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Nigella sativa (black seed) safety: an overview

Habibeh Mashayekhi-Sardoo
Habibeh Mashayekhi-Sardoo
, 
Ramin Rezaee
Ramin Rezaee
 and 
Gholamreza Karimi
Gholamreza Karimi
   | Sep 20, 2020
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Article Category: Review
Published Online: Sep 20, 2020
Page range: 127 - 137
DOI: https://doi.org/10.1515/abm-2020-0020
Keywords
© 2020 Habibeh Mashayekhi-Sardoo et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1

Main bioactive components of N. sativa: (A) carvacrol (5-isopropyl-2-methylphenol; National Center for Biotechnology Information. PubChem Database compound identification number [CID] 10364), (B) 4-cymene (4-isopropyltoluene; CID 7463), (C) thymoquinone (4-cymene-2,5-dione; CID 10281), (D) nigellidine (CID 136828302), (E) nigellicine (CID 11402337), and (F) α-hederin (CID 73296).
Main bioactive components of N. sativa: (A) carvacrol (5-isopropyl-2-methylphenol; National Center for Biotechnology Information. PubChem Database compound identification number [CID] 10364), (B) 4-cymene (4-isopropyltoluene; CID 7463), (C) thymoquinone (4-cymene-2,5-dione; CID 10281), (D) nigellidine (CID 136828302), (E) nigellicine (CID 11402337), and (F) α-hederin (CID 73296).

Figure 2

Various toxicities reported for N. sativa. Abbreviations: γ-GT, gamma-glutamyl transferase; ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate aminotransferase; PT, prolonged prothrombin time; APTT, activated partial thromboplastin time; TT, thrombin time; ATIII, antithrombin III; RBCs, red blood cells; Hb, hemoglobin; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; PCV, packed cell volume; MCV, mean corpuscular volume; Plt, platelet; Hct, hematocrit; MGV, mean globular volume; PARP, poly(ADP-ribose) polymerase.
Various toxicities reported for N. sativa. Abbreviations: γ-GT, gamma-glutamyl transferase; ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate aminotransferase; PT, prolonged prothrombin time; APTT, activated partial thromboplastin time; TT, thrombin time; ATIII, antithrombin III; RBCs, red blood cells; Hb, hemoglobin; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; PCV, packed cell volume; MCV, mean corpuscular volume; Plt, platelet; Hct, hematocrit; MGV, mean globular volume; PARP, poly(ADP-ribose) polymerase.

Subacute toxicity of Nigella sativa in animal studies

Substance/doseAnimals usedExposure periodObservation periodMain resultsReference
N. sativa seeds AE 10 mL/kg, p.o.Male Sprague Dawley rats14 days30 days↑ Serum γ-GT and ALT levels. Unchanged serum ALP levels and histopathological examinations[63]
N. sativa seed oil 10 mL/kg, p.o.Rats48 hNot specifiedNo toxicity[53]
Mice
N. sativa seeds AE, ME, and CE 6 g/kg, p.oBoth sexes of young virgin mice14 daysSame 14 daysNo toxicity wide margin of safety[4]
N. sativa powder 90, 180, 360, and 540 mg/kg, locallyNormal adult male albino rats1, 2, and 4 weeksSame 4 weeksTransient alterations in both anticoagulant and coagulant functions[54]
N. sativa powder 0.01, 0.1, and 1 g/kg/day, p.oMale Sprague Dawley rats28 daysSame 28 daysNo toxicity[64]
N. sativa AE 2, 6.4, 21, 33, and 60 g/kg, orally), p.oMus musculus6 weeksSame 6 weeks21 g/kg: hepatotoxic 60 g/kg: high mortality[65]
mice
BSH 100, 500, 1,000, and 2,000 mg/kg, p.oMale Sprague Dawley rats14 days28 daysNo toxicity[66]

Cytotoxic and genotoxic properties of Nigella sativa in vitro

SubstanceConcentration periodPeriodCell typeMain resultsReference
N. sativa oil0.25, 0.5, and 1 μg/mL95 hGingival fibroblastsNo cytotoxicity[67]
N. sativa EE0–2 mg/mL24 hRat L6 muscle cell lineHepG2 cell lineEC50 >2,000 μg/mL against L6myc cell linesEC50 >1,470 μg/mL against HepG2 cell lines[68]
N. sativa EE100, 500, and 1,000 μg/mL48 hIsolated rat splenocytesCytotoxic effects at 500 and 1,000 μg/mL[57]
N. sativa EO and ME, PE, CE, AE, and ether extract10, 100, and 1,000 μg/mL24 hBSLHigher toxicity by chloroform and petroleum ether extracts.LC50 petroleum ether: 7 μg/mLLC50 chloroform: 21 μg/mL[69]
N. sativa seed VO500, 250, 125, and 62.5 μg/mLNot specifiedSCL, SCL-6, SCL-37′6, NUGC-4, Kato-3, 3T6LC50 SCL 155.02 μg/mLLC50 SCL-6 185.77 μg/mLLC50 SCL-37′6 120.40 μg/mLLC50 NUGC-4 384.53 μg/mLLC50 3T6 286.83 μg/mL[70]
N. sativa PE and AE670 μg/mL24 hHL60IC50 PE 654 μg/mLIC50 AE >1,000 μg/ml[71]
N. sativa EO100 mg/mL24 hHuh7 human cellsNo cytotoxicity[72]
N. sativa seed oil50–500 μg/mLU-1242, U251, U-87, U-373, A172 and SNB19IC50 260 μg/mL[58]
AE of N. sativa0.5, 1, 4, 8, 9, and 18 mg/mLHuman C3A cellsPositive micronucleus test extract from Setta[73]
N. sativa seed ME, NE, and CE2, 2.25, 2.5, 2.75, and 3 μg/mL of methanolic, n-hexane.0.25, 0.5, 0.75, and 1 ng/mL of chloroform24 hHeLa cellsIC50 methanolic: 2.28 μg/mLIC50 n-hexane 2.20 μg/mLIC50 chloroform 0.41 ng/mL[74]
N. sativa AE79.5 μg/mL48 hF 344 hepatocytes treated with MNNG↑ Chromosomal aberrations[59]

Acute toxicity of Nigella sativa in animal studies

Substance/doseAnimals usedObservation periodLD50Reference
N. sativa seed VO, FO, and AE, i.p.SWR mice24 hAE: 3,020 mg/kgVO: 1,853 mg/kgFO: 3,371 mg/kg[51]
N. sativa seed FO 0.25, 0.5, 1, 2, 3, 4, and 6 mL/kg, i.p.Both sexes of mice15 days2.06 mL/kg[49]
N. sativa seed FO 10, 15, 20, 25, 30, 40, and 50 mL/kg, p.o28.8 mL/kg
N. sativa seeds AE, ME and CE 6, 9, 14 and 21 g/kg, p.o.Both sexes of young virgin mice7 daysNo mortality[4]
N. sativa EO 0.2, 0.4, 0.4, 0.8, 1 mg/kg, p.o.Both sexes of white Wistar rats and NMRINot specifiedNo mortality[62]

Subchronic toxicity of Nigella sativa in animal studies

Substance/doseAnimals usedExposure periodObservation periodMain resultsReference
N. sativa seeds 20 and 100 g/kg, p.o.7-day-old Hibro broiler chicks7 weeksSame 7 weeksNo toxicity[55]

Chronic toxicity of Nigella sativa in animal studies

Substance/doseAnimals usedExposure periodObservation periodMain resultsReference
N. sativa FO 2 mL/kg, p.o.Wistar-Kyoto rats12 weeksSame 12 weeks↓ Leukocyte and Plt↑ HCT, Hb, MGV, MCH, and MCHCNo alteration in AST, ALT, ALP, and GGT levels or histopathological featuresSlight toxicity[49]
N. sativa FO 1 mL/kg, p.o.Wistar-Kyoto rats12 weeksSame 12 weeks↓ Leukocyte and Plt↑ HCT, HbNo alteration in AST, ALT, ALP, and GGT levelsSlight toxicity[56]

Nigella sativa toxicity in humans

SubstanceConcentrationExposure route/periodCase historyMain resultsReference
Pure oil of black cuminNot specifiedUsed on the neck for 3 months28-year-old man for treatment of sore throatAllergic contact dermatitis[60]
EO of the seeds of black cuminNot specifiedRepeatedly applied as an ointment31-year-old woman with an 8-month history of eczema on both handsAllergic contact dermatitis[61]
Capsules of BCEOContaining 500 mg of organic N. sativa oil and 7.5 mg of vitamin EDaily 15 days56-year-old womanSevere bullous target-like lesions, compatible with erythema multiforme[80]
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