Thymoquinone: an emerging natural drug with a wide range of medical applications

Document Type : Review Article


1 Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Arab American University- Jenin, Jenin, Palestine

2 Division of Genetics, Department of Cell Biology, University of Salzburg, Hellbrunnerstrasse 34, A-5020 Salzburg, Austria


Nigella sativa has attracted healers in ancient civilizations and researchers in recent times. Traditionally, it has been used in different forms to treat many diseases including asthma, hypertension, diabetes, inflammation, cough, bronchitis, headache, eczema, fever, dizziness and influenza. Experimentally, it has been demonstrated that N. sativa extracts and the main constituent of their volatile oil, thymoquinone, possess antioxidant, anti-inflammatory and hepatoprotective properties. In this review we aimed at summarizing the most recent investigations related to a few and most important effects of thymoquinone. It is concluded that thymoquinone has evidently proved its activity as hepatoprotective, anti-inflammatory, antioxidant, cytotoxic and anti-cancer chemical, with specific mechanisms of action, which provide support to consider this compound as an emerging drug.  Further research is required to make thymoquinone a pharmaceutical preparation ready for clinical trials.


1. Ali BH, Blunden G. Pharmacological and toxicological properties of Nigella sativa. Phytother Res 2003; 17:299-305.
2. Entok E, Ustuner MC, Ozbayer C, Tekin N, Akyuz F, Yangi B, et al. Anti-inflammatuar and anti-oxidative effects of Nigella sativa L.: FDG-PET imaging of inflammation. Mol Biol Rep 2014; 41:2827-2834.
3. Jazieh AR, Al Sudairy R, Abulkhair O, Alaskar A, Al Safi F, Sheblaq N, et al. Use of complementary and alternative medicine by patients with cancer in Saudi Arabia. J Altern Complement Med 2012; 8:1045- 1049.
4. Mayadagli A, Aksu A, Goksel F, Gocen E, Karahacioglu E, Gumus M, et al. Determination of parameters affecting the use of complementary and alternative medicine in cancer patients and detection of prevalence of use. Afr J Tradit Complement Altern Med 2011; 8:477-482.
5. Soleimani H, Ranjbar A, Baeeri M, Mohammadirad A, Khorasani R, Yasa N, et al. Rat plasma oxidation status after Nigella sativa L. botanical treatment in CCL(4)-treated rats. Toxicol Mech Methods 2008; 18:725-731.
6. Abdel-Wahhab MA, Aly SE. Antioxidant property of Nigella sativa (black cumin) and Syzygium aromaticum (clove) in rats during aflatoxicosis. J Appl Toxicol 2005; 25:218-223.
7. Ashraf SS, Rao MV, Kaneez FS, Qadri S, Al-Marzouqi AH, Chandranath IS, et al. Nigella sativa extract as a potent antioxidant for petrochemical-induced oxidative stress. J Chromatogr Sci 2011; 49:321-326.
8. El-Dakhakhny M, Madi NJ, 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.
9. Hajhashemi V, Ghannadi A, Jafarabadi H. Black cumin seed essential oil, as a potent analgesic and antiinflammatory drug. Phytother Res 2004; 18:195-199.
10. Bakathir HA, Abbas NA. Detection of the antibacterial effect of Nigella sativa ground seeds with water. Afr J Tradit Complement Altern Med 2011; 8: 159-164.
11. Chaieb K, Kouidhi B, Jrah H, Mahdouani K, Bakhrouf A. Antibacterial activity of Thymoquinone, an active principle of Nigella sativa and its potency to prevent bacterial biofilm formation. BMC Complement Altern Med 2011; 11:29.
12. Kokoska L, Havlik J, Valterova I, Sovova H, Sajfrtova M, Jankovska I. Comparison of chemical composition and antibacterial activity of Nigella sativa seed essential oils obtained by different extraction methods. J Food Prot 2008; 71:2475-2480.
13. Al-Suhaimi EA. Hepatoprotective and immunological functions of Nigella sativa seed oil against hypervitaminosis A in adult male rats. Int J Vitam Nutr Res 2012; 82:288-297.
14. Daba MH, Abdel-Rahman MS. Hepatoprotective activity of thymoquinone in isolated rat hepatocytes. Toxicol Lett 1998; 95:23-29.
15. Hassan AS, Ahmed JH, Al-Haroon SS. A study of the effect of Nigella sativa (Black seeds) in isoniazid (INH)-induced hepatotoxicity in rabbits. Indian J Pharmacol 2012; 44:678-682.
16. Michel CG, El-Sayed NS, Moustafa SF, Ezzat SM, Nesseem DI, El-Alfy TS. Phytochemical and biological investigation of the extracts of Nigella sativa L. seed waste. Drug Test Anal 2011; 3:245-254.
17. Talib WH, Abukhader MM. Combinatorial effects of thymoquinone on the anti-cancer activity and hepatotoxicity of the prodrug CB 1954. Sci Pharm 2013; 81:519-530.
18. 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.
19. Khader M, Bresgen N, Eckl PM. Antimutagenic effects of ethanolic extracts from selected Palestinian medicinal plants. J Ethnopharmacol 2010; 127:319-324.
20. Aikemu A, Xiaerfuding X, Shiwenhui C, Abudureyimu M, Maimaitiyiming D. Immunomodulatory and anti-tumor effects of Nigella glandulifera freyn and sint seeds on ehrlich ascites carcinoma in mouse model. Pharmacogn Mag 2013; 9:187-191.
21. Arafa e, Zhu Q, Shah ZI, Wani G, Barakat BM, Racoma I, et al. Thymoquinone up-regulates PTEN expression and induces apoptosis in doxorubicin-resistant human breast cancer cells. Mutat Res 2011; 706:28-35.
22. Majdalawieh AF, Hmaidan R, Carr RI. Nigella sativa modulates splenocyte proliferation, Th1/Th2 cytokine profile, macrophage function and NK anti-tumor activity. J Ethnopharmacol 2010; 131:268-275.
23. Aycan IO, Tufek A, Tokgoz O, Evliyaoglu O, Firat U, Kavak GO, et al. Thymoquinone treatment against acetaminophen-induced hepatotoxicity in rats. Int J Surg 2014; 12:213-218.
24. Nagi MN, Almakki HA, Sayed-Ahmed MM, Al-Bekairi AM. Thymoquinone supplementation reverses acetaminophen-induced oxidative stress, nitric oxide production and energy decline in mice liver. Food Chem Toxicol 2010; 48:2361-2365.
25. Talib WH, Abukhader MM. Combinatorial effects of thymoquinone on the anti-cancer activity and hepatotoxicity of the prodrug CB 1954. Sci Pharm 2013; 81:519-530.
26. El-Sayed WM. Upregulation of chemoprotective enzymes and glutathione by Nigella sativa (black seed) and thymoquinone in CCl4-intoxicated rats. Int J Toxicol 2011; 30:707-714.
27. Helal GK. Thymoquinone supplementation ameliorates acute endotoxemia-induced liver dysfunction in rats. Pak J Pharm Sci 2010; 23:131-137.
28. Khader M, Bresgen N, Eckl PM. In vitro toxicological properties of thymoquinone. Food Chem Toxicol 2009; 47:129-133.
29. Babazadeh B, Sadeghnia HR, Safarpour Kapurchal E, Parsaee H, Nasri S, Tayarani-Najaran Z. Protective effect of Nigella sativa and thymoquinone on serum/glucose deprivation-induced DNA damage in PC12 cells. Avicenna J Phytomed 2012; 2:125-132.
30. Kundu J, Kim DH, Kundu JK, Chun KS. Thymoquinone induces heme oxygenase-1 expression in HaCaT cells via Nrf2/ARE activation: Akt and AMPKalpha as upstream targets. Food Chem Toxicol 2014; 65:18-26.
31. Rifaioglu MM, Nacar A, Yuksel R, Yonden Z, Karcioglu M, Zorba OU, et al. Antioxidative and anti-inflammatory effect of thymoquinone in an acute Pseudomonas prostatitis rat model. Urol Int 2013; 91:474-481.
32. Alemi M, Sabouni F, Sanjarian F, Haghbeen K, Ansari S. Anti-inflammatory effect of seeds and callus of Nigella sativa L. extracts on mix glial cells with regard to their thymoquinone content. AAPS Pharm Sci Tech 2013;14:160-167.
33. Lei X, Liu M, Yang Z, Ji M, Guo X, Dong W. Thymoquinone prevents and ameliorates dextran sulfate sodium-induced colitis in mice. Dig Dis Sci 2012; 57:2296-2303.
34. Yang W, Bhandaru M, Pasham V, Bobbala D, Zelenak C, Jilani K et al. Effect of thymoquinone on cytosolic pH and Na+/H+ exchanger activity in mouse dendritic cells. Cell Physiol Biochem 2012; 29:21-30.
35. Woo CC, Kumar AP, Sethi G, Tan KH. Thymoquinon: potential cure for inflammatory disorders and cancer. Biochem Pharmacol 2012; 83:443-451.
36. 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 (Oxford) 2009; 11:373-381.
37. Bai T, Yang Y, Wu YL, Jiang S, Lee JJ, Lian LH, et al. Thymoquinone alleviates thioacetamide-induced hepatic fibrosis and inflammation by activating LKB1-AMPK signaling pathway in mice. Int Immunopharmacol 2014; 19:351-357.
38. Kundu JK, Liu L, Shin JW, Surh YJ. Thymoquinone inhibits phorbol ester-induced activation of NF-kappaB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo. Biochem Biophys Res Commun 2013; 438:721-727.
39. Al Wafai RJ. Nigella sativa and thymoquinone suppress cyclooxygenase-2 and oxidative stress in pancreatic tissue of streptozotocin-induced diabetic rats. Pancreas 2013; 42:841-849.
40. Kanter M, Demir H, Karakaya C, Ozbek H. Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats. World J Gastroenterol 2005; 11:6662-6666.
41. Kanter M, Coskun O, Uysal H. The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage. Arch Toxicol 2006; 80:217-224.
42. 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.
43. Nemmar A, Al-Salam S, Zia S, Marzouqi F, Al-Dhaheri A, Subramaniyan D, et al. Contrasting actions of diesel exhaust particles on the pulmonary and cardiovascular systems and the effects of thymoquinone. Br J Pharmacol 2011; 164:1871-1882.
44. El Gazzer M, El Mezayen R, Nicolls MR, Marecki JC, Dreskin SC. Down-regulation of leukotriene biosynthesis by thymoquinone attenuates airway inflammation in a mouse model of allergic asthma. Biochim Biophys Acta 2006; 1760:1088-1095.
45. Ammar El-SM, Gameil NM, Shawky NM, Nader MA. Comparative evaluation of anti-inflammatory properties of thymoquinone and curcumin using an asthmatic murine model. Int Immunopharmacol 2011; 11:2232-2236.
46. Boskabady MH, Kiani S, Jandaghi P, Ziaei T, Zarei A. Antitussive effect of Nigella Sativa in Guinea Pigs. Pak J Med Sci 2004; 20:224-228.
47. Keyhanmanesh R, Boskabady MH, Khamneh S, Doostar Y. Effect of thymoquinone on the lung pathology and cytokine levels of ovalbumin-sensitized guinea pigs. Pharmacological Reports 2010; 62:910-916.
48. Keyhanmanesh R, Boskabady MH, Eslamizadeh MJ, Khamneh S, Ebrahimi MA. The effect of thymoquinone, the main constituent of Nigella sativa on tracheal responsiveness and white blood cell count in lung lavage of sensitized guinea pigs. Planta Medica 2010; 76:218-222.
49. Boskabady MH, Keyhanmanesh R, Khameneh S, Doostdar Y, Khakzad MR. Potential immunomodulation effect of the extract of Nigella sativa on ovalbumin sensitized guinea pigs. J Zhejiang Univ-Sci B 2011; 12:201-209.
50. Boskabady MH, Vahedi N, Amery S, Khakzad MR. The effect of Nigella sativa alone, and in combination with dexamethasone, on tracheal muscle responsiveness and lung inflammation in sulfur mustard exposed guinea pigs. J Ethnopharmacol. 2011; 137:1028-1034.
51. Keyhanmanesh R, Boskabady MH, Ebrahimi Saadatloo MA, Khamnei S. The contribution of water and lipid soluble substances in the relaxant effects of Nigella sativa extract on guinea pig tracheal smooth muscle (in vitro). Iran J Basic Med Sci 2007; 10:154-161.
52. Al-Majed AA, Al-Omar FA, Nagi MN. Neuroprotective effects of thymoquinone against transient forebrain ischemia in the rat hippocampus. Eur J Pharmacol 2006; 543:40-47.
53. Hosseinzadeh H, Parvardeh S, Asl MN, Sadeghnia HR, Ziaee T. Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperfusion injury in rat hippocampus. Phytomedicine 2007; 14:621-627
54. Nili-Ahmadabadi A, Tavakoli F, Hasanzadeh G, Rahimi H, Sabzevari O. Protective effect of pretreatment with thymoquinone against Aflatoxin B(1) induced liver toxicity in mice. Daru 2011; 19:282-287.
55. Ahlatci A, Kuzhan A, Taysi S, Demirtas OC, Alkis HE, Tarakcioglu M, et al. Radiation-modifying abilities of Nigella sativa and thymoquinone on radiation-induced nitrosative stress in the brain tissue. Phytomedicine 2014; 21:740-744.
56. Khan N, Sultana S. Inhibition of two stage                renal carcinogenesis, oxidative damage and hyperproliferative response by Nigella sativa. Eur J of Cancer Prev 2005; 1:159-168.
57. Khan MA, Anwar S, Aljarbou AN, Al-Orainy M, Aldebasi YH, Islam S, et al. Protective effect of thymoquinone on glucose or methylglyoxal-induced glycation of superoxide dismutase. Int J Biol Macromol 2014; 65:16-20.
58. Harzallah HJ, Grayaa R, Kharoubi W, Maaloul A, Hammami M, Mahjoub T. Thymoquinone, the Nigella sativa bioactive compound, prevents circulatory oxidative stress caused by 1, 2-dimethylhydrazine in erythrocyte during colon postinitiation carcinogenesis. Oxid Med Cell Longev 2012; 2012:854065.
59. Alenzi FQ, El-Bolkiny Y, Salem ML. 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. Alhebshi AH, Gotoh M, Suzuki I. Thymoquinone protects cultured rat primary neurons against amyloid beta-induced neurotoxicity. Biochem Biophys Res Commun 2013; 433:362-367.
61. 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.
62. Ulasli SS, Celik S, Gunay E, Ozdemir M, Hazman O, Ozyurek A, et al. Anti-cancer effects of thymoquinone, caffeic acid phenethyl ester and resveratrol on A549 non-small cell lung cancer cells exposed to benzo(a)pyrene. Asian Pac J Cancer Prev 2013; 14:6159-6164.
63. Woo CC, Loo SY, Gee V, Yap CW, Sethi G, Kumar AP,  et al. Anti-cancer activity of thymoquinone in breast cancer cells: possible involvement of PPAR-gamma pathway. Biochem Pharmacol 2011; 82:464-475.
64. Woo CC, Hsu A, Kumar AP, Sethi G, Tan KH. Thymoquinone inhibits tumor growth and induces apoptosis in a breast cancer xenograft mouse model: the role of p38 MAPK and ROS. PLoS One 2013; 8:e75356.
65. Xu D, Ma Y, Zhao B, Li S, Zhang Y, Pan S, et al. Thymoquinone induces G2/M arrest, inactivates PI3K/Akt and nuclear factor-kappaB pathways in human cholangiocarcinomas both in vitro and in vivo. Oncol Rep 2014; 31:2063-2070.
66. Ahmad I, Muneer KM, Tamimi IA, Chang ME, Ata MO, Yusuf N. Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome. Toxicol Appl Pharmacol 2013; 270:70-76.
67. Acharya BR, Chatterjee A, Ganguli A, Bhattacharya S, Chakrabarti G. Thymoquinone inhibits microtubule polymerization by tubulin binding and causes mitotic arrest following apoptosis in A549 cells. Biochimie 2014; 97:78-91.
68. Alhosin M, Ibrahim A, Boukhari A, Sharif T, Gies JP, Augr C, et al. Anti-neoplastic agent thymoquinone induces degradation of alpha and beta tubulin proteins in human cancer cells without affecting their level in normal human fibroblasts. Invest New Drugs 2012; 30:1813-1819.
69. Ashley RE, Osheroff N. Natural products as topoisomerase II poisons: effects of thymoquinone on DNA cleavage mediated by human topoisomerase II alpha. Chem Res Toxicol 2014; 27:787-793.
70. Racoma IO, Meisen WH, Wang QE, Kaur B, Wani AA. Thymoquinone inhibits autophagy and induces cathepsin-mediated, caspase-independent cell death in glioblastoma cells. PLoS One 2013; 8:e72882.
71. Paramasivam A, Sambantham S, Shabnam J, Raghunandhakumar S, Anandan B, Rajiv R, et al. Anti-cancer effects of thymoquinone in mouse neuroblastoma (Neuro2-a) cells through caspase-3 activation with down-regulation of XIAP. Toxicol Lett 2012; 213:151-159.
72. Sutton KM, Greenshields AL, Hoskin DW. Thymoquinone, A bioactive component of black caraway seeds, causes G1 phase cell cycle arrest and apoptosis in triple-negative breast cancer cells with mutant p53. Nutr Cancer 2014, 66:408-418.
73. Siveen KS, Mustafa N, Li F, Kannaiyan R, Ahn KS, Kumar AP, et al. Thymoquinone overcomes chemoresistance and enhances the anti-cancer effects of bortezomib through abrogation of NF-kappaB regulated gene products in multiple myeloma xenograft mouse model. Oncotarget 2014; 5:634-648.
74. Ashour AE, Abd-Allah AR, Korashy HM, Attia SM, Alzahrani AZ, Saquib Q, et al. Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis. Mol Cell Biochem 2014; 389:85-98.