds against rat colon carcinogenesis. Nutr Canc 2003; 45:195-202.

109. Gali-Muhtasib H, Diab-Assaf M, Boltze C, Al-Hmaira J, Hartig R, Roessner A, et al. Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism. Int J Oncol 2004; 25:857-866.

110. Rooney S, Ryan M. Modes of action of alpha-hederin and thymoquinone, active constituents of Nigella sativa, against HEp-2 cancer cells. Anticanc Res 2005; 25:4255-4259.

111. Khan N, Sultana S. Inhibition of two stage renal carcinogenesis, oxidative damage and hyperproliferative response by Nigella sativa. Eur J Canc Prev 2005; 14:159-168.

112. Tabasi N, Mahmoudi M, Rastin M, Sadeghnia HR, HosseinPour Mashhadi M, Zamani Taghizade Rabe S, et al. Cytotoxic and apoptogenic properties of Nigella sativa and thymoquinone, its constituent, in human renal cell carcinoma are comparable with cisplatin. Food Agric Immunol 2015; 26:138-156.

113. Iddamaldeniya SS, Wickramasinghe N, Thabrew               I, Ratnatunge N, Thammitiyagodage MG.                     Protection against diethylnitrosoamine-induced hepatocarcinogenesis by an indigenous medicine comprised of Nigella sativa, Hemidesmus indicus and Smilax glabra: a preliminary study. J Carcinogenesis 2003; 2:1-6.

114. Iddamaldeniya SS, Thabrew M, Wickramasinghe S, Ratnatunge N, Thammitiyagodage MG. A long-term investigation of the anti-hepatocarcinogenic potential of an indigenous medicine comprised of Nigella sativa, Hemidesmus indicus and Smilax glabra. J Carcinogenesis 2006; 5:1-7.

115. Thabrew MI, Mitry RR, Morsy MA, Hughes RD. Cytotoxic effects of a decoction of Nigella sativa, Hemidesmus indicus and Smilax glabra on human hepatoma HepG2 cells. Life Sci 2005; 77:1319-1330.

116. Samarakoon SR, Thabrew I, Galhena PB, De Silva D, Tennekoon KH. A comparison of the cytotoxic potential of standardized aqueous and ethanolic extracts of a polyherbal mixture comprised of Nigella sativa (seeds), Hemidesmus indicus (roots) and Smilax glabra (rhizome). Pharmacognosy Res 2010; 2:335-342.

117. Salomi MJ, Nair SC, Panikkar KR. Inhibitory effects of Nigella sativa and saffron (Crocus sativus) on chemical carcinogenesis in mice. Nutr Canc 1991; 16:67-72.

118. Chehl N, Chipitsyna G, Gong Q, Yeo CJ, Arafat HA. Anti‐inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells. HPB 2009; 11:373-381.

119. 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. Canc Res 2009; 69:5575-5583.

120. Torres MP, Ponnusamy MP, Chakraborty S, Smith LM, Das S, Arafat HA, et al. Effects of thymoquinone in the expression of mucin 4 in pancreatic cancer cells: implications for the development of novel cancer therapies. Mol Canc Therapeutics 2010; 9:1419-1431.

121. Shafi G, Munshi A, Hasan TN, Alshatwi AA, Jyothy A, Lei DK. Induction of apoptosis in HeLa cells by chloroform fraction of seed extracts of Nigella sativa. Cancer Cell Int 2009; 9:29.

122. Hasan TN, Shafi G, Syed NA, Alfawaz MA, Alsaif MA, Munshi A, et al. Methanolic extract of Nigella sativa seed inhibits SiHa human cervical cancer cell proliferation through apoptosis. Natur Prod Commun 2013; 8:213-216.

123. Salomi N, Nair S, Jayawardhanan K, Varghese C, Panikkar K. Antitumour principles from Nigella sativa seeds. Canc Lett 1992; 63:41-46.

124. Worthen DR, Ghosheh OA, Crooks P. The in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa L. Anticanc Res 1997; 18:1527-1532.

125. Badary O, AI-Shabanah O, Nagi M, AI-Rikabi A, Elmazar M. Inhibition of benzo (a) pyrene-induced forestomach carcinogenesis in mice by thymoquinone. Eur J Canc Prev 1999; 8:435-440.

126. Badary OA, El-Din AMG. Inhibitory effects of thymoquinone against 20-methylcholanthrene-induced fibrosarcoma tumorigenesis. Canc Detect Prev 2001; 25:362-368.

127. Norwood A, Tucci M, Benghuzzi H. A comparison of 5-fluorouracil and natural chemotherapeutic agents, EGCG and thymoquinone, delivered by sustained drug delivery on colon cancer cells. Biomed Sci Instrum 2006; 43:272-277.

128. Norwood A, Tan M, May M, Tucci M, Benghuzzi H. Comparison of potential chemotherapeutic agents, 5-fluoruracil, green tea, and thymoquinone on colon cancer cells. Biomed Sci Instrum 2005; 42:350-356.

129. 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 Canc 2005; 117:409-417.

130. Ahmed WA, Hassan SA, Galeb FM, El-Taweel MA, Abu-Bedair FA. The in vitro promising therapeutic activity of thymoquinone on hepatocellular carcinoma (HepG2) cell line. Global Veterinaria 2008; 2:233-241.

131. Hassan S, Ahmed W, M.Galeb F, El-Taweel M, A.Abu-Bedair f. In vitro challenge using thymoquinone on hepatocellular carcinoma (HepG2) cell line. Iran J Pharm Res 2010; 7:283-90.

132. El-Najjar N, Chatila M, Moukadem H, Vuorela H, Ocker M, Gandesiri M, et al. Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling. Apoptosis 2010; 15:183-195.

133. Salomi M, Nair SC, Panikkar K. Inhibitory effects of Nigella sativa and saffron (Crocus sativus) on chemical carcinogenesis in mice. Nutr Cancer 1991; 16:67-72.

134. Kaseb AO, Chinnakannu K, Chen D, Sivanandam A, Tejwani S, Menon M, et al. Androgen receptor–and E2F-1–targeted thymoquinone therapy for hormone-refractory prostate cancer. Canc Res 2007; 67:7782-7788.

135. Koka PS, Mondal D, Schultz M, Abdel-Mageed AB, Agrawal KC. Studies on molecular mechanisms of growth inhibitory effects of thymoquinone against prostate cancer cells: role of reactive oxygen species. Exp Biol Med 2010; 235:751-760.

136. Yi T, Cho S-G, Yi Z, Pang X, Rodriguez M, Wang Y, et al. Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways. Mol Canc Therapeutics 2008; 7:1789-1796.

137. Xuan NT, Shumilina E, Qadri SM, Goetz F, Lang F. Effect of thymoquinone on mouse dendritic cells. Cellular Physiol Biochem 2010; 25:307-314.

138. Sethi G, Ahn KS, Aggarwal BB. Targeting nuclear factor-κB activation pathway by thymoquinone: role in suppression of antiapoptotic gene products and enhancement of apoptosis. Mol Canc Res 2008; 6:1059-1070.

139. Ismail M, Al-Naqeep G, Chan KW. Nigella sativa thymoquinone-rich fraction greatly improves plasma antioxidant capacity and expression of antioxidant genes in hypercholesterolemic rats. Free Radical Biol Med 2010; 48:664-672.

140. Ebru U, Burak U, Yusuf S, Reyhan B, Arif K, Faruk TH, et al. Cardioprotective effects of Nigella sativa oil on cyclosporine A‐induced cardiotoxicity in rats. Basic Clin Pharmacol Toxicol 2008; 103:574-580.

141. Barron J, Benghuzzi H, Tucci M. Effects of thymoquinone and selenium on the proliferation of mg 63 cells in tissue culture. Biomed Sci Instrum 2007; 44:434-440.

142.  Bawadi H. A, Bansode R. R, Losso J. N. Thymoquinone in the control of hypoxia-induced angiogenic disease biomarkers: Insight into the mechanism of action in vitro, IFT Annual Meeting 2004; Las Vegas NV USA ,  2004: 7-8

143. Swamy SMHuat BT. Intracellular glutathione depletion and reactive oxygen species generation are important in α-hederin-induced apoptosis of P388 cells. Mol Cell Biochem 2003; 245:127-139.