셀메드 (CELLMED)

  • 제10권2호
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  • Pages.11.1-11.14
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  • 2020
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  • 3022-6805(pISSN)
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  • 3022-6791(eISSN)
셀메드 세포교정의약학회 (Cellmed Orthocellular Medicine and Pharmaceutical Association)
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A Review On Nigella sativa (Kalonji) Seeds: A Universal Healer

  • 투고 : 2020.01.09
  • 심사 : 2020.03.05
  • 발행 : 2020.05.29
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⟨ 이전 논문 다음 논문 ⟩

초록

Nigella sativa commonly known as Black seed, Black cumin or Kalonji (Family Ranunculaceae) is a widely used for its miraculous healing power. Use of N. sativa seeds and oil has splendid historical past in diverse traditional systems of medicine and food. In Tibb-e-Nabwi (Prophetic Medicine), it is considered as one of the greatest forms of healing medicine. Phytochemically; it contains fixed oil, protein, alkaloids saponin and essential oil. Therapeutic properties of this plant are due to the presence of thymoquinone which is one of major active component and has different beneficial properties. In Unani System of Medicine the diseases are treated with nontoxic herbal drugs. As per Unani classical literature N. sativa perform various pharmacological actions like carminative, anti-inflammatory, analgesic, diuretic, emmenagogue, galactagogue, expectorant etc. Ample of phytochemical, pharmacological and clinical researches has been executed on N. sativa., which may include antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, anti-inflammatory, bronchodilator, hepato-protective, renal protective, gastro-protective, antioxidant properties, etc. This review is an effort to summarize the literature on scientific researches of pharmacognostical characteristics, chemical composition and pharmacological activities of the kalonji seeds

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참고문헌

  1. Abdelrazek HMA, Kilany OE, Muhammad MAA, Tag HM, Abdelazim AM. Black Seed Thymoquinone Improved Insulin Secretion, Hepatic Glycogen Storage, and Oxidative Stress in Streptozotocin-Induced Diabetic Male Wistar Rats. Oxidative Medicine and Cellular Longevity Volume, pp.1-10, 2018
  2. Abdel-Zaher AO, Abdel-Rahman MS, Elwasei FM. Protective effect of Nigella sativa oil against tramadol-induced tolerance and dependence in mice: role of nitric oxide and oxidative stress. Neurotoxicology, 2011;32(6):725-733 https://doi.org/10.1016/j.neuro.2011.08.001
  3. Abel-Salam BK. Immunomodulatory effects of black seeds and garlic on alloxan-induced diabetes in albino rat. Allergologica et Immunopathological, 2012;40(6):336-340. https://doi.org/10.1016/j.aller.2011.07.002
  4. Abououf EA, Elhamshary AMS, Nagati IM, Eraky MA, Elkholy AA, Ibrahim AN, Omar GH. Effect Of Nigella sativa Oil On Schistosoma Mansoni Mature Worms In Experimentally Infected Mice. Journal of the Egyptian Society of Parasitology, 2018; 48(1): 55-66 https://doi.org/10.21608/jesp.2018.77023
  5. Abul-Nasr SM, El-Shafey MDM, Osfor MMH. Amelioration by Nigella sativa of methotrexate induced toxicity in male albino rats: a biochemical, haematological and histological study. Scintia Agriculturae Bohemica, 2001;32:123-160.
  6. Aftab A, Yousaf Z, Javaid A, Riaz N, Younas A, Rashid M, Shamsheer HB, Chahel AA. Antifungal Activity of Vegetative Methanolic Extracts of Nigella sativa against Fusarium oxysporum and Macrophomina phaseolina and its Phytochemical Profiling by GC-MS Analysis. International journal of agriculture & biology, 2019; 21: 569-576
  7. Agarwal C, Narula A, Vyas DK, Jacob D. Effect of seeds of kalaunji on fertility and sialic acid content of the reproductive organs of male rat. Geo Bios, 1990;17:269-272.
  8. Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Zoheir A, Damanhouri ZA, Anwar F. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pacific Journal of Tropical Biomedicine, 2013;3(5): 337-352 https://doi.org/10.1016/S2221-1691(13)60075-1
  9. AI-Jassir SM. Chemical composition and microflora of black cumin (Nigella sativa L.) seeds growing in Saudi Arabia. Food Chemistry, 1992;45: 239-242 https://doi.org/10.1016/0308-8146(92)90153-S
  10. Akhtar M, Maikiyo AM, Khanam R, Mujeeb M, Aqil M, Najmi AK. Ameliorating effects of two extracts of Nigella sativa in middle cerebral artery occluded rat. Journal of Pharmacy and Bioallied Science, 2012;4(1):70-75. https://doi.org/10.4103/0975-7406.92740
  11. Aklaque N, Begum W. Therapeutic & pharmacological potential of Nigella sativa linn. In unani system of medicine: a review. World Journal of Pharmaceutical Research, 2018;7(12):153-158
  12. Al Mofleh IA, Alhaider AA, Mossa JS, Al-Sohaibani MO, Al-Yahya MA, Rafatullah S, et al. et al. Gastroprotective effect of an aqueous suspension of black cumin Nigella sativa on necrotizing agents-induced gastric injury in experimental animals. Saudi Journal of Gastroenterology, 2008;14(3):128-134. https://doi.org/10.4103/1319-3767.41731
  13. 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. Journal of Ayub Medical College Abbottabad, 2008;20(2):25-27.
  14. Alemi M, Sabouni F, Sanjarian F, Haghbeen K, Ansari S. Antiinflammatory effect of seeds and callus of Nigella sativa L. extracts on mix glial cells with regard to their thymoquinone content. AAPS Pharm Sci Tech, 2012
  15. Al-Ghamdi MS. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. Journal of Ethnopharmacology, 2001;76:45-48 https://doi.org/10.1016/S0378-8741(01)00216-1
  16. Ali BH. The effect of Nigella sativa oil on gentamicin nephrotoxicity in rats. American Journal of Chinese Medicine, 2004;32(1):49-55 https://doi.org/10.1142/S0192415X04001710
  17. Aljabre SH, Randhawa MA, Akhtar N, Alakloby OM, Alqurashi AM, Aldossary A. Antidermatophyte activity of ether extract of Nigella sativa and its active principle, thymoquinone. Journal of Ethnopharmacology, 2005; 101(1-3): 116-119. https://doi.org/10.1016/j.jep.2005.04.002
  18. Al-Naggar TB, Gomez-Serranillos MP, Carretero ME, Villar AM. Neuropharmacological activity of Nigella sativa L. extracts. Journal of Ethnopharmacology, 2003;88(1):63-68. https://doi.org/10.1016/S0378-8741(03)00157-0
  19. Al-Othman A M, Ahmad F, Al-Orf S, Al-Murshed KS, Ariff Z. Effect of dietary supplementation of Ellataria cardamun and Nigella sativa on the toxicity of rancid corn oil in rats. International Journal of Pharmocology, 2006; 2(1): 60-65. https://doi.org/10.3923/ijp.2006.60.65
  20. Altan MF, Kanter M, Donmez S, Kartal ME, Buyukbas S. Combination therapy Nigella sativa and human parathyroid hormone on bone mass, biomechanical behavior and structure in streptozotocin-induced diabetic rats. Acta Histochemica, 2007;109(4):304-314. https://doi.org/10.1016/j.acthis.2007.02.006
  21. Althnaian T, Albokhadaim I, El-Bahr SM. Hepatic Gene Expression, Antioxidant Enzymes and Anti-diabetic Effect of Nigella sativa in Diabetic Rats. International Journal of Pharmacology, 2019; 15(2): 265-273. https://doi.org/10.3923/ijp.2019.265.273
  22. Andaloussi AB, Martineau LC, Spoor D, Vuong T, Leduc C, Joly E, Burt A, Meddah B, Settaf A, Arnason JT, Prentki M, Haddad PS. Antidiabetic Activity of Nigella sativa. Seed Extract in Cultured Pancreatic ${\beta}$-cells, Skeletal Muscle Cells, and Adipocytes. Pharmaceutical Biology, 2008;46(1-2): 96-104. https://doi.org/10.1080/13880200701734810
  23. Andaloussi AB, Martineau L, Vuong T, Meddah B, Madiraju P, Settaf A, Haddad PS. 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, 2011; 2011:538671.
  24. Anonymous. Standardization of Single Drugs Of Unani Medicine. CCRUM, 1992; II:196-200
  25. Anonymous. The Unani Pharmacopoeia Of India (First Edition) .Ministry Of Health & Family Welfare Government Of India. YNM
  26. Aqel M, Shaheen R. Effects of the volatile oil of Nigella sativa seeds on the uterine smooth muscle of rat and guinea pig. Journal of Ethnopharmacy, 1996;52(1):23-26. https://doi.org/10.1016/0378-8741(95)01330-X
  27. Arefin Z, Hossain MN, Rahmatullah M. Oral glucose tolerance test (OGTT) with a polyherbal formulation of Nigella sativa and Brassica alba seeds. World Journal of Pharmaceutical Research, 2018;7(13):1200-1206
  28. Askari G, Rouhani MH, Ghaedi E, Ghavami A, Nouri M, Mohammadi H. Effect of Nigella sativa (black seed) supplementation on glycemic control: A systematic review and meta-analysis of clinical trials. Phytotherapy Research, 2019;33(5):1341-1352 https://doi.org/10.1002/ptr.6337
  29. Assayed ME. Radioprotective effects of black seed (Nigella sativa) oil against hemopoietic damage and immunosuppression in gamma-irradiated rats. Immunopharmacology and Immunotoxicology, 2010;32(2):284-296. https://doi.org/10.3109/08923970903307552
  30. Bakathir HA, Abbas NA. Detection of the antibacterial effect of Nigella sativa ground seeds with water. African Journal of Traditional, Complementary and Alternative Medicine, 2011; 8(2): 159-164
  31. Bamosa AO, Kaatabi H, Lebdaa FM, Elq AM, Al-Sultanb A. Effect of Nigella sativa seeds on the glycemic control of patients with type 2 diabetes mellitus. Indian Journal of Physiology and Pharmacology, 2010; 54(4):344-354.
  32. Bodaghi MN, Darabi Z, Agah S, Hekmatdoost A. The effects of Nigella sativa on quality of life, disease activity index, and some of inflammatory and oxidative stress factors in patients with ulcerative colitis. Phytotherapy Research, pp.1-6, 2009
  33. Boskabady MH, Javan H, Sajady M, Rakhshandeh H. The possible prophylactic effect of Nigella sativa seed extract in asthmatic patients. Fundamental and Clinical Pharmacology, 2007;21(5):559-566. https://doi.org/10.1111/j.1472-8206.2007.00509.x
  34. Boskabady MH, Keyhanmanesh R, Khameneh S, Doostdar Y, Khakzad MR. Potential immunomodulation effect of the extract of Nigella sativa on ovalbumin sensitized guinea pigs. Journal of Zhejiang University Science B, 2011;12(3):201-209. https://doi.org/10.1631/jzus.B1000163
  35. Boskabady MH, Keyhanmanesh R, Saadatloo MA. Relaxant effects of different fractions from Nigella sativa L. on guinea pig tracheal chains and its possible mechanism(s). Indian Journal of Experimental Biology, 2008;46(12):805-810.
  36. Boskabady MH, Mohsenpoor N, Takaloo L. Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomedicine, 2010;17(10):707-713 https://doi.org/10.1016/j.phymed.2010.01.002
  37. Bourgou S, Pichette A, Marzouk B, Legault J. Antioxidant, antiinflammatory, anticancer and antibacterial activities of extracts from Nigella sativa (Black Cumin) plant parts. Journal of Food Biochemistry, 2012; 36(5): 539-546. https://doi.org/10.1111/j.1745-4514.2011.00567.x
  38. Butt AS, Nisar N, Ghani N, Altaf I, Mughal TA. Isolation of thymoquinone from Nigella sativa L. and Thymus vulgaris L., and its anti-proliferative effect on HeLa cancer cell lines. Tropical Journal of Pharmaceutical Research, 2019;18(1): 37-42 https://doi.org/10.4314/tjpr.v18i1.6
  39. Butt UJ, Shah SAA, Ahmed T, Zahid S. Protective effects of Nigella sativa L. seed extract on lead induced neurotoxicity during development and early life in mouse models. Toxicology Research, 2018; 7: 32-40 https://doi.org/10.1039/C7TX00201G
  40. Canayakin D, Bayir Y, Baygutalp NK, Karaoglan ES, Atmaca HT, Ozgeris FBK, Keles MS, Halici Z. Paracetamol-induced nephrotoxicity and oxidative stress in rats: the protective role of Nigella sativa. Pharmaceutical Biology, 2016;54(10):2082-91 https://doi.org/10.3109/13880209.2016.1145701
  41. 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 Complementary and Alternative Medicine, 2011;11:29. https://doi.org/10.1186/1472-6882-11-29
  42. Chehl N, Chipitsyna G, Gong Q, Yeo CJ, Arafat HA. Antiinflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells. HPB (Oxford) 2009;11(5):373-381. https://doi.org/10.1111/j.1477-2574.2009.00059.x
  43. Duncker SC, Philippe D, Martin-Paschoud C, Moser M, Mercenier A, Nutten S. Nigella sativa (Black Cumin) seed extract alleviates symptoms of allergic diarrhea in mice, involving opioid receptors. PLoS One. 2012;7(6):e39841. https://doi.org/10.1371/journal.pone.0039841
  44. Dymock W, Warden C.J.H, Hooper D. Pharmacographia Indica. Srishti Book Distributors, pp.28, 2005
  45. 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 and Clinical Pharmacology and Toxicology, 2008;103:574-80 https://doi.org/10.1111/j.1742-7843.2008.00313.x
  46. El Mezayen R, El Gazzar M, Nicolls MR, Marecki JC, Dreskin SC, Nomiyama H. Effect of thymoquinone on cyclooxygenase expression and prostaglandin production in a mouse model of allergic airway inflammation. Immunology Letter, 2006;106(1):72-81. https://doi.org/10.1016/j.imlet.2006.04.012
  47. El Shenawy NS, Soliman MF, Reyad SI. The effect of antioxidant properties of aqueous garlic extract and Nigella sativa as anti schistosomiasis agents in mice. Revista do Instituto de Medicina Tropical de Sao Paulo, 2008; 50(1): 29-36. https://doi.org/10.1590/S0036-46652008000100007
  48. El-Abhar HS, Abdallah DM, Saleh S. Gastroprotective activity of Nigella sativa oil and its constituent, thymoquinone, against gastric mucosal injury induced by ischaemia/reperfusion in rats. Journal of Ethnopharmacology, 2003;84(2-3):251-258. https://doi.org/10.1016/S0378-8741(02)00324-0
  49. El-Rabey HA, Al-Seeni MN, Bakhashwain AS. The Antidiabetic Activity of Nigella sativa and Propolis on Streptozotocin-Induced Diabetes and Diabetic Nephropathy in Male Rats. Evidence-Based Complementary and Alternative Medicine, 2017
  50. Ezz HS, Khadrawy YA, Noor NA. The neuroprotective effect of curcumin and Nigella sativa oil against oxidative stress in the pilocarpine model of epilepsy: a comparison with valproate. Neurochemical Research, 2011;36(11):2195-2204. https://doi.org/10.1007/s11064-011-0544-9
  51. Fanoudi S, Alavi MS, Hosseini M, Sadeghnia HR. Nigella sativa and thymoquinone attenuate oxidative stress and cognitive impairment following cerebral hypoperfusion in rats. Metabolic Brain Disease, 2019
  52. Fathy M, Nikaido T. In vivo attenuation of angiogenesis in hepatocellular carcinoma by Nigella sativa. Turkish Journal of Medical Sciences, 2018;48:178-186 https://doi.org/10.3906/sag-1701-86
  53. Forouzanfar F, Bazzaz BSF, Hosseinzadeh H. Black cumin (Nigella sativa) and its constituent (thymoquinone): a review on antimicrobial effects. Iranian Journal of Basic Medical Sciences, 2014;17(12)
  54. Gendy E, Hessien M, Abdel Salamm I, Moradm MEL, Magrabym K, Ibrahimm HA, et al. Evaluation of the possible antioxidant effects of Soybean and Nigella sativa during experimental hepatocarcinogenesis by nitrosamine precursors. Turkish Journal of Biochemistry, 2007;32(1):5-11.
  55. Ghani MN. Khazainul -advia. Aijaz Publication House, YNM; 3: 389-390
  56. Ghonime M, Eldomany R, Abdelaziz A, Soliman H. Evaluation of immunomodulatory effect of three herbal plants growing in Egypt. Immunopharmacology and Immunotoxicology, 2011;33(1):141-145. https://doi.org/10.3109/08923973.2010.487490
  57. Gilhotra N, Dhingra D. Thymoquinone produced antianxietylike effects in mice through modulation of GABA and NO levels. Pharmacological Reports. 2011;63(3):660-669. https://doi.org/10.1016/S1734-1140(11)70577-1
  58. Gokce A, Oktar S, Koc A, Yonden Z. Protective effects of thymoquinone against methotrexate-induced testicular injury. Human and Experimental Toxicology, 2011;30(8):897-903. https://doi.org/10.1177/0960327110382564
  59. Hadjzadeh MA, Keshavarzi Z, Yazdi TSA, Ghasem SM, Rajaei Z, Khajavi Rad A. Effect of alcoholic extract of Nigella sativa on cisplatin-induced toxicity in rat. Iranian Journal of Kidney Diseases, 2012;6(2):99-104.
  60. Hakeem AH. Bustanul Muffradat. pp. 258, YNM
  61. Halamova K, Kokoska L, Flesar J, Sklenickova O, Svobodova B, Marsik P. In vitro antifungal effect of black cumin seed quinones against dairy spoilage yeasts effect of black cumin seed quinones against dairy spoilage yeasts at different acidity levels. Journal of Food protection, 2010;73(12):2291-2295 https://doi.org/10.4315/0362-028X-73.12.2291
  62. Halawani E. Antibacterial Activity of Thymoquinone and Thymohydroquinone of Nigella sativa L. and Their Interaction with Some Antibiotics. Advances in Biological Research, 2009;3(5-6):148-152
  63. Hannan A, Saleem S, Chaudhary S, Barka M, Arshad MU. Antibacterial activity of Nigella sativa against clinical isolates of methicillin resistant Staphylococcus aureus. Journal of Ayub Medical College Abbottabad, 2008;20(3):72-74.
  64. 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 post initiation carcinogenesis. Oxidative Medicine and Cellular Longevity, 2012; 854065.
  65. Hossein BM, Nasim V, Sediqa A. The protective effect of Nigella sativa on lung injury of sulfur mustard-exposed Guinea pigs. Experimental Lung Research, 2008;34(4):183-194. https://doi.org/10.1080/01902140801935082
  66. Hosseinia M, Ghasemia S, Hadjzadehb MR, Ghorbanic A, Aghilib S, Aghaeic A, Soukhtanlood M, Beheshtie F. Administration of Nigella sativa during neonatal and juvenile growth period improved liver function of propylthiouracilinduced hypothyroid rats. The Journal of Maternal-Fetal & Neonatal Medicine, pp.1476-4954, 2018
  67. Hosseinian S, Bideskan AE, Shafei1 MN, Sadeghnia HR, Soukhtanloo M, Shahraki S, Noshahr ZS, Rad AK. Nigella sativa extract is a potent therapeutic agent for renal inflammation, apoptosis, and oxidative stress in a rat model of unilateral ureteral obstruction. Phytotherapy Research, pp.1-9, 2018
  68. Hosseinzadeh H, Bazzaz BSF, Haghi MM. Antibacterial Activity of Total Extracts and Essential oil of Nigella sativa L. Seeds in Mice. Pharmacolgyonline, 2007;2:429-435
  69. 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(9):621-627. https://doi.org/10.1016/j.phymed.2006.12.005
  70. Ikhsan M, Hiedayati N, Maeyama K, Nurwidya F. Nigella sativa as an anti-inflammatory agent in asthma. BMC Research Notes, 2018;11:744 https://doi.org/10.1186/s13104-018-3858-8
  71. Kabirruddin H. Makhaznul Muffradat. pp. 460-461, YNM
  72. Kamal SM, Lsharkawy RTE, Abdelmoneim RA. Effect of Nigella sativa on the integrity of parotid salivary gland of albino rats and its activity for insulin and glucagon. Journal of American Science, 2012;8(12):1168-1172.
  73. Kanter M, Akpolat M, Aktas C. 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, 2009; 40(5-6):379-385. https://doi.org/10.1007/s10735-009-9251-0
  74. Kanter M. Effects of Nigella sativa seed extract on ameliorating lung tissue damage in rats after experimental pulmonary aspirations. Acta Histochemical, 2009;111(5):393-403 https://doi.org/10.1016/j.acthis.2008.10.008
  75. Kapoor S. Emerging clinical and therapeutic applications of Nigella sativa in gastroenterology. World Journal of Gastroenterology, 2009;7:2170-217153. https://doi.org/10.3748/wjg.15.2170
  76. Kaur G, Invally M, Khan MK, Jadhav P. A nutraceutical combination of Cinnamomum cassia & Nigella sativa for Type 1 diabetes mellitus. Journal of Ayurveda and Integrative Medicine, 2018; 9: 27-37 https://doi.org/10.1016/j.jaim.2017.02.005
  77. Keshri G, Singh MM, Lakshmi V, Kamboj VP. Post-coital contraceptive efficacy of the seeds of Nigella sativa in rats. Indian Journal of Physiology and Pharmacology. 1995;39(1):59-62.
  78. Khader M, Bresgen N, Eckl PM. In vitro toxicological properties of thymoquinone. Food and Chemical Toxicology, 2009;47(1):129-133. https://doi.org/10.1016/j.fct.2008.10.019
  79. Khaled AAS. Gastroprotective effects of Nigella sativa oil on the formation of stress gastritis in hypothyroidal rats. International Journal of Physiology, Pathophysiology and Pharmacology, 2009;1:143-149.
  80. Khan MA. Muheete- Azam. CCRUM, 2014;3:382-385
  81. Khan MAU, Ashfaq MK, Zuberi HS, Mahmood MS, Gilani AH. The In Vivo Antifungal Activity of the Aqueous Extract from Nigella sativa Seeds. Phytotherapy Research, 2003;17:183-186 https://doi.org/10.1002/ptr.1146
  82. Khan N, Sultana S. Inhibition of two stage renal carcinogenesis, oxidative damage and hyperproliferative response by Nigella sativa. European journal of Cancer Prevention, 2005;14(2):159-168. https://doi.org/10.1097/00008469-200504000-00012
  83. Khosravi AR, Minooeianhaghighi MH, Shokri H, Emami SA, Alavi SM, Asili J. The potential inhibitory effect of cuminum cyminum, ziziphorac linopodioides and Nigella sativa essential oils on the growth of aspergillus fumigatus and aspergillus flavus. Brazilian Journal of Microbiology, 2011;42: 216-224 https://doi.org/10.1590/S1517-83822011000100027
  84. Kirtikar KR, Basu BD. Indian Medicinal Plant. International Book Distributor, 1987;1(2):11-12
  85. Kumbhakara DV, Dattaa AK, Dasa D, Ghosha B, Pramanika A, Gupta S. Assessment of oxidative stress, antioxidant enzyme activity and cellular apoptosis in a plant based system (Nigella sativa L.; black cumin) induced by copper and cadmium sulphide nanomaterials. Environmental Nanotechnology, Monitoring & Management, 2019;11 https://doi.org/10.1016/j.enmm.2017.04.001
  86. Lei X, Liu M, Yang Z, Ji M, Guo X, Dong W. Thymoquinone Prevents and ameliorates dextran sulfate sodium-induced colitis in mice. Digestive Disease and Science, 2012;57(9):2296-2303. https://doi.org/10.1007/s10620-012-2156-x
  87. Lei X, Lv X, Liu M, Yang Z, Ji M, Guo X. Thymoquinone inhibits growth and augments 5-fluorouracil-induced apoptosis in gastric cancer cells both in vitro and in vivo. Biochemical and Biophysical Research Communication, 2012; 417(2):864-868 https://doi.org/10.1016/j.bbrc.2011.12.063
  88. LorestaniHZ, Ahmadabadi AN, Balak F, Hasanzadeh G, Sabzevari O. Protective role of thymoquinone against paraquatinduced hepatotoxicity in mice. Pesticide Biochemistry and Physiology, 2018;148:16-21 https://doi.org/10.1016/j.pestbp.2018.03.006
  89. Magdy MA, Hanan el-A, Nabila el-M. Thymoquinone: Novel gastroprotective mechanisms. European Journal of Pharmacology, 2012;697(1-3):126-131. https://doi.org/10.1016/j.ejphar.2012.09.042
  90. Mahmoud SS, Torchilin VP. Hormetic/cytotoxic effects of Nigella sativa seed alcoholic and aqueous extracts on MCF-7 breast cancer cells alone or in combination with doxorubicin. Cell Biochemistry and Biophysics, 2012; 25(7):1392-1398
  91. Mahmoudvand H, Sepahvand A, Jahanbakhsh S, Ezatpour B, Mousavi SAA. Evaluation of antifungal activities of the essential oil and various extracts of Nigella sativa and its main component, thymoquinone against pathogenic dermatophyte strains. Journal de MycologieMedicale, 2014; 482: 7
  92. Majdalawieh AF, Hmaidan R, Carr RI. Nigella sativa modulates splenocyte proliferation, Th1/T2 cytokine profile, macrophage function and NK anti-tumor activity. Journal of Ethnopharmacology, 2010; 131(2):268-275. https://doi.org/10.1016/j.jep.2010.06.030
  93. 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 Chemistry, 2009; 116(1): 306-312. https://doi.org/10.1016/j.foodchem.2009.02.051
  94. Mechraoui O, Ladjel S, Nedjimi MS, Belfar ML, Moussaoui Y. Determination of polyphenols content, antioxidant and antibacterial activity of Nigella sativa L. seed phenolic extracts. Scientific study & research-Chemistry & chemical engineering, biotechnology, food industry, 2018;19(4): 411 - 421
  95. Merfort I, Wray V, Barakat HH, Hussein SAM, Nawwar M, Willuhn G. Flavonol triglycosides from seeds of Nigella sativa. Phytochemistry, 1997;46(2):359-363 https://doi.org/10.1016/S0031-9422(97)00296-3
  96. Mohamed A, Waris HM, Ramadan H, Quereshi M, Kalra J. Amelioration of chronic relapsing experimental autoimmune encephalomyelitis (cr-eae) using thymoquinone-biomed 2009. Biomedical Science Instrumentation, 2009; 45:274-279.
  97. Mohamed AM, Metwally NM, Mahmoud SS, Nigella sativa seeds against Schistosoma mansoni different stages. Memorias do Instituto Oswaldo Cruz, 2005; 100(2): 205-211.
  98. Morsi NM. Antimicrobial effect of crude extracts of Nigella sativa on multiple antibiotics-resistant bacteria. Acta Microbiologica Polonica, 2000; 49(1): 63-74.
  99. Mouwakeh A, Kincses A, Nove M, Mosolygo T, Farkas CM, Kisko G, Spengler G. Nigella sativa essential oil and its bioactive compounds as resistance modifiers against Staphylococcus aureus. Phytotherapy Research, 2019;3:1010-1018
  100. Mouwakeh A, Telbisz A, Spengler G, Farkas CM, Kisko G. Antibacterial and Resistance Modifying Activities of Nigella sativa Essential Oil and its Active Compounds Against Listeria monocytogenes. In vivo, 2018;32: 737-743 https://doi.org/10.21873/invivo.11302
  101. Nagi MN, Al-Shabanah OA, Hafez MM, Sayed-Ahmed MM. Thymoquinone supplementation attenuates cyclophosphamideinduced cardiotoxicity in rats. Journal of Biochemical and Molecular Toxicology, 2011;25:135-42 https://doi.org/10.1002/jbt.20369
  102. Najmi A, Haque SF, Naseeruddin M, Khan RA. Effect of Nigella sativa oil on various Clinical and biochemical parameters of metabolic syndrome. International Journal of Diabetes in Developing Countries, 2008; 16:85-87
  103. Nemmar A, Al-Salam S, Zia S, Marzouqi F, Al-Dhaheri A, Subramaniyan D, et al. et al. Contrasting actions of diesel exhaust particles on the pulmonary and cardiovascular systems and the effects of thymoquinone. British Journal of Pharmacology, 2011;164(7):1871-1882. https://doi.org/10.1111/j.1476-5381.2011.01442.x
  104. Ng WK, Yazan LS, Ismail M. Thymoquinone from Nigella sativa was more potent than cisplatin in eliminating of SiHa cells via apoptosis with down-regulation of Bcl-2 protein. Toxicology In vitro, 2011;25(7):1392-1398. https://doi.org/10.1016/j.tiv.2011.04.030
  105. Nickavara B, Mojaba F, Javidniab K, Amolia MAR. Chemical Composition of the Fixed and Volatile Oils of Nigella sativa L. from Iran. Z. Naturforsch, 2003;58c: 629-631
  106. Nikakhlagh S, Rahim F, Aryani FH, Syahpoush A, Brougerdnya MG, Saki N. Herbal treatment of allergic rhinitis: the use of Nigella sativa. American Journal of Otolaryngology, 2011;32(5):402-407. https://doi.org/10.1016/j.amjoto.2010.07.019
  107. Onsa RAH, Muna EA, Hassan SAA. Detection of Antibacterial Activity of the Black Cumin (Nigella sativa) Seed Extract against Mycoplasma mycoides subsp mycoides (Mmm). International Journal of Pathogen Research, 2019; 2(1): 1-6
  108. Paarakh MP. Nigella sativa Linn- A Comprehensive Review. Indian journal of natural product and resources, 2010;1(4):409-429
  109. Pari L, Sankaranarayanan C. Beneficial effects of thymoquinone on hepatic key enzymes in streptozotocin-nicotinamide induced diabetic rats. Life Science, 2009; 85(23-26):830-834. https://doi.org/10.1016/j.lfs.2009.10.021
  110. Peng L, Liu A, Shen Y, Xu HZ, Yang SZ, Ying XZ, et al. et al. Antitumor and anti-angiogenesis effects of thymoquinone on osteosarcoma through the NF-${\kappa}B$ pathway. Oncology Reports, 2013; 29(2):571-578. https://doi.org/10.3892/or.2012.2165
  111. Perveen T, Abdullah A, Haider S, Sonia B, Munawar AS, Haleem DJ. Long-term administration of Nigella sativa effects nociceotion and improves learning and memory in rats. Pakistan Journal of Biochemistry and Molecular Biology, 2008;41(3):141-143
  112. Perveen T, Haider S, Kanwal S, Haleem DJ. Repeated administration of Nigella sativa decreases 5-HT turnover and produces anxiolytic effects in rats. Pakistan Journal of Pharmaceutical Science, 2009;22(2):139-144.
  113. Phulwaria R, Kaushal K, Sharma AK, Mishra RC, Soni P. A review on folklore uses and therapeutic indications of Nigella sativa - a miracle herb. World Journal of Pharmaceutical Research, 2019; 8(1):1369-1379.
  114. Pichette A, Marzouk B, Legault J. Antioxidant, antiinflammatory, anticancer and antibacterial activities of extracts from Nigella sativa (black cumin) plant parts. Journal of Food Biochemistry, 2012; 36(5):539-546 https://doi.org/10.1111/j.1745-4514.2011.00567.x
  115. Randhawa MA, Gondal MA, Al-Zahrani AHJ, Rashid SG, Ali A. Synthesis, morphology and antifungal activity of nanoparticulated amphotericin-B, ketoconazole and thymoquinone against Candida albicans yeasts and Candida biofilm. J Environ Sci Health A Tox Hazard Subst Environ Eng, 2015;50:119-24 https://doi.org/10.1080/10934529.2015.975042
  116. Rani R, Dahiya S, Dhingra D, Dilbaghi N, Kim KH, Kumar S. Improvement of antihyperglycemic activity of nanothymoquinone in rat model of type-2 diabetes. Chemico-Biological Interactions, 2018; 295:119-132 https://doi.org/10.1016/j.cbi.2018.02.006
  117. Ranjbaran H, Abediankenari S, Amiri MM. Enhanced Differentiation of Wharton's Jelly-Derived Mesenchymal Stem Cells in Insulin-Producing Cells by the Extract of Nigella sativa Seeds. Iran Red Crescent Medical Journal, 2018; 20(3): 62111
  118. Raza M, Alghasham AA, Alorainy MS, El-Hadiyah TM. Potentiation of valproate-induced anticonvulsant response by Nigella sativa seed constituents: the role of GABA receptors. International Journal of Health Sciences, 2008;2(1):15-25
  119. Reddy SH, Al-Kalbani AS, Al-Rawahi AS. Studies on phytochemical screening - GC-MS characterization, antimicrobial and antioxidant assay of black cumin seeds (Nigella sativa) and senna alexandria (Cassia angustifolia) solvent extracts. International Journal of Pharmaceutical Sciences and Research, 2018;9(2):490-497
  120. Rogozhin EA, Oshchepkova YI, Odintsova TI, Khadeeva NV, Veshkurova ON, Egorov TA, Grishin EV, Salikhov SI. Novel antifungal defensins from Nigella sativa L. seeds. Plant Physiology and Biochemistry, 2011;49:131-137 https://doi.org/10.1016/j.plaphy.2010.10.008
  121. Sala AV. Indian medicinal plant. Orient Longman Ltd, 1997;4:139
  122. Salama RH. Hypoglycemic effect of lipoic acid, carnitine and Nigella sativa in diabetic rat model. International Journal of Health Science, 2011;5(2):126-134
  123. Saleem U, Ahmad B, Rehman K, Mahmood S, Alam M, Erum A. Nephro-protective effect of vitamin C and Nigella sativa oil on gentamicin associated nephrotoxicity in rabbits. Pakistan Journal of Pharmaceutical Science, 2012;25(4):727-730.
  124. Salem EM, Yar T, Bamosa AO, Al-Quorain A, Yasawy MI, Alsulaiman RM, et al. Comparative study of Nigella sativa and triple therapy in eradication of Helicobacter Pylori in patients with non-ulcer dyspepsia. Saudi Journal of Gastroenterology, 2010;16(3):207-214. https://doi.org/10.4103/1319-3767.65201
  125. Salem ML, Alenzi FQ, Attia WY. Thymoquinone, the active ingredient of Nigella sativa seeds, enhances survival and activity of antigen-specific CD8-positive T cells in vitro. British Journal of Biomedical Science, 2011; 68(3):131-137. https://doi.org/10.1080/09674845.2011.11730340
  126. Salim EI. Cancer chemopreventive potential of volatile oil from black cumin seeds, Nigella sativa L., in a rat multi-organ carcinogenesis bioassay. Oncology Letters, 2010;1(5):913-924 https://doi.org/10.3892/ol_00000162
  127. Satyavati GV, Gupta AK. Medicinal Plants of India. Indian Council of Medical Research, 1987; 2: 337-342
  128. Sayed-Ahmed MM, Nagi MN. Thymoquinone supplementation prevents the development of gentamicin-induced acute renal toxicity in rats. Clinical and Experimental Pharmacology and Physiology, 2007;34(5-6):399-405 https://doi.org/10.1111/j.1440-1681.2007.04560.x
  129. Shafi G, Hasan TN, Sayed NA. Methanolic extracts of Nigella sativa seed as potent lonogenic inhibitor of PC-3 cells. International Journal of Pharmacology, 2008;4(6):477-481. https://doi.org/10.3923/ijp.2008.477.481
  130. Shah SB, Shah SIA, Sartaj L, Zaman S, Bilal M, Salman M. Effect of Nigella sativa seeds extracts on clinically important bacterial and fungal species. MOJ Bioequivalence & Bioavailability, 2018; 5(4)
  131. Shuid AN, Mohamed N, Mohamed IN, Othman F, Suhaimi F, Mohd Ramli ES, Mohamed N, Soelaiman IM. Nigella sativa: A potential antiosteoporotic agent. Evidence- Based Complementary and Alternative Medicine, 2012; 2012:696230 https://doi.org/10.1155/2012/696230
  132. Sogut B, Celik I, Tuluce Y. The effects of diet supplemented with the black Cumin (Nigella sativa L.) upon immune potential and antioxidant marker enzymes and lipid peroxidation in broiler chicks. Journal of Animal and Veterinary Advances, 2008; 7(10): 1196-1199.
  133. Sultana S, Asif HM, Akhtar N, Iqbal A, Nazar H, Rehman R. Nigella sativa: Monograph. Journal of Pharmacognosy and Phytochemistry, 2015;4(4):103-106
  134. Tabassum H, Ahmad IZ. Evaluation of the Anticancer Activity of Sprout Extract-Loaded Nanoemulsion of N.sativa against Hepatocellular Carcinoma. Journal of Microencapsulation, 2019;35(7-8): 643-656 https://doi.org/10.1080/02652048.2019.1571641
  135. Tasar N, Sehirli O, Yiginer O, Soleymanoglu S, Yoksel M, Yegen B, et al. Protective effects of Nigella sativa against hypertension-induced oxidative stress and cardiovascular dysfunction in rats. Journal of Research in Pharmacy, 2012;16:141-9.
  136. Tayman C, Cekmez F, Kafa IM, Canpolat FE, Cetinkaya M, Tonbul A. Protective effects of Nigella sativa oil in hyperoxiainduced lung injury. Archivos de Bronconeumologica, 2012;49(1):15-21.
  137. Tayman C, Cekmez F, Kafa IM, Canpolat FE, Cetinkaya M, Uysal S. Beneficial effects of Nigella sativa oil on intestinal damage in necrotizing enterocolitis. Journal of Investigative Surgery, 2012;25(5):286-294. https://doi.org/10.3109/08941939.2011.639849
  138. Tembhurne SV, Feroz S, More BH, Sakarkar DM. A review on therapeutic potential of Nigella sativa (kalonji) seeds. Journal of Medicinal Plants Research,2014;8(3):167-177
  139. Torres MP, Ponnusamy MP, Chakraborty S, Smith LM, Das S, Arafat HA. Effects of thymoquinone in the expression of mucin 4 in pancreatic cancer cells: implications for the development of novel cancer therapies. Molecular Cancer Therapeutics, 2010;9(5):1419-1431. https://doi.org/10.1158/1535-7163.MCT-10-0075
  140. Ulu R, Dogukan A, Tuzcu M, Gencoglu H, Ulas M, Ilhan N. Regulation of renal organic anion and cation transporters by thymoquinone in cisplatin induced kidney injury. Food and Chemical Toxicology, 2012;50(5):1675-1679 https://doi.org/10.1016/j.fct.2012.02.082
  141. 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. Chemico- Biological Interaction, 2012;197(1):40-46. https://doi.org/10.1016/j.cbi.2012.03.003
  142. Ustuna R, Oguzb EK, Sekera A, Korkaya H. Thymoquinone prevents cisplatin neurotoxicity in primary DRG neurons. Neurotoxicology, 2018;69: 68-76 https://doi.org/10.1016/j.neuro.2018.09.001
  143. Uz E, Bayrak O, Uz E, Kaya A, Bayrak R, Uz B, et al. Nigella sativa oil for prevention of chronic cyclosporine nephrotoxicity: an experimental model. American Journal of Nephrology, 2008;28(3):517-522. https://doi.org/10.1159/000114004
  144. Wienkotter N, Hopner D, Schutte U, Bauer K, Begrow F, El-Dakhakhny M, et al. The effect of nigellone & thymoquinone on inhibiting trachea contraction and mucociliary clearance. Plant Medicine, 2008;74(2):105-108. https://doi.org/10.1055/s-2008-1034280
  145. Woo CC, Loo SY, Gee V, Yap CW, Sethi G, Kumar AP, et al. et al. Anticancer activity of thymoquinone in breast cancer cells: possible involvement of PPAR-${\gamma}$ pathway. Biochemical Pharmacology, 2011;82(5):464-475 https://doi.org/10.1016/j.bcp.2011.05.030
  146. Wu ZH, Chen Z, Shen Y, Huang LL, Jiang P. Anti-metastasis effect of thymoquinone on human pancreatic cancer. Yao Xue Xue Bao, 2011; 46(8):910-914.
  147. Yaman I, Balikci E. Protective effects of Nigella sativa against gentamicin-induced nephrotoxicity in rats. Experimental and Toxicologic Pathology, 2010;62(2):183-190. https://doi.org/10.1016/j.etp.2009.03.006
  148. Yildiz F, Coban S, Terzi A, Ates M, Aksoy N, Cakir H, et al. et al. Nigella sativa relieves the deleterious effects of ischemia reperfusion injury on liver. World Journal of Gastroenterology, 2008;14(33):5204-520952. https://doi.org/10.3748/wjg.14.5204
  149. Yildiz F, Coban S, Terzi A, Savas M, Bitiren M, Celik H. Protective effects of Nigella sativa against ischemia-reperfusion injury of kidneys. Renal Failure, 2010;32(1):126-131 https://doi.org/10.3109/08860220903367577
  150. Younus H. Antidiabetic Action of Thymoquinone. Molecular and Therapeutic actions of Thymoquinone. (Singapore: Springer), pp.7-17. 2018
  151. Zafeer MF, Waseem M, Chaudhary S, Parvez S. Cadmium-induced hepatotoxicity and its abrogation by thymoquinone. Journal of Biochemical and Molecular Toxicology, 2012;26(5):199-205. https://doi.org/10.1002/jbt.21402
  152. Zaoui A, Cherrah Y, Mahassini N, Alaoui K, Amarouch H, Hassar M. Acute and chronic toxicity of Nigella sativa fixed oil. Phytomedicine, 2002;9(1):69-74. https://doi.org/10.1078/0944-7113-00084