A review on the inhibitory potential of Nigella sativa against pathogenic and toxigenic fungi

Document Type : Review Article


Faculty of Veterinary Medicine, Amol University of Special Modern Technologies, Amol, Iran


Nigella sativa (N. sativa) grows in various parts of the world, particularly in Iran. It has been traditionally used as a folk remedy to treat a number of diseases. The seeds of this plant contain moisture, proteins, carbohydrates, crude fiber, alkaloids, saponins, ash, fixed oils and essential oil. The major components of the essential oil are thymoquinone, p-cymene, trans-anethole, 2-methyl-5(1-methyl ethyl)-Bicyclo[3.1.0]hex-2-en and γ-terpinene. So far, several pharmacological effects such as anti-oxidant, anti-inflammatory, anti-cancer and anti-microbial have been reported for N. sativa or its active compounds. Thymoquinone, thymohydroquinone and thymol are the most active constituents which have different beneficial properties. The oil, extracts and some of N. sativa active components possessed moderate in vitro and in vivo inhibitory activity against pathogenic yeasts, dermatophytes, non-dermatophytic filamentous fungi and aflatoxin-producing fungi. The main morphological changes of pathogenic and toxigenic fungi treated with N. sativa oil were observed in the cell wall, plasma membrane and membranous organelles, particularly in the nuclei and mitochondria. Although this review represents first step in the search for a new anti-fungal drug, the full potential of N. sativa as a fungitoxic agent has not been exploited and necessitates further investigations.


Main Subjects

Abdel-Wahhab MA, Aly SE. 2005. Antioxidant property of Nigella sativa (black cumin) and Syzygium aromaticum (clove) in rats during aflatoxicosis. J Appl Toxicol, 25: 218-223.
Adamu HM, Ekanem EO, Bulama S. 2010. Identification of essential oil components from Nigella sativa seed by gas chromatography-mass spectroscopy. Pak J Nutr, 9: 966-967.
Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F. 2013. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed, 3: 337-352.
Al-Ghasham A,  Ata HS, El-Deep S,  Meki A, Shehada S. 2008. Study of protective effect of date and Nigella sativa on aflatoxin B1 toxicity. Int J Health Sci, 2: 26-44.
Ali B, Blunden G. 2003. Pharmacological and toxicological properties of Nigella sativa. Phytother Res, 17: 299-305.
Ali Z, Ferreira D, Carvalho P, Avery MA, Khan IA. 2008. Nigellidine-4-O-sulfite, the first sulfated indazole-type alkaloid from the seeds of Nigella sativa. J Nat Prod, 71: 1111-1112.
Aljabre SH, Randhawa MA, Akhtar N, Alakloby OM, Alqurashi AM, Aldossary A. 2005. Antidermatophyte activity of ether extract of Nigella sativa and its active principle, thymoquinone. J Ethnopharmacol, 101: 116-119.
Al-Jassir MS. 1992. Chemical composition and microflora of black cumin (Nigella sativa L.) seeds growing in Saudi Arabia. Food Chem, 45: 239-242.
Al Saleh IA, Billedo G, Inam IE. 2006. Level of selenium, DL-α-tocopgerol, DL-γ- tocopherol, all trans retinol, thymoquinone and thymol in different brands of Nigella sativa seeds. J Food Comp Anal, 19: 167-175.
Amara AA, El-Masry MH, Bogdady HH. 2008. Plant crude extracts could be the solution: extracts showing in vivo antitumorigenic activity. Pak J Pharm Sci, 21: 159-171.
Asdadi A, Harhar H, Gharby S, Bouzoubaâ Z, Yadini AE, Moutaj R, Hadek ME, Chebli B, Hassani LMI. 2014. Chemical composition and antifungal activity of Nigella Sativa L. oil seed cultivated in Morocco. Int J Pharma Sci Invent, 3: 9-15.
Atta MB. 2003. Some characteristics of Nigella (Nigella sativa L.) seed cultivated in Egypt and its lipid profile. Food Chem, 83: 63-68.
Atta-Ur-Rahman. 1995. Nigellidine-a new indazole alkaloid from the seed of Nigella sativa. Tetrahedron Lett, 36: 1993-1994.
Badary OA, Abdel-Naim AB, Abdel-Wahab MH, Hamada FM. 2000. The influence of thymoquinone on doxorubicin-induced hyperlipidemic nephropathy in rats. Toxicol, 143: 219-226.
Boskabady MH, Mohsenpoor N, Takaloo L. 2010. Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomed, 17: 707-713.
Bathnagar D, Garcia S. 2001. Aspergillus. In Labbe RG, Garcia S. (Eds.), Guide to Foodborne Pathogens. New York: John Wiley and Sons, pp. 35-49.
Burits M, Bucar F. 2000. Anti-oxidant activity of Nigella sativa oil. Phytother Res, 14: 323-328.
Cavaleiro C, Pinto E, Goncalves MJ, Salgueiro L. 2006. Antifungal activity of Juniperus essential oils against dermatophyte, Aspergillus and Candida strains. J Appl Microbiol, 100: 1333-1338.
Cheikh-Rouhou S, Besbes S, Lognay G, Blecker C, Deroanne C, Attia H. 2008. Sterol composition of black cumin (Nigella sativa L.) and Aleppo pine (Pinus halpensis Mill.) seed oils. J Food Comp Anal, 21: 162-168.
Cosentino S, Tuberoso CIG, Pisano B. 1999. In-vitro antimicrobial activity and chemical composition of Sardinian Thymus essential oils. Lett Appl Microbiol, 29: 130-136.
Daferera DJ, Zirgas BN, Polission MG. 2000. GC-MS analysis of essential oil from some Greek aromatic plants and their fungitoxicity on Penicillium digitatum. J Agric Food Chem, 48: 2576-2581.
Douglas LJ. 2003. Candida biofilms and their role in infection. Trends Microbiol, 11: 30-36.
Duarte MCT, Figueira GM. 2008. Anti-Candida activity of essential oils and extracts from native and exotic medicinal plants used in Brazil. In: Rai MK, Carpinella C. (Eds.), Naturally Occurring Bioactive Compounds: A Newer and Safer Alternative for Control of Pest and Diseases. The Haworth Press Inc.
El-Nagerabi SAF, Al-Bahry SN, Elshafie AE, Al-Hilali S. 2012. Effect of Hibiscus sabdariffa extract and Nigella sativa oil on the growth and aflatoxin B1 production of Aspergillus flavus and Aspergillus parasiticus strains. Food Control, 25: 59-63.
El-Tahir KE, Bakheet DM. 2007. The black seed Nigella sativa linnaeus-a mine for multi-cures: A plea for urgent clinical evaluation of its volatile oil. J T U Med Sci, 1: 1-19.
El-Wakil SS. 2007. Evaluation of the in vitro effect of Nigella sativa aqueous extract on Blastocystis hominis isolates. J Egypt Soc Parasitol, 7: 801-813.
Fan JJ, Chen.JH. 1999. Inhibition of aflatoxin-producing by welsh onion extracts. J Food Prot, 62: 414-417.
Feldmesser M. 2003. New and emerging antifungal agents: Impact on respiratory infections. Am J Respir Med, 2: 371-383.
Fierro M, Fidalgo CB. 1996. The involvement of nitrous oxide in the anti-Candida albicans activity of rat neutrophils. Immunol, 89: 295-300.
Iheshiulor OOM, Esonu BO, Chuwuka OK, Omede AA, Okoli IC, Ogbuewu IP. 2011. Effects of mycotoxins in animal nutrition. Asian J Anim Sci, 5: 19-33.
Junemann M. 1998. Three great healing herbs, Lotus Light Publications, Twin Laked,WI, pp. 45.
Gerige SJ, Gerige MKY, Rao M. 2009. GC-MS Analysis of Nigella sativa seeds and antimicrobial activity of its volatile oil. Braz Arch Biol Technol, 52: 1189-1192.
Geweely NS, Alakilli SYM. 2012. Effect of the purification of antidermatophytic proteins from Nigella sativa on four zoophilic species. Afr J Biotechnol, 11: 9422-9434.
Golparvar AR, Ghaisari MM, Hadipanah A, Armin A. 2013. Chemical analysis and identification of the components of black seed and Thyme cultivated in Iran. Sci Agri, 4: 55-57.
Goreja WG. 2003. Black seed: Nature's Miracle Remedy, Amazing Herbs Press, New York, NY.
Gupta S, Satishkumar MN, Duraiswamy B, Das S, Chhajed M. 2012. Potential herbs and its phytoconstituents against fungal infection: A systematic review. World J Pharma Res, 1: 1-20.
Halamova K, Kokoska L, Flesar J, Sklenickova O, Svobodova B, Marsik P. 2010. In vitro antifungal effect of black cumin seed quinones against dairy spoilage yeasts at different acidity levels. J Food Prot, 73: 2291-2295.
Hussein SY, Mekkawy IAA, Moktar ZZ Mubarak M. 2000.  Protective effect of Nigella sativa seed against aflatoxicosis in Oreochromis niloticus.  Proc. Conf. Mycotoxins and Dioxins and the Environment, Bydgoszcz, 25-27 Sept., pp: 109-130.
Ivankovic SR, Stojkovic M, Jukic M, Milos M. 2006. The antitumor activity of thymoquinone and thymohydroquinone in vitro and in vivo. Exp Oncol, 28: 220-224.
Kauffman CA. 2006. Fungal infections. Proc Am Thorac Soc, 3: 35-40.
Khan MA, Ashfaq MK, Zuberi HS, Zuberi AH. 2003. The in vivo anti-fungal activity of the aqueous extract from Nigella sativa seed. Phytother Res, 17: 183-186.
Khosravi AR, Minooeianhaghighi MH, Shokri H, Emami SA, Alavi SM, Asili J. 2011. The potential inhibitory effect of Cuminum cyminum, Ziziphora clinopodioides and Nigella sativa essential oils on the growth of Aspergillus fumigatus and Aspergillus flavus. Braz J Microbiol, 42: 216-224.
Khosravi AR, Shokri H, Farahnejat Z, Chalangari R, Katalin M. 2013. Antimycotic efficacy of Iranian medicinal plants towards dermatophytes obtained from patients with dermatophytosis. Chinese J Nat Med, 11: 43-48.
Khosravi AR, Shokri H, Minooeianhaghighi M. 2011. Inhibition of aflatoxin production and growth of Aspergillus parasiticus by Cuminum cyminum, Ziziphora clinopodioides, and Nigella sativa essential oils. Foodborne Pathog Dis, 8: 1275-1280.
Kumar R, Mishra AK, Dubey NK, Tripathi YB. 2007. Evaluation of Chenopodium ambrosioides as a potential source of antifungal, antiaflatoxigenic and antioxidant activity. Int J Food Microbiol, 115: 159-164.
Mahmoudvand H, Sharifi I, Fasihi Harandi M, Shokohi M, Shakibaie M, Rezaei Riabi T. 2014. Anti-leishmania effects of methotrexate (MTX) alone and incombination with meglumine antimoniate (MA) against Iranian isolate of sensitive and MA-resistant Leishmania tropica: an in-vitro assay. Asian Pac J Trop Med, 4: 412-420.
Mahmoud MR, El-Abhar HS, Saleh S. 2002. The effects of Nigella sativa oil against the liver damage induced by Schistosoma mansoni in mice. J Ethnopharmacol, 79: 1-11.
Maraqa A, Al-Sharoa NF, Farah H, Elbjeirami WM, Shakya AK, Sallal AJ. 2007. Effect of Nigella sativa extract and oil on aflatoxin production by Aspergillus flavus. Turk J Biol, 31: 155-159.
Mariam A, Al-Basal A. 2009. In vitro and in vivo anti-microbial effects of Nigella sativa Linn. seed extracts against clinical isolates from skin wound infections. Am J Appl Sci, 6: 1440-1447.
Martinez-Rossi NM, Peres NTA, Rossi A. 2008. Antifungal resistance mechanisms in dermatophytes. Mycopathologia, 166: 369-383.
Mehta BK, Pandit V, Gupta M. 2009. New principles from seeds of Nigella sativa. Nat Prod Res, 23: 138-148.
Morikawa T, Xu F, Ninomiya K, Matsuda H, Yoshikawa M. 2004. N. mines A3, A4, A5 and C, new dolabellane-type diterpene alkaloids with lipid metabolism-promoting activities from the Egyptian medicinal food black cumin. Chem Pharm Bull, 52: 494-497.
Naeini A, Khosravi AR, Chitsaz M, Shokri H, Kamlnejad M. 2009. Anti-Candida albicans activity of some Iranian plants used in traditional medicine. J Mycol Méd, 19: 168-172.
Nasir Z, Abid AR, Hayat Z, Shakoor HI. 2005. Effect of kalongi (Nigella sativa) seeds on egg production and quality in white Leghorn layers. J Anim Plant Sci, 15: 22-24.
Nergiz C, Otles S. 1993. Chemical composition of Nigella sativa L. seeds. Food Chem, 48: 259-261.
Nickavar B, Mojab F, Javidnia K, Amoli MA. 2003. Chemical composition of the fixed and volatile oils of Nigella sativa L. from Iran. Z Naturforsch C, 58: 629-631.
Ouraïni D, Agoumi A, Ismaili-Alaoui M, Alaoui K, Cherrah Y, Alaoui MA, Belabbas MA. 2007. Activité antifongique de l’acide oléique et des huiles essentielles de Thymus saturejoides L. et de Mentha pulegium L., comparée aux antifongiques dans les dermatoses mycosiques. Phytothér, 5: 6-14.
Ozmen A, Gamze B, Tugba A. 2007. Antimitotic and antibacterial effects of the Nigella sativa L Seed. Cayologial, 60: 270-272.
Pina-Vaz C, Rodrigues AG, Pinto E, Costa-de-Oliveira S, Tavares C, Salgueiro LR, Cavaleiro C, Goncalves MJ, Martinez-de-Oliveira J. 2004. Antifungal activity of Thymus oils and their major compounds. J Eur Acad Dermatol, 18: 73-78.
Pinto E, Palmeira A, Salgueiro L, Cavaleiro C, Goncalves MJ, Pina-Vaz C, Rodrigues A, Oliveira S. 2003. Antifungal activity of oregano oils (Lippia graveolens and Origanum virens) on dermatophyte species. Clin Microbiol Infec, 9: 222-230.
Rapp RP. 2004. Changing strategies for the management of invasive fungal infections. Pharmacother, 24: 4S-28S.
Rasooli I, Razzaghi-Abyaneh M. 2004. Inhibitory effects of thyme oils on growth and aflatoxin production by Aspergillus parasiticus. Food Control, 1: 479-483.
Raval BP, Shah TG, Suthar MP, Ganure AL. 2010. Screening of Nigella Sativa Seeds for antifungal activity. Ann Biolog Res, 1: 164-171.
Rchid H, Chevassus H, Nmila R, Guiral C, Petit P, Chokairi M. 2004. Nigella sativa seed extracts enhance glucose-induced insulin release from rat-isolated langerhans islets. Fundam Clin Pharmacol, 18: 525-529.
Randhawa MA, Al-Ghamdi MS. 2002. A review of the pharmacothera peutic effects of Nigella sativa. Pak J Med Res, 41: 77-83.
Rogozhin EA, Oshchepkova YI, Odintsova TI, Khadeeva NV, Veshkurova ON, Egorov TA. 2011. Novel antifungal defensins from Nigella sativa L. seeds. Plant Physiol Biochem, 49: 131-137.
 Roze LV, Koptina AV, Laivenieks M, Beaudry RM, Jones DA, Kanarsky AV, Linz JE. 2011. Willow volatiles influence growth, development, and secondary metabolism in Aspergillus parasiticus.  Appl Microbiol Biotechnol, 92: 359-370.
Sakuda S, Ono M, Ikeda H, Nakamura T, Inagaki Y, Kawachi R, Nakayama J, Suzuki A, Isogai A, Nagasawa H. 2000. Blasticidin A as an inhibitor of aflatoxin production by Aspergillus parasiticus. J Antibiotics, 68: 407-412.
Salem ML 2005. Immunomodulatory and therapeutic properties of the Nigella Sativa L. Seed. Int Immunopharmacol, 5: 1749-1770.
Shigeharu I, Katsuhisa U, Toshio T, Hideyo Y, Shigeru A. 2006. Evaluation of the effect of terpenoid quinones on Trichophyton mentagrophytes by solution and vapor contact. J Infect Chemother, 12: 100-104.
Shohayeb M, Halawani E. 2012. Comparative antimicrobial activity of some active constituents of N. sativa L. World Appl Sci J, 20: 182-189.
Shokri H, Sharifzadeh A, Ashrafi Tamai I. 2012. Anti-Candida zeylanoides activity of some Iranian plants used in traditional medicine. J Mycol Méd, 22: 211-216.
Sidat MM, Correia D, Buene TP. 2006. Tinea capitis among rural school children of the district of Magude, in Maputo province, Mozambique. Mycoses, 49: 480-483.
Singh G, Marimuthu P, de Heluani CS, Catalan C. 2005. Chemical constituents and antimicrobial and antioxidant potentials of essential oil and acetone extract of Nigella sativa seeds. J Sci Food Agric, 85: 2297-2306.
Singh SS, Singh DG, Schuff C, de Lampasona MP, Catalán CAN. 2015. Composition, in vitro antioxidant and antimicrobial activities of essential oil and oleoresins obtained from black cumin seeds (Nigella sativa L.). BioMed Res Int, In Press.
Sitara U, Niaz I, Naseem J, Sultana N. 2008. Antifungal effect of essential oils on in vitro growth of pathogenic fungi. Pak J Bot, 40: 409-414.
Sitheeque MAM, Panagoda GJ, Yau J, Amarakoon AMT, Udagama URN, Samaranayake LP. 2009. Antifungal activity of black tea polyphenols (catechins and thea flavins) against Candida Species. Chemother, 55: 189-196.
Staphylakis PK, Gegiou D. 1986. The sterols of Nigella sativa seed oil. Phytochem, 25: 761-763.
Sultan MT, Butt MS, Anjum FM, Jamil A, Akhtar S, Nasir M. 2009. Nutritional profile of indigenous cultivar of black cumin seeds and antioxidant potential of its fixed and essential oil. Pak J Bot, 41: 1321-1330.
Sunita M, Meenakshi S. 2013. Chemical composition and antidermatophytic activity of Nigella sativa essential oil. Afr J Pharma Pharmacol, 7: 1286-1292.
Taha M, Abdel Azeiz AZ, Saudi W. 2010. Antifungal effect of thymol, thymoquinone and thymohydroquinone against yeasts, dermatophytes and non-dermatophyte molds isolated from skin and nails fungal infections. Egypt J Biochem Mol Biol, 28: 109-126.
Takruri HRH, Dameh MAF. 1998. Study of nutritional value of black cumin seeds (Nigella sativa L.). J Sci Food Agric, 76: 404-410.
Toma CC, Simu GM, Hanganu M, Olah N, Vata FMG, Hammami C, Hammami M. 2010. Chemical composition of the Tunisian Nigella sativa. Note I. Profile on essential oil. Farmacia, 58: 458-464.
Uz E, BayraK O, Uz E, Kaya A, Baayrak R. 2008. Nigella sativa oil for prevention of chroniccyclosporine nephrotoxicity: An experimental model. Am J Nephrol, 28: 517-522.
Venkatachallam UKT, Pattekhan H, Divakar S, Kadimi US. 2010. Chemical composition of Nigella sativa L. seed extracts obtained by supercritical carbon dioxide. J Food Sci Technol, 47: 598-605.
Yahyaraeyat R, Khosravi AR, Shahbazzadeh D, Khalaj V. 2013. The potential effects of Zataria multiflora Boiss essential oil on growth, aflatoxin production and transcription of aflatoxin biosynthesis pathway genes of toxigenic Aspergillus parasiticus. Braz J Microbiol, 44: 649-655.
Yoshinari T, Akiyama T, Nakamura K, Kondo T, Takahashi Y, Muraoka Y, Nonomura Y, Nagasawa H, Sakuda S. 2007. Dioctatin A is a strong inhibitor of aflatoxin production by Aspergillus parasiticus. Microbiol, 153: 2774-2780.
Youssef MKE, Eshak NS, Hana RS. 2013. Physicochemical characteristics, nutrient content and fatty acid composition of Nigella sativa oil and sesame oil. Food Pub Health, 3: 309-314.
Zaoui A, Cherrah Y, Lacaille-Dubois MA, Settaf A, Amarouch H, Hassar M. 2000. Diuretic and hypotensive effects of Nigella sativa in the spontaneously hypertensive rat. Therapie, 55: 379-382.