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ISSN (Online): 2210-3163

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Review Article

Nigella sativa, a Jack of All Trades Plant in Medicine: Pharmacological Aspects in Diseases Treatment and Prevention

Author(s): Morteza Akhzari, Shiva Mohammadi, Sajad Jalili, Mahdi Barazesh* and Karim Noorizadeh

Volume 13, Issue 6, 2023

Published on: 13 December, 2022

Article ID: e051022209588 Pages: 23

DOI: 10.2174/2210315513666221005093047

Price: $65

Abstract

Nigella sativa L. (Ranunculaceae) is one of the most widely used traditional therapeutic plants. It possesses important classes of bioactive compounds, among which thymoquinone, as the major bioactive component of the essential oil, has attracted noteworthy attention due to its active role in treating various disorders. N. sativa can induce a wide range of pharmacological functions, including anti-oxidative stress responses, antidiabetic, anticancer, cell apoptosis, increased membrane permeability, immunomodulatory, analgesic, antimicrobial, anti-inflammatory, spasmolytic, bronchodilatory, hepato-protective, renal protective, gastro-protective, and antioxidant properties. The seeds of N. sativa, commonly known as black seed or black cumin, show many potential pharmacological roles and are utilized in folk (herbal) medicine all over the world for the treatment and prevention of a various range of diseases and conditions, including asthma, cancers, inflammatory situations, type 2 diabetes mellitus disorders, bacterial and viral infections, and dyslipidemia. This review outlines the main pharmacological properties of N. sativa and its components due to their potential wide applications for a large variety of human diseases. The seeds constitute fixed and essential oils, proteins, alkaloids and saponin. Much of the biological function of the seeds has been demonstrated to be due to thymoquinone. Beneficial influences of the seeds application and thymoquinone might be contributed to their cytoprotective and antioxidant functions and their effect on immune response and some inflammatory mediators.

Keywords: Black Seed, Pharmacological effects, Thymoquinone, Medicinal plant, Natural products, Nigella sativa

Graphical Abstract

[1]
Goreja, W. Black seed: Nature’s Miracle Remedy; Karger Publishers, 2003.
[2]
el-Dakhakhny, M. Studies on the Egyptian Nigella sativa L. IV. Some pharmacological properties of the seeds’ active principle in comparison to its dihydro compound and its polymer. Drug Res., 1965, 15(10), 1227-1229.
[PMID: 4380349]
[3]
Burdock, G.A. Assessment of black cumin (Nigella sativa L.) as a food ingredient and putative therapeutic agent. Regul. Toxicol. Pharmacol., 2022, 128, 105088.
[http://dx.doi.org/10.1016/j.yrtph.2021.105088] [PMID: 34838871]
[4]
Al-Rowais, N.A. Herbal medicine in the treatment of diabetes mellitus. Saudi Med. J., 2002, 23(11), 1327-1331.
[PMID: 12506289]
[5]
Burits, M.; Bucar, F. Antioxidant activity of Nigella sativa essential oil. Phytother. Res., 2000, 14(5), 323-328.
[http://dx.doi.org/10.1002/1099-1573(200008)14:5<323:AID-PTR621>3.0.CO;2-Q] [PMID: 10925395]
[6]
El-Dakhakhny, M.; Barakat, M.; Abd El-Halim, M.; Aly, S.M. Effects of Nigella sativa oil on gastric secretion and ethanol induced ulcer in rats. J. Ethnopharmacol., 2000, 72(1-2), 299-304.
[http://dx.doi.org/10.1016/S0378-8741(00)00235-X] [PMID: 10967486]
[7]
Atta-ur-Rahman. Malik, S.; Cun-heng, H.; Clardy, J. Isolation and structure determination of nigellicine, a novel alkaloid from the seeds of. Tetrahedron Lett., 1985, 26(23), 2759-2762.
[http://dx.doi.org/10.1016/S0040-4039(00)94904-9]
[8]
Atta-ur-Rahman. Malik, S.; Hasan, S.S.; Choudhary, M.I.; Ni, C-Z.; Clardy, J. Nigellidine - A new indazole alkaloid from the seeds of Nigella sativa. Tetrahedron Lett., 1995, 36(12), 1993-1996.
[http://dx.doi.org/10.1016/0040-4039(95)00210-4]
[9]
Atta-ur-Rahman. Malik, S.; Zaman, K. Nigellimine: A new isoquinoline alkaloid from the seeds of Nigella sativa. J. Nat. Prod., 1992, 55(5), 676-678.
[http://dx.doi.org/10.1021/np50083a020]
[10]
Atta-ur-Rahman. Malik, S.; Ahmad, S.; Chaudhary, I.; Habib-ur-Rehman. Nigellimine N-oxide-a new isoquinoline alkaloid from the seeds of Nigella sativa. Heterocycles, 1985, 23(4), 953-955.
[http://dx.doi.org/10.3987/R-1985-04-0953]
[11]
Ghosheh, O.A.; Houdi, A.A.; Crooks, P.A. High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). J. Pharm. Biomed. Anal., 1999, 19(5), 757-762.
[http://dx.doi.org/10.1016/S0731-7085(98)00300-8] [PMID: 10698539]
[12]
Al-Jassir, M.S. Chemical composition and microflora of black cumin (Nigella sativa L.) seeds growing in Saudi Arabia. Food Chem., 1992, 45(4), 239-242.
[http://dx.doi.org/10.1016/0308-8146(92)90153-S]
[13]
Bhatia, I.S.; Bajaj, K.L. Tannins in black-plum (Syzygium cumini L.) seeds. Biochem. J., 1972, 128(1), 56P.
[http://dx.doi.org/10.1042/bj1280056Pa] [PMID: 5085637]
[14]
Chun, H.; Shin, D.H.; Hong, B.S.; Cho, W.D.; Cho, H.Y.; Yang, H.C. Biochemical properties of polysaccharides from black pepper. Biol. Pharm. Bull., 2002, 25(9), 1203-1208.
[http://dx.doi.org/10.1248/bpb.25.1203] [PMID: 12230118]
[15]
Correa, A.D.; Jokl, L.; Carlsson, R. Amino acid composition of some Amaranthus sp. grain proteins and of its fractions. Arch. Latinoam. Nutr., 1986, 36(3), 466-476.
[PMID: 3632220]
[16]
Merfort, I.; Wray, V.; Barakat, H.H.; Hussein, S.A.M.; Nawwar, M.A.M.; Willuhn, G. Flavonol triglycosides from seeds of Nigella sativa. Phytochemistry, 1997, 46(2), 359-363.
[http://dx.doi.org/10.1016/S0031-9422(97)00296-3]
[17]
Al-Saleh, I.A.; Billedo, G.; El-Doush, I.I. Levels of selenium, dl-α-tocopherol, dl-γ-tocopherol, all-trans-retinol, thymoquinone and thymol in different brands of Nigella sativa seeds. J. Food Compos. Anal., 2006, 19(2-3), 167-175.
[http://dx.doi.org/10.1016/j.jfca.2005.04.011]
[18]
Salem, M.L.; Hossain, M.S. Protective effect of black seed oil from Nigella sativa against murine cytomegalovirus infection. Int. J. Immunopharmacol., 2000, 22(9), 729-740.
[http://dx.doi.org/10.1016/S0192-0561(00)00036-9] [PMID: 10884593]
[19]
Mazaheri, Y.; Torbati, M.; Azadmard-Damirchi, S.; Savage, G.P. A comprehensive review of the physicochemical, quality and nutritional properties of Nigella sativa oil. Food Rev. Int., 2019, 35(4), 342-362.
[http://dx.doi.org/10.1080/87559129.2018.1563793]
[20]
Ahmad, A.; Mishra, R.K.; Vyawahare, A.; Kumar, A.; Rehman, M.U.; Qamar, W.; Khan, A.Q.; Khan, R. Thymoquinone (2-Isopropyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects. Saudi Pharm. J., 2019, 27(8), 1113-1126.
[http://dx.doi.org/10.1016/j.jsps.2019.09.008] [PMID: 31885471]
[21]
Randhawa, M.A.; Alghamdi, M.S.; Maulik, S.K. The effect of thymoquinone, an active component of Nigella sativa, on isoproterenol induced myocardial injury. Pak. J. Pharm. Sci., 2013, 26(6), 1215-1219.
[PMID: 24191329]
[22]
Fatima Shad, K.; Soubra, W.; Cordato, D.J. The role of thymoquinone, a major constituent of Nigella sativa, in the treatment of inflammatory and infectious diseases. Clin. Exp. Pharmacol. Physiol., 2021, 48(11), 1445-1453.
[http://dx.doi.org/10.1111/1440-1681.13553] [PMID: 34297870]
[23]
Chowdhury, F. A.; Hossain, M. K.; Mostofa, A.; Akbor, M. M.; Bin Sayeed, M. S. Therapeutic potential of thymoquinone in glioblastoma treatment: Targeting major gliomagenesis signaling pathways. BioMed Res. Int., 2018, 2018
[24]
Goyal, S.N.; Prajapati, C.P.; Gore, P.R.; Patil, C.R.; Mahajan, U.B.; Sharma, C.; Talla, S.P.; Ojha, S.K. Therapeutic potential and pharmaceutical development of thymoquinone: A multitargeted molecule of natural origin. Front. Pharmacol., 2017, 8, 656.
[http://dx.doi.org/10.3389/fphar.2017.00656] [PMID: 28983249]
[25]
Alam, M.; Hasan, G.M.; Ansari, M.M.; Sharma, R.; Yadav, D.K.; Hassan, M.I. Therapeutic implications and clinical manifestations of thymoquinone. Phytochemistry, 2022, 200, 113213.
[http://dx.doi.org/10.1016/j.phytochem.2022.113213] [PMID: 35472482]
[26]
Avula, B.; Wang, Y.H.; Ali, Z.; Khan, I.A. Quantitative determination of chemical constituents from seeds of Nigella sativa L. using HPLC-UV and identification by LC-ESI-TOF. J. AOAC Int., 2010, 93(6), 1778-1787.
[http://dx.doi.org/10.1093/jaoac/93.6.1778] [PMID: 21313803]
[27]
Khan, A.; Chen, H-C.; Tania, M.; Zhang, D-Z. Anticancer activities of Nigella sativa (black cumin). Afr. J. Tradit. Complement. Altern. Med., 2011, 8(5S)(Suppl.), 226-232.
[http://dx.doi.org/10.4314/ajtcam.v8i5S.10] [PMID: 22754079]
[28]
Xue, W.; Batushansky, A.; Toubiana, D.; Botnick, I.; Szymanski, J.; Khozin-Goldberg, I.; Nikoloski, Z.; Lewinsohn, E.; Fait, A. The investment in scent: Time-resolved metabolic processes in developing volatile-producing Nigella sativa L. seeds. PLoS One, 2013, 8(9), e73061.
[http://dx.doi.org/10.1371/journal.pone.0073061] [PMID: 24019893]
[29]
Hannan, M.A.; Zahan, M.S.; Sarker, P.P.; Moni, A.; Ha, H.; Uddin, M.J. Protective effects of black cumin (Nigella sativa) and its bioactive constituent, thymoquinone against kidney injury: An aspect on pharmacological insights. Int. J. Mol. Sci., 2021, 22(16), 9078.
[http://dx.doi.org/10.3390/ijms22169078] [PMID: 34445781]
[30]
Farag, M.A.; El-Kersh, D.M.; Rasheed, D.M.; Heiss, A.G. Volatiles distribution in Nigella species (black cumin seeds) and in response to roasting as analyzed via solid-phase microextraction (SPME) coupled to chemometrics. Ind. Crops Prod., 2017, 108, 564-571.
[http://dx.doi.org/10.1016/j.indcrop.2017.07.011]
[31]
el Daly, E.S. Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats. J. Pharm. Belg., 1998, 53(2), 87-93.
[PMID: 9609969]
[32]
Yun, Q.; Liu, Q.; He, C.; Ma, X.; Gao, X.; Talbi, A.; Zhou, J. UPLC-Q-TOF/MS characterization, HPLC fingerprint analysis and species differentiation for quality control of Nigella glandulifera Freyn et Sint seeds and Nigella sativa L. seeds. Anal. Methods, 2014, 6(13), 4845-4852.
[http://dx.doi.org/10.1039/c4ay00775a]
[33]
Maulidiani, M.; Sheikh, B.Y.; Mediani, A.; Wei, L.S.; Ismail, I.S.; Abas, F.; Lajis, N.H. Differentiation of Nigella sativa seeds from four different origins and their bioactivity correlations based on NMR-metabolomics approach. Phytochem. Lett., 2015, 13, 308-318.
[http://dx.doi.org/10.1016/j.phytol.2015.07.012]
[34]
Mudie, K.; Seifu, D.; Challa, F.; Abebe, A.; Debella, A.; Gebregzabher, A. Hepatoprotective activity of aqueous seed extract of Nigella sativa against highly active antiretroviral therapy induced hepatotoxicity in rats. Pharmacol Online, 2014, 3, 11-21.
[35]
Hagel, J.M.; Mandal, R.; Han, B.; Han, J.; Dinsmore, D.R.; Borchers, C.H.; Wishart, D.S.; Facchini, P.J. Metabolome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants. BMC Plant Biol., 2015, 15(1), 220.
[http://dx.doi.org/10.1186/s12870-015-0594-2] [PMID: 26369413]
[36]
Asif, S.; Malik, L. Protective effects of Nigella sativa on acetylsalicylic acid-induced nephrotoxicity in albino rats. J. Coll. Physicians Surg. Pak., 2017, 27(9), 536-539.
[PMID: 29017666]
[37]
Jahromy, M. H.; Jalili, M.; Mohajer, A. J.; Poor, F. K.; Dara, S. M. Effects of Nigella sativa seed extract on perphenzine-induced muscle rigidity in male mice. World J. Neurosci., 2014, 2014
[38]
Farag, M.A.; El Sayed, A.M.; El Banna, A.; Ruehmann, S. Metabolomics reveals distinct methylation reaction in MeJA elicited Nigella sativa callus via UPLC–MS and chemometrics. Plant Cell Tissue Organ Cult., 2015, 122(2), 453-463.
[http://dx.doi.org/10.1007/s11240-015-0782-7]
[39]
Akhondian, J.; Parsa, S.; Rakhshande, H. The effect of Nigella sativa L. (black cumin seed) on intractable pediatric seizures. Med. Sci. Monit., 2007, 13(12), 559.
[40]
Kökten, N. Eğilmez, O.K.; Erinç, M.; Doğan Ekici, A.I.; Şerifler, S.; Yeşilada, E.; Kalcıoğlu, M.T. The protective effect of Nigella sativa oil against experimentally induced cisplatin ototoxicity: An animal study. J. Int. Adv. Otol., 2020, 16(3), 346-352.
[http://dx.doi.org/10.5152/iao.2020.7761] [PMID: 33136014]
[41]
Kıralan, M. Changes in volatile compounds of black cumin (Nigella sativa L.) seed oil during thermal oxidation. Int. J. Food Prop., 2014, 17(7), 1482-1489.
[http://dx.doi.org/10.1080/10942912.2012.723231]
[42]
Elsherbiny, N.M.; Maysarah, N.M.; El-Sherbiny, M.; Al-Gayyar, M.M. Renal protective effects of thymoquinone against sodium nitrite-induced chronic toxicity in rats: Impact on inflammation and apoptosis. Life Sci., 2017, 180, 1-8.
[http://dx.doi.org/10.1016/j.lfs.2017.05.005] [PMID: 28495515]
[43]
Sedaghat, R.; Roghani, M.; Khalili, M. Neuroprotective effect of thymoquinone, the Nigella sativa bioactive compound, in 6-hydroxydopamine-induced hemi-parkinsonian rat model. Iran. J. Pharm. Res., 2014, 13(1), 227-234.
[PMID: 24734075]
[44]
Kanter, M. Nigella sativa and derived thymoquinone prevents hippocampal neurodegeneration after chronic toluene exposure in rats. Neurochem. Res., 2008, 33(3), 579-588.
[http://dx.doi.org/10.1007/s11064-007-9481-z] [PMID: 17929168]
[45]
Ramadan, M.F. Black Cumin (Nigella sativa) Seeds: Chemistry, Technology, Functionality, and Applications; Springer Nature: London, 2020.
[46]
Ahmad, A.; Husain, A.; Mujeeb, M.; Khan, S.A.; Najmi, A.K.; Siddique, N.A.; Damanhouri, Z.A.; Anwar, F. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac. J. Trop. Biomed., 2013, 3(5), 337-352.
[http://dx.doi.org/10.1016/S2221-1691(13)60075-1] [PMID: 23646296]
[47]
Houghton, P.; Zarka, R.; de las Heras, B.; Hoult, J. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Med., 1995, 61(1), 33-36.
[http://dx.doi.org/10.1055/s-2006-957994] [PMID: 7700988]
[48]
Khan, N.; Sultana, S. Inhibition of two stage renal carcinogenesis, oxidative damage and hyperproliferative response by Nigella sativa. Eur. J. Cancer Prev., 2005, 14(2), 159-168.
[http://dx.doi.org/10.1097/00008469-200504000-00012] [PMID: 15785320]
[49]
Thabrew, M.I.; Mitry, R.R.; Morsy, M.A.; Hughes, R.D. Cytotoxic effects of a decoction of Nigella sativa, Hemidesmus indicus and Smilax glabra on human hepatoma HepG2 cells. Life Sci., 2005, 77(12), 1319-1330.
[http://dx.doi.org/10.1016/j.lfs.2005.01.022] [PMID: 15916774]
[50]
Ahmad, S.; Beg, Z.H. Hypolipidemic and antioxidant activities of thymoquinone and limonene in atherogenic suspension fed rats. Food Chem., 2013, 138(2-3), 1116-1124.
[http://dx.doi.org/10.1016/j.foodchem.2012.11.109] [PMID: 23411222]
[51]
Aboul-Ela, E.I. Cytogenetic studies on Nigella sativa seeds extract and thymoquinone on mouse cells infected with schistosomiasis using karyotyping. Mutat. Res. Genet. Toxicol. Environ. Mutagen., 2002, 516(1-2), 11-17.
[http://dx.doi.org/10.1016/S1383-5718(01)00333-3] [PMID: 11943605]
[52]
Singh, G.; Marimuthu, P.; de Heluani, C.S.; Catalan, C. Chemical constituents and antimicrobial and antioxidant potentials of essential oil and acetone extract of Nigella sativa seeds. J. Sci. Food Agric., 2005, 85(13), 2297-2306.
[http://dx.doi.org/10.1002/jsfa.2255]
[53]
Ramadan, M.F.; Mörsel, J.T. Oxidative stability of black cumin (Nigella sativa L.), coriander (Coriandrum sativum L.) and niger (Guizotia abyssinica Cass.) crude seed oils upon stripping. Eur. J. Lipid Sci. Technol., 2004, 106(1), 35-43.
[http://dx.doi.org/10.1002/ejlt.200300895]
[54]
Yanishlieva, N.V.; Marinova, E.M. Stabilisation of edible oils with natural antioxidants. Eur. J. Lipid Sci. Technol., 2001, 103(11), 752-767.
[http://dx.doi.org/10.1002/1438-9312(200111)103:11<752:AID-EJLT752>3.0.CO;2-0]
[55]
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(4), 217-224.
[http://dx.doi.org/10.1007/s00204-005-0037-1] [PMID: 16240107]
[56]
Çetin, M. Yurtseven, S.; Şengül, T.; Sögüt, B. Effect of black seed extract (Nigella sativa) on growth performance, blood parameters, oxidative stress and DNA damage of partridges. J. Appl. Anim. Res., 2008, 34(2), 121-125.
[http://dx.doi.org/10.1080/09712119.2008.9706955]
[57]
Abdel-Wahhab, M.A.; Aly, S.E. Antioxidant property of Nigella sativa (black cumin) and Syzygium aromaticum (clove) in rats during aflatoxicosis. J. Appl. Toxicol., 2005, 25(3), 218-223.
[http://dx.doi.org/10.1002/jat.1057] [PMID: 15856529]
[58]
Alyoussef, A.; Al-Gayyar, M.M.H. Thymoquinone ameliorated elevated inflammatory cytokines in testicular tissue and sex hormones imbalance induced by oral chronic toxicity with sodium nitrite. Cytokine, 2016, 83, 64-74.
[http://dx.doi.org/10.1016/j.cyto.2016.03.018] [PMID: 27038016]
[59]
Badary, O.A.; Abdel-Naim, A.B.; Abdel-Wahab, M.H.; Hamada, F.M.A. The influence of thymoquinone on doxorubicin-induced hyperlipidemic nephropathy in rats. Toxicology, 2000, 143(3), 219-226.
[http://dx.doi.org/10.1016/S0300-483X(99)00179-1] [PMID: 10755708]
[60]
Mansour, M.A.; Nagi, M.N.; El-Khatib, A.S.; Al-Bekairi, A.M. Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and DT-diaphorase in different tissues of mice: A possible mechanism of action. Cell Biochem. Funct., 2002, 20(2), 143-151.
[http://dx.doi.org/10.1002/cbf.968] [PMID: 11979510]
[61]
Mostafa, R.M.; Moustafa, Y.M.; Mirghani, Z.; AlKusayer, G.M.; Moustafa, K.M. Antioxidant effect of garlic (Allium sativum) and black seeds (Nigella sativa) in healthy postmenopausal women. SAGE Open Med., 2013, 1.
[http://dx.doi.org/10.1177/2050312113517501] [PMID: 26770698]
[62]
Sultan, M.T.; Butt, M.S.; Karim, R.; Ahmed, W.; Kaka, U.; Ahmad, S.; Dewanjee, S.; Jaafar, H.Z.E.; Zia-Ul-Haq, M. Nigella sativa fixed and essential oil modulates glutathione redox enzymes in potassium bromate induced oxidative stress. BMC Complement. Altern. Med., 2015, 15(1), 330.
[http://dx.doi.org/10.1186/s12906-015-0853-7] [PMID: 26385559]
[63]
El-Saleh, S.C.; Al-Sagair, O.A.; Al-Khalaf, M.I. Thymoquinone and Nigella sativa oil protection against methionine-induced hyperhomocysteinemia in rats. Int. J. Cardiol., 2004, 93(1), 19-23.
[http://dx.doi.org/10.1016/S0167-5273(03)00108-6] [PMID: 14729430]
[64]
Hosseinzadeh, H.; Parvardeh, S.; Asl, M.N.; Sadeghnia, H.R.; 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.
[http://dx.doi.org/10.1016/j.phymed.2006.12.005] [PMID: 17291733]
[65]
Cemek, M.; Enginar, H.; Karaca, T.; Ünak, P. In vivo radioprotective effects of Nigella sativa L oil and reduced glutathione against irradiation-induced oxidative injury and number of peripheral blood lymphocytes in rats. Photochem. Photobiol., 2006, 82(6), 1691-1696.
[http://dx.doi.org/10.1111/j.1751-1097.2006.tb09832.x] [PMID: 17387769]
[66]
El-Abhar, H.S.; Abdallah, D.M.; Saleh, S. Gastroprotective activity of Nigella sativa oil and its constituent, thymoquinone, against gastric mucosal injury induced by ischaemia/reperfusion in rats. J. Ethnopharmacol., 2003, 84(2-3), 251-258.
[http://dx.doi.org/10.1016/S0378-8741(02)00324-0] [PMID: 12648823]
[67]
Sallal, A.; Alkofahi, A. Inhibition of the haemolytic activities of snake and scorpion venoms in vitro with plant extracts Biomed.Lett., 1996, 211-215.
[68]
Bimonte, S.; Albino, V.; Barbieri, A.; Tamma, M.L.; Nasto, A.; Palaia, R.; Molino, C.; Bianco, P.; Vitale, A.; Schiano, R.; Giudice, A.; Cascella, M. Dissecting the roles of thymoquinone on the prevention and the treatment of hepatocellular carcinoma: An overview on the current state of knowledge. Infect. Agent. Cancer, 2019, 14(1), 10.
[http://dx.doi.org/10.1186/s13027-019-0226-9] [PMID: 31015860]
[69]
Salim, E.I.; Fukushima, S. Chemopreventive potential of volatile oil from black cumin (Nigella sativa L.) seeds against rat colon carcinogenesis. Nutr. Cancer, 2003, 45(2), 195-202.
[http://dx.doi.org/10.1207/S15327914NC4502_09] [PMID: 12881014]
[70]
Farah, I.O.; Begum, R.A. Effect of Nigella sativa and oxidative stress on the survival pattern of MCF-7 breast cancer cells. Biomed. Sci. Instrum., 2003, 39, 359-364.
[PMID: 12724920]
[71]
Awad, E.M. In vitro decreases of the fibrinolytic potential of cultured human fibrosarcoma cell line, HT1080, by Nigella sativa oil. Phytomedicine, 2005, 12(1-2), 100-107.
[http://dx.doi.org/10.1016/j.phymed.2003.09.003] [PMID: 15693715]
[72]
Shafiq, H.; Ahmad, A.; Masud, T.; Kaleem, M. Cardio-protective and anti-cancer therapeutic potential of Nigella sativa. Iran. J. Basic Med. Sci., 2014, 17(12), 967-979.
[PMID: 25859300]
[73]
Shoieb, A.; Elgayyar, M.; Dudrick, P.; Bell, J.; Tithof, P. In vitro inhibition of growth and induction of apoptosis in cancer cell lines by thymoquinone. Int. J. Oncol., 2003, 22(1), 107-113.
[http://dx.doi.org/10.3892/ijo.22.1.107] [PMID: 12469192]
[74]
Gali-Muhtasib, H.; Roessner, A.; Schneider-Stock, R. Thymoquinone: A promising anti-cancer drug from natural sources. Int. J. Biochem. Cell Biol., 2006, 38(8), 1249-1253.
[http://dx.doi.org/10.1016/j.biocel.2005.10.009] [PMID: 16314136]
[75]
Gali-Muhtasib, H.; Diab-Assaf, M.; Boltze, C.; Al-Hmaira, J.; Hartig, R.; Roessner, A.; Schneider-Stock, R. Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism. Int. J. Oncol., 2004, 25(4), 857-866.
[PMID: 15375533]
[76]
Swamy, S.M.K.; Tan, B.K.H. Cytotoxic and immunopotentiating effects of ethanolic extract of Nigella sativa L. seeds. J. Ethnopharmacol., 2000, 70(1), 1-7.
[http://dx.doi.org/10.1016/S0378-8741(98)00241-4] [PMID: 10720783]
[77]
Mostofa, A.G.M.; Hossain, M.K.; Basak, D.; Bin Sayeed, M.S. Thymoquinone as a potential adjuvant therapy for cancer treatment: Evidence from preclinical studies. Front. Pharmacol., 2017, 8, 295.
[http://dx.doi.org/10.3389/fphar.2017.00295] [PMID: 28659794]
[78]
Salomi, N.J.; Nair, S.C.; Jayawardhanan, K.K.; Varghese, C.D.; Panikkar, K.R. Antitumour principles from Nigella sativa seeds. Cancer Lett., 1992, 63(1), 41-46.
[http://dx.doi.org/10.1016/0304-3835(92)90087-C] [PMID: 1555206]
[79]
Worthen, D.R.; Ghosheh, O.A.; Crooks, P.A. The in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa L. Anticancer Res., 1998, 18(3A), 1527-1532.
[PMID: 9673365]
[80]
Ait Mbarek, L.; Ait Mouse, H.; Elabbadi, N.; Bensalah, M.; Gamouh, A.; Aboufatima, R.; Benharref, A.; Chait, A.; Kamal, M.; Dalal, A.; Zyad, A. Anti-tumor properties of blackseed (Nigella sativa L.) extracts. Braz. J. Med. Biol. Res., 2007, 40(6), 839-847.
[http://dx.doi.org/10.1590/S0100-879X2006005000108] [PMID: 17581684]
[81]
Salomi, M.; Nair, S. C.; Panikkar, K. Inhibitory effects of Nigella sativa and saffron (Crocus sativus) on chemical carcinogenesis in mice. 1991, 16(1), 67-72.
[82]
Fathy, M.; Nikaido, T. In vivo attenuation of angiogenesis in hepatocellular carcinoma by Nigella sativa. Turk. J. Med. Sci., 2018, 48(1), 178-186.
[http://dx.doi.org/10.3906/sag-1701-86] [PMID: 29479981]
[83]
Zhang, L.; Bai, Y.; Yang, Y. Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-κB. Oncol. Lett., 2016, 12(4), 2840-2845.
[http://dx.doi.org/10.3892/ol.2016.4971] [PMID: 27698868]
[84]
Muthu Kumara, S.S.; Huat, B.T.K. Extraction, isolation and characterisation of antitumor principle, α-hederin, from the seeds of Nigella sativa. Planta Med., 2001, 67(1), 29-32.
[http://dx.doi.org/10.1055/s-2001-10628] [PMID: 11270717]
[85]
Zhu, W.Q.; Wang, J.; Guo, X.F.; Liu, Z.; Dong, W.G. Thymoquinone inhibits proliferation in gastric cancer via the STAT3 pathway in vivo and in vitro. World J. Gastroenterol., 2016, 22(16), 4149-4159.
[http://dx.doi.org/10.3748/wjg.v22.i16.4149] [PMID: 27122665]
[86]
Al-Shabanah, O.A.; Badary, O.A.; Nagi, M.N.; al-Gharably, N.M.; al-Rikabi, A.C.; al-Bekairi, A.M. Thymoquinone protects against doxorubicin-induced cardiotoxicity without compromising its antitumor activity. J. Exp. Clin. Cancer Res., 1998, 17(2), 193-198.
[PMID: 9700580]
[87]
Mabrouk, G.M.; Moselhy, S.S.; Zohny, S.F.; Ali, E.M.; Helal, T.E.; Amin, A.A.; Khalifa, A.A. Inhibition of methylnitrosourea (MNU) induced oxidative stress and carcinogenesis by orally administered bee honey and Nigella grains in Sprague Dawely rats. J. Exp. Clin. Cancer Res., 2002, 21(3), 341-346.
[PMID: 12385575]
[88]
Abo-Atya, D.M.; El-Mallah, M.F.; El-Seedi, H.R.; Farag, M.A. Novel Prospective of N. sativa Essential Oil Analysis, Culinary and Medicinal Uses. Black cumin (Nigella sativa) seeds: Chemistry, Technology, Functionality, and Applications; Springer, 2021, pp. 97-129.
[http://dx.doi.org/10.1007/978-3-030-48798-0_9]
[89]
S, V.T.; S, F.; B, H.M.; D, M.S. A review on therapeutic potential of Nigella sativa (kalonji) seeds. J. Med. Plants Res., 2014, 8(3), 167-177.
[http://dx.doi.org/10.5897/JMPR10.737]
[90]
Hailat, N.; Bataineh, Z.; Lafi, S.; Raweily, E.; Aqel, M.; Al-Katib, M.; Hanash, S. Effect of Nigella sativa volatile oil on Jurkat T cell leukemia polypeptides. Int. J. Pharmacogn., 1995, 33(1), 16-20.
[91]
Khajavi Ra, A.; Shafiee, S.; Ebrahimzad, A.; Rajaei, Z.; Mohammadia, N.; Alavinezha, A.; Havakhah, S.; Hossienian, S.; Shahraki, S. Effects of aqueous-ethanolic extract of Nigella sativa seeds (black cumin) and vitamin E on cisplatin-induced nephrotoxicity in rat. Res. J. Med. Plant, 2016, 10(4), 295-302.
[http://dx.doi.org/10.3923/rjmp.2016.295.302]
[92]
Badary, O.A. Thymoquinone attenuates ifosfamide-induced Fanconi syndrome in rats and enhances its antitumor activity in mice. J. Ethnopharmacol., 1999, 67(2), 135-142.
[http://dx.doi.org/10.1016/S0378-8741(98)00242-6] [PMID: 10619376]
[93]
Badary, O.A.; Nagi, M.N.; Al-Shabanah, O.A.; Al-Sawaf, H.A.; Al-Sohaibani, M.O.; Al-Bekairi, A.M. Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and potentiates its antitumor activity. Can. J. Physiol. Pharmacol., 1997, 75(12), 1356-1361.
[http://dx.doi.org/10.1139/y97-169] [PMID: 9534946]
[94]
Badary, O.A. AI-Shabanah, O.A.; Nagi, M.N.; AI-Rikabi, A.C.; Elmazar, M.M.A. Inhibition of benzo(a)pyrene-induced forestomach carcinogenesis in mice by thymoquinone. Eur. J. Cancer Prev., 1999, 8(5), 435-440.
[http://dx.doi.org/10.1097/00008469-199910000-00009] [PMID: 10548399]
[95]
Badary, O.A.; Gamal El-Din, A.M. Inhibitory effects of thymoquinone against 20-methylcholanthrene-induced fibrosarcoma tumorigenesis. Cancer Detect. Prev., 2001, 25(4), 362-368.
[PMID: 11531013]
[96]
Majdalawieh, A.F.; Hmaidan, R.; Carr, R.I. Nigella sativa modulates splenocyte proliferation, Th1/Th2 cytokine profile, macrophage function and NK anti-tumor activity. J. Ethnopharmacol., 2010, 131(2), 268-275.
[http://dx.doi.org/10.1016/j.jep.2010.06.030] [PMID: 20600757]
[97]
Swamy, S.M.; Huat, B.T. Intracellular glutathione depletion and reactive oxygen species generation are important in α-hederin-induced apoptosis of P388 cells. Mol. Cell. Biochem., 2003, 245(1-2), 127-139.
[PMID: 12708752]
[98]
Kaleem, M.; Kirmani, D.; Asif, M.; Ahmed, Q.; Bano, B. Biochemical effects of Nigella sativa L. seeds in diabetic rats. 2006.
[99]
Altan, M.F.; Kanter, M.; Donmez, S.; Kartal, M.E.; Buyukbas, S. Combination therapy of Nigella sativa and human parathyroid hormone on bone mass, biomechanical behavior and structure in streptozotocin-induced diabetic rats. Acta Histochem., 2007, 109(4), 304-314.
[http://dx.doi.org/10.1016/j.acthis.2007.02.006] [PMID: 17395251]
[100]
Najmi, A.; Nasiruddin, M.; Khan, R.; Haque, S. Effect of Nigella sativa oil on various clinical and biochemical parameters of insulin resistance syndrome. Int. J. Diabetes Dev. Ctries., 2008, 28(1), 11-14.
[http://dx.doi.org/10.4103/0973-3930.41980] [PMID: 19902033]
[101]
Fararh, K.M.; Atoji, Y.; Shimizu, Y.; Shiina, T.; Nikami, H.; Takewaki, T. Mechanisms of the hypoglycaemic and immunopotentiating effects of Nigella sativa L. oil in streptozotocin-induced diabetic hamsters. Res. Vet. Sci., 2004, 77(2), 123-129.
[http://dx.doi.org/10.1016/j.rvsc.2004.03.002] [PMID: 15196902]
[102]
Rchid, H.; Chevassus, H.; Nmila, R.; Guiral, C.; Petit, P.; Chokaïri, M.; Sauvaire, Y. Nigella sativa seed extracts enhance glucose-induced insulin release from rat-isolated Langerhans islets. Fundam. Clin. Pharmacol., 2004, 18(5), 525-529.
[http://dx.doi.org/10.1111/j.1472-8206.2004.00275.x] [PMID: 15482373]
[103]
Maideen, N.M.P. Antidiabetic activity of Nigella sativa (black seeds) and its active constituent (thymoquinone): A review of human and experimental animal studies. Chonnam Med. J., 2021, 57(3), 169-175.
[http://dx.doi.org/10.4068/cmj.2021.57.3.169] [PMID: 34621636]
[104]
Raish, M.; Ahmad, A.; Jan, B. L.; Alkharfy, K. M.; Mohsin, K.; Ahamad, S. R.; Ansari, M. A. GC-MS-based metabolomic profiling of thymoquinone in streptozotocin-induced diabetic nephropathy in rats. Nat. Prod. Commun, 2017, 12(4), 1934578X1701200423.
[http://dx.doi.org/10.1177/1934578X1701200423]
[105]
Akhtar, M.T.; Qadir, R.; Bukhari, I.; Ashraf, R.A.; Malik, Z.; Zahoor, S.; Murtaza, M.A.; Siddique, F.; Shah, S.N.H.; Saadia, M. Antidiabetic potential of Nigella sativa L seed oil in alloxaninduced diabetic rabbits. Trop. J. Pharm. Res., 2020, 19(2), 283-289.
[http://dx.doi.org/10.4314/tjpr.v19i2.10]
[106]
Kaatabi, H.; Bamosa, A.O.; Badar, A.; Al-Elq, A.; Abou-Hozaifa, B.; Lebda, F.; Al-Khadra, A.; Al-Almaie, S. Nigella sativa improves glycemic control and ameliorates oxidative stress in patients with type 2 diabetes mellitus: Placebo controlled participant blinded clinical trial. PLoS One, 2015, 10(2), e0113486.
[http://dx.doi.org/10.1371/journal.pone.0113486] [PMID: 25706772]
[107]
Meral, I.; Yener, Z.; Kahraman, T.; Mert, N. Effect of Nigella sativa on glucose concentration, lipid peroxidation, anti-oxidant defence system and liver damage in experimentally-induced diabetic rabbits. J. Vet. Med. A Physiol. Pathol. Clin. Med., 2001, 48(10), 593-599.
[http://dx.doi.org/10.1046/j.1439-0442.2001.00393.x] [PMID: 11848252]
[108]
Hawsawi, Z.A.; Ali, B.A.; Bamosa, A.O. Effect of Nigella sativa (Black Seed) and thymoquinone on blood glucose in albino rats. Ann. Saudi Med., 2001, 21(3-4), 242-244.
[http://dx.doi.org/10.5144/0256-4947.2001.242] [PMID: 17264566]
[109]
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(1), 685-691.
[110]
Mansi, K.M.S. Effects of oral administration of water extract of Nigella sativa on serum concentrations of insulin and testosterone in alloxan-induced diabetic rats. Pak. J. Biol. Sci., 2005, 8(8), 1152-1156.
[http://dx.doi.org/10.3923/pjbs.2005.1152.1156]
[111]
Fararh, K.M.; Atoji, Y.; Shimizu, Y.; Takewaki, T. Isulinotropic properties of Nigella sativa oil in Streptozotocin plus Nicotinamide diabetic hamster. Res. Vet. Sci., 2002, 73(3), 279-282.
[http://dx.doi.org/10.1016/S0034-5288(02)00108-X] [PMID: 12443686]
[112]
Jouad, H.; Haloui, M.; Rhiouani, H.; El Hilaly, J.; Eddouks, M. Ethnobotanical survey of medicinal plants used for the treatment of diabetes, cardiac and renal diseases in the North centre region of Morocco (Fez–Boulemane). J. Ethnopharmacol., 2001, 77(2-3), 175-182.
[http://dx.doi.org/10.1016/S0378-8741(01)00289-6] [PMID: 11535361]
[113]
El-Mahmoudy, A.; Shimizu, Y.; Shiina, T.; Matsuyama, H.; El-Sayed, M.; Takewaki, T. Successful abrogation by thymoquinone against induction of diabetes mellitus with streptozotocin via nitric oxide inhibitory mechanism. Int. Immunopharmacol., 2005, 5(1), 195-207.
[http://dx.doi.org/10.1016/j.intimp.2004.09.001] [PMID: 15589481]
[114]
Islam, M.N.; Hossain, K.S.; Sarker, P.P.; Ferdous, J.; Hannan, M.A.; Rahman, M.M.; Chu, D.T.; Uddin, M.J. Revisiting pharmacological potentials of Nigella sativa seed: A promising option for COVID-19 prevention and cure. Phytother. Res., 2021, 35(3), 1329-1344.
[http://dx.doi.org/10.1002/ptr.6895] [PMID: 33047412]
[115]
Badary, O.; Hamza, M.S.; Tikamdas, R. Thymoquinone: A promising natural compound with potential benefits for COVID-19 prevention and cure. Drug Des. Devel. Ther., 2021, 15, 1819-1833.
[http://dx.doi.org/10.2147/DDDT.S308863] [PMID: 33976534]
[116]
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(1), 29.
[http://dx.doi.org/10.1186/1472-6882-11-29] [PMID: 21489272]
[117]
Hasan, N.A.; Nawahwi, M.Z.; Ab Malek, H. Antimicrobial activity of Nigella sativa seed extract. Sains Malays., 2013, 42(2), 143-147.
[118]
Rafati, S.; Niakan, M.; Naseri, M. Anti-microbial effect of Nigella sativa seed extract against staphylococcal skin Infection. Med. J. Islam. Repub. Iran, 2014, 28, 42.
[PMID: 25405108]
[119]
Shokri, H. A review on the inhibitory potential of Nigella sativa against pathogenic and toxigenic fungi. Avicenna J. Phytomed., 2016, 6(1), 21-33.
[PMID: 27247919]
[120]
Hannan, A.; Saleem, S.; Chaudhary, S.; Barkaat, M.; Arshad, M.U. Anti bacterial activity of Nigella sativa against clinical isolates of methicillin resistant Staphylococcus aureus. J. Ayub Med. Coll. Abbottabad, 2008, 20(3), 72-74.
[PMID: 19610522]
[121]
Mahmoud, M.R.; El-Abhar, H.S.; Saleh, S. The effect of Nigella sativa oil against the liver damage induced by Schistosoma mansoni infection in mice. J. Ethnopharmacol., 2002, 79(1), 1-11.
[http://dx.doi.org/10.1016/S0378-8741(01)00310-5] [PMID: 11744288]
[122]
Omar, G.H.; Al Hamshary, A.S.; Nagati, I.M.; Eraky, M.A.; Abou-Ouf, E.A.; Kholy, A.A. Effect of Nigella sativa oil on Schistosoma mansoni immature worms in experimentally infected mice. Benha Med. J., 2018, 35(3), 307.
[http://dx.doi.org/10.4103/bmfj.bmfj_2_18]
[123]
Morsi, N.M. Antimicrobial effect of crude extracts of Nigella sativa on multiple antibiotics-resistant bacteria. Acta Microbiol. Pol., 2000, 49(1), 63-74.
[PMID: 10997492]
[124]
Hosseinzadeh, H.; Fazly Bazzaz, B.; Haghi, M.M. Antibacterial activity of total extracts and essential oil of Nigella sativa L. seeds in mice. Pharmacologyonline, 2007, 2, 429-435.
[125]
Nair, M.K.M.; Vasudevan, P.; Venkitanarayanan, K. Antibacterial effect of black seed oil on Listeria monocytogenes. Food Control, 2005, 16(5), 395-398.
[http://dx.doi.org/10.1016/j.foodcont.2004.04.006]
[126]
Chowdhury, A.K.A.; Islam, M.A.; Rashid, M.A.; Ferdous, A.J. Therapeutic potential of the volatile oil of Nigella sativa seeds in monkey model with experimental shigellosis. Phytother. Res., 1998, 12(5), 361-363.
[http://dx.doi.org/10.1002/(SICI)1099-1573(199808)12:5<361:AID-PTR302>3.0.CO;2-1]
[127]
Khan, M.A.U.; Ashfaq, M.K.; Zuberi, H.S.; Mahmood, M.S.; Gilani, A.H. The in vivo antifungal activity of the aqueous extract from Nigella sativa seeds. Phytother. Res., 2003, 17(2), 183-186.
[http://dx.doi.org/10.1002/ptr.1146] [PMID: 12601685]
[128]
Khanna, T.; Zaidi, F.; Dandiya, P. CNS and analgesic studies on Nigella sativa. Fitoterapia-milano, 1993, 64, 407-407.
[129]
Abdel-Fattah, A.F.M.; Matsumoto, K.; Watanabe, H. Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. Eur. J. Pharmacol., 2000, 400(1), 89-97.
[http://dx.doi.org/10.1016/S0014-2999(00)00340-X] [PMID: 10913589]
[130]
MH, B. Comparison of antitussive effect of Nigella sativa with codeine in guinea pig: Iran. J. Basic. Med. Sec., 2005, 28(3), 111-115.
[131]
Al-Ghamdi, M.S. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J. Ethnopharmacol., 2001, 76(1), 45-48.
[http://dx.doi.org/10.1016/S0378-8741(01)00216-1] [PMID: 11378280]
[132]
El-Dakhakhny, M.; Madi, N.J.; Lembert, N.; Ammon, H.P.T. Nigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygenase products in polymorphonuclear leukocytes from rats. J. Ethnopharmacol., 2002, 81(2), 161-164.
[http://dx.doi.org/10.1016/S0378-8741(02)00051-X] [PMID: 12065147]
[133]
Majdalawieh, A.F.; Fayyad, M.W. Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: A comprehensive review. Int. Immunopharmacol., 2015, 28(1), 295-304.
[http://dx.doi.org/10.1016/j.intimp.2015.06.023] [PMID: 26117430]
[134]
Hosseinzadeh, H.; Parvardeh, S.; Nassiri-Asl, M.; Mansouri, M-T. Intracerebroventricular administration of thymoquinone, the major constituent of Nigella sativa seeds, suppresses epileptic seizures in rats. Med. Sci. Monit., 2005, 11(4), 110.
[135]
Malekian, S.; Ghassab-Abdollahi, N.; Mirghafourvand, M.; Farshbaf-Khalili, A. The effect of Nigella sativa on oxidative stress and inflammatory biomarkers: A systematic review and meta-analysis. J. Complement. Integr. Med., 2021, 18(2), 235-259.
[http://dx.doi.org/10.1515/jcim-2019-0198] [PMID: 34187123]
[136]
Mahboubi, M. Natural therapeutic approach of Nigella sativa (Black seed) fixed oil in management of Sinusitis. Integr. Med. Res., 2018, 7(1), 27-32.
[http://dx.doi.org/10.1016/j.imr.2018.01.005] [PMID: 29629288]
[137]
Nasuti, C.; Fedeli, D.; Bordoni, L.; Piangerelli, M.; Servili, M.; Selvaggini, R.; Gabbianelli, R. Anti-inflammatory, anti-arthritic and anti-nociceptive activities of Nigella sativa oil in a rat model of arthritis. Antioxidants, 2019, 8(9), 342.
[http://dx.doi.org/10.3390/antiox8090342] [PMID: 31450670]
[138]
Mansour, M.; Tornhamre, S. Inhibition of 5-lipoxygenase and leukotriene C4 synthase in human blood cells by thymoquinone. J. Enzyme Inhib. Med. Chem., 2004, 19(5), 431-436.
[http://dx.doi.org/10.1080/14756360400002072] [PMID: 15648658]
[139]
Mohamed, A.; Shoker, A.; Bendjelloul, F.; Mare, A.; Alzrigh, M.; Benghuzzi, H.; Desin, T. Improvement of experimental allergic encephalomyelitis (EAE) by thymoquinone; an oxidative stress inhibitor. Biomed. Sci. Instrum., 2003, 39, 440-445.
[PMID: 12724933]
[140]
Ghannadi, A.; Hajhashemi, V.; Jafarabadi, H. An investigation of the analgesic and anti-inflammatory effects of Nigella sativa seed polyphenols. J. Med. Food, 2005, 8(4), 488-493.
[http://dx.doi.org/10.1089/jmf.2005.8.488] [PMID: 16379560]
[141]
Zedlitz, S.; Kaufmann, R.; Boehncke, W.H. Allergic contact dermatitis from black cumin (Nigella sativa) oil-containing ointment. Contact Dermat., 2002, 46(3), 188.
[http://dx.doi.org/10.1034/j.1600-0536.2002.460318.x] [PMID: 12000337]
[142]
Hirschberg, Y.; Shackelford, A.; Mascioli, E.A.; Babayan, V.K.; Bistrian, B.R.; Blackburn, G.L. The response to endotoxin in guinea pigs after intravenous black currant seed oil. Lipids, 1990, 25(8), 491-496.
[http://dx.doi.org/10.1007/BF02538093] [PMID: 2170795]
[143]
Hajhashemi, V.; Ghannadi, A.; Jafarabadi, H. Black cumin seed essential oil, as a potent analgesic and antiinflammatory drug. Phytother. Res., 2004, 18(3), 195-199.
[http://dx.doi.org/10.1002/ptr.1390] [PMID: 15103664]
[144]
Kulyar, M.F.A.; Li, R.; Mehmood, K.; Waqas, M.; Li, K.; Li, J. Potential influence of Nagella sativa (Black cumin) in reinforcing immune system: A hope to decelerate the COVID-19 pandemic. Phytomedicine, 2021, 85, 153277.
[http://dx.doi.org/10.1016/j.phymed.2020.153277] [PMID: 32773257]
[145]
Barakat, E.M.F.; El Wakeel, L.M.; Hagag, R.S. Effects of Nigella sativa on outcome of hepatitis C in Egypt. World J. Gastroenterol., 2013, 19(16), 2529-2536.
[http://dx.doi.org/10.3748/wjg.v19.i16.2529] [PMID: 23674855]
[146]
Onifade, A.A.; Jewell, A.P.; Adedeji, W.A. Nigella sativa Concoction induced sustained seroreversion in HIV patient. Afr. J. Tradit. Complement. Altern. Med., 2013, 10(5), 332-335.
[http://dx.doi.org/10.4314/ajtcam.v10i5.18] [PMID: 24311845]
[147]
Onifade, A.A.; Jewell, A.P.; Okesina, A.B. Seronegative conversion of an HIV positive subject treated with Nigella sativa and honey. Afr. J. Infect. Dis., 2015, 9(2), 47-50.
[http://dx.doi.org/10.4314/ajid.v9i2.6]
[148]
Turhan, Y. Arıcan, M.; Karaduman, Z.O.; Turhal, O.; Gamsızkan, M.; Aydın, D.; Kılıç, B.; Özkan, K. Chondroprotective effect of Nigella sativa oil in the early stages of osteoarthritis: An experimental study in rabbits. J. Musculoskelet. Neuronal Interact., 2019, 19(3), 362-369.
[PMID: 31475944]
[149]
Shahraki, S.; Khajavirad, A.; Shafei, M.N.; Mahmoudi, M.; Tabasi, N.S. Effect of total hydroalcholic extract of Nigella sativa and its n-hexane and ethyl acetate fractions on ACHN and GP-293 cell lines. J. Tradit. Complement. Med., 2016, 6(1), 89-96.
[http://dx.doi.org/10.1016/j.jtcme.2014.11.018] [PMID: 26870685]
[150]
Al-Sheddi, E.S.; Farshori, N.N.; Al-Oqail, M.M.; Musarrat, J.; Al-Khedhairy, A.A.; Siddiqui, M.A. Cytotoxicity of Nigella sativa seed oil and extract against human lung cancer cell line. Asian Pac. J. Cancer Prev., 2014, 15(2), 983-987.
[http://dx.doi.org/10.7314/APJCP.2014.15.2.983] [PMID: 24568529]
[151]
Paramasivam, A.; Sambantham, S.; Shabnam, J.; Raghunandhakumar, S.; Anandan, B.; Rajiv, R.; Vijayashree, P.J.; Jayaraman, G. Anti-cancer effects of thymoquinone in mouse neuroblastoma (Neuro-2a) cells through caspase-3 activation with down-regulation of XIAP. Toxicol. Lett., 2012, 213(2), 151-159.
[http://dx.doi.org/10.1016/j.toxlet.2012.06.011] [PMID: 22732633]
[152]
Ashfaq, S.; Khan, N.T.; Ali, G.M. Nigella sativa (Kalonji), its essential oils and their therapeutic potential. Biomed. J. Sci. Tech. Res., 2021, 33(1), 25448-25454.
[153]
Fararh, K.M.; Shimizu, Y.; Shiina, T.; Nikami, H.; Ghanem, M.M.; Takewaki, T. Thymoquinone reduces hepatic glucose production in diabetic hamsters. Res. Vet. Sci., 2005, 79(3), 219-223.
[http://dx.doi.org/10.1016/j.rvsc.2005.01.001] [PMID: 16054891]
[154]
Karandrea, S.; Yin, H.; Liang, X.; Slitt, A.L.; Heart, E.A. Thymoquinone ameliorates diabetic phenotype in diet-induced obesity mice via activation of SIRT-1-dependent pathways. PLoS One, 2017, 12(9), e0185374.
[http://dx.doi.org/10.1371/journal.pone.0185374] [PMID: 28950020]
[155]
Ahmad, S.; Chughtai, A.; Hussain, R.; Iqbal, S. Physiological and biochemical role of Nigella sativa in hyperlipidemic albino rats a comparative study. Pak. J. Med. Health Sci., 2017, 11, 195-196.
[156]
Kanter, M. Thymoquinone attenuates lung injury induced by chronic toluene exposure in rats. Toxicol. Ind. Health, 2011, 27(5), 387-395.
[http://dx.doi.org/10.1177/0748233710387630] [PMID: 21088054]
[157]
Yimer, E. M.; Tuem, K. B.; Karim, A.; Ur-Rehman, N.; Anwar, F. Nigella sativa L.(black cumin): A promising natural remedy for wide range of illnesses. Evid.-based Complement. Altern. Med., 2019, 2019
[158]
Kolahdooz, M.; Nasri, S.; Modarres, S.Z.; Kianbakht, S.; Huseini, H.F. Effects of Nigella sativa L. seed oil on abnormal semen quality in infertile men: A randomized, double-blind, placebo-controlled clinical trial. Phytomedicine, 2014, 21(6), 901-905.
[http://dx.doi.org/10.1016/j.phymed.2014.02.006] [PMID: 24680621]
[159]
Aleem, U.; Rehman, A.; Shah, R.; Jan, T.; Jan, M.; Jan, R. Effects of thymoquinone obtained from seeds of Nigella sativa on volume & Acidity of stimulated gastric secretion. Pak. J. Med. Health Sci., 2020, 14, 49-50.
[160]
Hosseinzadeh, H.; Parvardeh, S. Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. Phytomedicine, 2004, 11(1), 56-64.
[http://dx.doi.org/10.1078/0944-7113-00376] [PMID: 14971722]
[161]
Ilhan, A.; Gurel, A.; Armutcu, F.; Kamisli, S.; Iraz, M. Antiepileptogenic and antioxidant effects of oil against pentylenetetrazol-induced kindling in mice. Neuropharmacology, 2005, 49(4), 456-464.
[http://dx.doi.org/10.1016/j.neuropharm.2005.04.004] [PMID: 15913671]
[162]
Raza, M.; Alghasham, A.A.; Alorainy, M.S.; El-Hadiyah, T.M. Potentiation of valproate-induced anticonvulsant response by Nigella sativa seed constituents: The role of GABA receptors. Int. J. Health Sci. (Qassim), 2008, 2(1), 15-25.
[PMID: 21475467]
[163]
Al-Jishi, S.A.; Abuo Hozaifa, B. Effect of Nigella sativa on blood hemostatic function in rats. J. Ethnopharmacol., 2003, 85(1), 7-14.
[http://dx.doi.org/10.1016/S0378-8741(02)00356-2] [PMID: 12576196]
[164]
Kacem, R.; Meraihi, Z. Effects of essential oil extracted from Nigella sativa (L.) seeds and its main components on human neutrophil elastase activity. J. Pham. Sec., 2006, 126(4), 301-305.
[http://dx.doi.org/10.1248/yakushi.126.301] [PMID: 16596021]
[165]
Enomoto, S.; Asano, R.; Iwahori, Y.; Narui, T.; Okada, Y.; Singab, A.N.B.; Okuyama, T. Hematological studies on black cumin oil from the seeds of Nigella sativa L. Biol. Pharm. Bull., 2001, 24(3), 307-310.
[http://dx.doi.org/10.1248/bpb.24.307] [PMID: 11256491]
[166]
Asgary, S.; Najafi, S.; Ghannadi, A.; Dashti, G.; Helalat, A. Efficiency of black cumin seeds on hematological factors in normal and hypercholesterolemic rabbits. ARYA Atheroscler., 2012, 7(4), 146-150.
[PMID: 23205047]
[167]
Al-Shaha, O.M.; Mohammed, S.A. Gastro protective effect of oil extract of Nigella sativa seeds against aspirin-induced gastric ulcer in albino rats. J. Entomol. Zool. Stud., 2017, 5(4), 725-732.
[168]
Shakeri, F.; Gholamnezhad, Z.; Mégarbane, B.; Rezaee, R.; Boskabady, M.H. Gastrointestinal effects of Nigella sativa and its main constituent, thymoquinone: A review. Avicenna J. Phytomed., 2016, 6(1), 9-20.
[PMID: 27247918]
[169]
El-Masry, T.A.; Elahwel, A.M.; Emara, A.M. Study on treating ethanol-induced gastric lesions with omeprazole, Nigella sativa oil, or both. Toxicol. Environ. Chem., 2010, 92(9), 1765-1782.
[http://dx.doi.org/10.1080/02772241003730589]
[170]
Mahgoub, A. Thymoquinone protects against experimental colitis in rats. Toxicol. Lett., 2003, 143(2), 133-143.
[http://dx.doi.org/10.1016/S0378-4274(03)00173-5] [PMID: 12749817]
[171]
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(9), 2296-2303.
[http://dx.doi.org/10.1007/s10620-012-2156-x] [PMID: 22476588]
[172]
Salem, A.; Bamosa, A.; Alam, M.; Alshuraim, S.; Alyalak, H.; Alagga, A.; Tarabzouni, F.; Alisa, O.; Sabit, H.; Mohsin, A.; Shaikh, M.; Farea, A.; Alshammari, T.; Obeid, O. Effect of Nigella sativa on general health and immune system in young healthy volunteers; a randomized, placebo-controlled, double-blinded clinical trial. F1000 Res., 2021, 10(1199), 1199.
[http://dx.doi.org/10.12688/f1000research.73524.1]
[173]
Mohamed, A.; Waris, H.M.; Ramadan, H.; Quereshi, M.; Kalra, J. Amelioration of chronic relapsing experimental autoimmune encephalomyelitis (cr-eae) using thymoquinone - biomed 2009. Biomed. Sci. Instrum., 2009, 45, 274-279.
[PMID: 19369775]
[174]
El-Kadi, A. In The black seed (Nigella sative) and immunity: Its effect on human T cell subset. Fed. Proc., 1987, •••, 1222.
[175]
Haq, A.; Lobo, P.I.; Al-Tufail, M.; Rama, N.R.; Al-Sedairy, S.T. Immunomodulatory effect of Nigella sativa proteins fractionated by ion exchange chromatography. Int. J. Immunopharmacol., 1999, 21(4), 283-295.
[http://dx.doi.org/10.1016/S0192-0561(99)00010-7] [PMID: 10408636]
[176]
Xuan, N.; Shumilina, E.; Qadri, S.; Götz, F.; Lang, F. Effect of thymoquinone on mouse dendritic cells. Cell. Physiol. Biochem., 2010, 25(2-3), 307-314.
[http://dx.doi.org/10.1159/000276563] [PMID: 20110691]
[177]
Kalus, U.; Pruss, A.; Bystron, J.; Jurecka, M.; Smekalova, A.; Lichius, J.J.; Kiesewetter, H. Effect of Nigella sativa (black seed) on subjective feeling in patients with allergic diseases. Phytother. Res., 2003, 17(10), 1209-1214.
[http://dx.doi.org/10.1002/ptr.1356] [PMID: 14669258]
[178]
Salem, M.L. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int. Immunopharmacol., 2005, 5(13-14), 1749-1770.
[http://dx.doi.org/10.1016/j.intimp.2005.06.008] [PMID: 16275613]
[179]
El-Mahmoudy, A.; Matsuyama, H.; Borgan, M.A.; Shimizu, Y.; El-Sayed, M.G.; Minamoto, N.; Takewaki, T. Thymoquinone suppresses expression of inducible nitric oxide synthase in rat macrophages. Int. Immunopharmacol., 2002, 2(11), 1603-1611.
[http://dx.doi.org/10.1016/S1567-5769(02)00139-X] [PMID: 12433061]
[180]
Büyüköztürk, S.; Gelincik, A. Özşeker, F.; Genç, S.; Şavran, F.O.; Kıran, B.; Yıllar, G.; Erden, S.; Aydın, F.; Çolakoğlu, B.; Dal, M.; Özer, H.; Bilir, A. Nigella sativa (black seed) oil does not affect the T-helper 1 and T-helper 2 type cytokine production from splenic mononuclear cells in allergen sensitized mice. J. Ethnopharmacol., 2005, 100(3), 295-298.
[http://dx.doi.org/10.1016/j.jep.2005.03.007] [PMID: 16125022]
[181]
Abuharfeil, N.M.; Salim, M.; Von Kleist, S. Augmentation of natural killer cell activity in vivo against tumour cells by some wild plants from Jordan. Phytother. Res., 2001, 15(2), 109-113.
[http://dx.doi.org/10.1002/ptr.692] [PMID: 11268107]
[182]
Akrom, A.; Mustofa, M. Black cumin seed oil increases phagocytic activity and secretion of IL-12 by macrophages. Biomed. Res. (Aligarh), 2017, 28(12), 1-11.
[183]
Wu, D.; Meydani, M.; Leka, L.S.; Nightingale, Z.; Handelman, G.J.; Blumberg, J.B.; Meydani, S.N. Effect of dietary supplementation with black currant seed oil on the immune response of healthy elderly subjects. Am. J. Clin. Nutr., 1999, 70(4), 536-543.
[http://dx.doi.org/10.1093/ajcn/70.4.536] [PMID: 10500023]
[184]
Al-Ankari, A.S. Immunomodulating effects of black seed and oxytetracycline in pigeons. Immunopharmacol. Immunotoxicol., 2005, 27(3), 515-520.
[http://dx.doi.org/10.1080/08923970500242327] [PMID: 16237960]
[185]
Nazrul, I.S.; Begum, P.; Ahsan, T.; Huque, S.; Ahsan, M. Immunosuppressive and cytotoxic properties of Nigella sativa. Phytother. Res., 2004, 18(5), 395-398.
[http://dx.doi.org/10.1002/ptr.1449] [PMID: 15174000]
[186]
Haq, A.; Abdullatif, M.; Lobo, P.I.; Khabar, K.S.A.; Sheth, K.V.; Al-Sedairy, S.T. Nigella sativa: Effect on human lymphocytes and polymorphonuclear leukocyte phagocytic activity. Immunopharmacology, 1995, 30(2), 147-155.
[http://dx.doi.org/10.1016/0162-3109(95)00016-M] [PMID: 8530256]
[187]
El Tahir, K.E.H.; Ashour, M.M.S.; Al-Harbi, M.M. 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(5), 1123-1131.
[http://dx.doi.org/10.1016/0306-3623(93)90359-6] [PMID: 8270171]
[188]
Nickavar, B.; Mojab, F.; Javidnia, K.; Amoli, M.A.R. Chemical composition of the fixed and volatile oils of Nigella sativa L. from Iran. Z. Naturforsch. C J. Biosci., 2003, 58(9-10), 629-631.
[http://dx.doi.org/10.1515/znc-2003-9-1004] [PMID: 14577620]
[189]
Zaoui, A.; Cherrah, Y.; Lacaille-Dubois, M.A.; Settaf, A.; Amarouch, H.; Hassar, M. Diuretic and hypotensive effects of Nigella sativa in the spontaneously hypertensive rat. Therapie, 2000, 55(3), 379-382.
[PMID: 10967716]
[190]
Ramadan, M.F. Introduction to black cumin (Nigella sativa): Chemistry, technology, functionality and applications. Black cumin (Nigella sativa) seeds: Chemistry, Technology, Functionality, and Applications; Springer: Chem, 2021, pp. 1-7.
[http://dx.doi.org/10.1007/978-3-030-48798-0_1]
[191]
Nagi, M.N.; Al-Shabanah, O.A.; Hafez, M.M.; Sayed-Ahmed, M.M. Thymoquinone supplementation attenuates cyclophosphamide-induced cardiotoxicity in rats. J. Biochem. Mol. Toxicol., 2011, 25(3), 135-142.
[http://dx.doi.org/10.1002/jbt.20369] [PMID: 20957680]
[192]
EH,, E.T. Some cardiovascular effects of the dethymoquinonated Nigella sativa volatile oil and its major components a-pinene and p-cymene in rats. SPJ-Saudi Pharm. J., 2003, 11(3), 104-110.
[193]
Hannan, M.A.; Rahman, M.A.; Sohag, A.A.M.; Uddin, M.J.; Dash, R.; Sikder, M.H.; Rahman, M.S.; Timalsina, B.; Munni, Y.A.; Sarker, P.P.; Alam, M.; Mohibbullah, M.; Haque, M.N.; Jahan, I.; Hossain, M.T.; Afrin, T.; Rahman, M.M.; Tahjib-Ul-Arif, M.; Mitra, S.; Oktaviani, D.F.; Khan, M.K.; Choi, H.J.; Moon, I.S.; Kim, B. Black cumin (Nigella sativa L.): A comprehensive review on phytochemistry, health benefits, molecular pharmacology, and safety. Nutrients, 2021, 13(6), 1784.
[http://dx.doi.org/10.3390/nu13061784] [PMID: 34073784]
[194]
Mashayekhi-Sardoo, H.; Rezaee, R.; Karimi, G. Nigella sativa (black seed) safety: An overview. Asian Biomed., 2020, 14(4), 127-137.
[http://dx.doi.org/10.1515/abm-2020-0020]
[195]
Ali, B.; Blunden, G. Pharmacological and toxicological properties of Nigella sativa. Phytother. Res., 2003, 17(4), 299-305.
[196]
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.
[http://dx.doi.org/10.1078/0944-7113-00084] [PMID: 11924767]
[197]
Mashayekhi-Sardoo, H.; Rezaee, R.; Karimi, G. An overview of in vivo toxicological profile of thymoquinone. Toxin Rev., 2018.
[198]
Steinmann, A.; Schätzle, M.; Agathos, M.; Brett, R. Allergic contact dermatitis from black cumin (Nigella sativa) oil after topical use. Contact Dermat., 1997, 36(5), 268-269.
[http://dx.doi.org/10.1111/j.1600-0536.1997.tb00219.x] [PMID: 9197967]

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