Nigella sativa (black seed) safety: an overview

Figure 1

Figure 2

Subacute toxicity of Nigella sativa in animal studies

Substance/dose	Animals used	Exposure period	Observation period	Main results	Reference
N. sativa seeds AE 10 mL/kg, p.o.	Male Sprague Dawley rats	14 days	30 days	↑ Serum γ-GT and ALT levels. Unchanged serum ALP levels and histopathological examinations	[63]
N. sativa seed oil 10 mL/kg, p.o.	Rats	48 h	Not specified	No toxicity	[53]
	Mice
N. sativa seeds AE, ME, and CE 6 g/kg, p.o	Both sexes of young virgin mice	14 days	Same 14 days	No toxicity wide margin of safety	[4]
N. sativa powder 90, 180, 360, and 540 mg/kg, locally	Normal adult male albino rats	1, 2, and 4 weeks	Same 4 weeks	Transient alterations in both anticoagulant and coagulant functions	[54]
N. sativa powder 0.01, 0.1, and 1 g/kg/day, p.o	Male Sprague Dawley rats	28 days	Same 28 days	No toxicity	[64]
N. sativa AE 2, 6.4, 21, 33, and 60 g/kg, orally), p.o	Mus musculus	6 weeks	Same 6 weeks	21 g/kg: hepatotoxic 60 g/kg: high mortality	[65]
	mice
BSH 100, 500, 1,000, and 2,000 mg/kg, p.o	Male Sprague Dawley rats	14 days	28 days	No toxicity	[66]

Cytotoxic and genotoxic properties of Nigella sativa in vitro

Substance	Concentration period	Period	Cell type	Main results	Reference
N. sativa oil	0.25, 0.5, and 1 μg/mL	95 h	Gingival fibroblasts	No cytotoxicity	[67]
N. sativa EE	0–2 mg/mL	24 h	Rat L6 muscle cell lineHepG2 cell line	EC50 >2,000 μg/mL against L6myc cell linesEC50 >1,470 μg/mL against HepG2 cell lines	[68]
N. sativa EE	100, 500, and 1,000 μg/mL	48 h	Isolated rat splenocytes	Cytotoxic effects at 500 and 1,000 μg/mL	[57]
N. sativa EO and ME, PE, CE, AE, and ether extract	10, 100, and 1,000 μg/mL	24 h	BSL	Higher toxicity by chloroform and petroleum ether extracts.LC50 petroleum ether: 7 μg/mLLC50 chloroform: 21 μg/mL	[69]
N. sativa seed VO	500, 250, 125, and 62.5 μg/mL	Not specified	SCL, SCL-6, SCL-37′6, NUGC-4, Kato-3, 3T6	LC50 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 AE	670 μg/mL	24 h	HL60	IC50 PE 654 μg/mLIC50 AE >1,000 μg/ml	[71]
N. sativa EO	100 mg/mL	24 h	Huh7 human cells	No cytotoxicity	[72]
N. sativa seed oil	50–500 μg/mL		U-1242, U251, U-87, U-373, A172 and SNB19	IC50 260 μg/mL	[58]
AE of N. sativa	0.5, 1, 4, 8, 9, and 18 mg/mL		Human C3A cells	Positive micronucleus test extract from Setta	[73]
N. sativa seed ME, NE, and CE	2, 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 chloroform	24 h	HeLa cells	IC50 methanolic: 2.28 μg/mLIC50 n-hexane 2.20 μg/mLIC50 chloroform 0.41 ng/mL	[74]
N. sativa AE	79.5 μg/mL	48 h	F 344 hepatocytes treated with MNNG	↑ Chromosomal aberrations	[59]

Acute toxicity of Nigella sativa in animal studies

Substance/dose	Animals used	Observation period	LD50	Reference
N. sativa seed VO, FO, and AE, i.p.	SWR mice	24 h	AE: 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 mice	15 days	2.06 mL/kg	[49]
N. sativa seed FO 10, 15, 20, 25, 30, 40, and 50 mL/kg, p.o			28.8 mL/kg
N. sativa seeds AE, ME and CE 6, 9, 14 and 21 g/kg, p.o.	Both sexes of young virgin mice	7 days	No 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 NMRI	Not specified	No mortality	[62]

Subchronic toxicity of Nigella sativa in animal studies

Substance/dose	Animals used	Exposure period	Observation period	Main results	Reference
N. sativa seeds 20 and 100 g/kg, p.o.	7-day-old Hibro broiler chicks	7 weeks	Same 7 weeks	No toxicity	[55]

Chronic toxicity of Nigella sativa in animal studies

Substance/dose	Animals used	Exposure period	Observation period	Main results	Reference
N. sativa FO 2 mL/kg, p.o.	Wistar-Kyoto rats	12 weeks	Same 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 rats	12 weeks	Same 12 weeks	↓ Leukocyte and Plt↑ HCT, HbNo alteration in AST, ALT, ALP, and GGT levelsSlight toxicity	[56]

Nigella sativa toxicity in humans

Substance	Concentration	Exposure route/period	Case history	Main results	Reference
Pure oil of black cumin	Not specified	Used on the neck for 3 months	28-year-old man for treatment of sore throat	Allergic contact dermatitis	[60]
EO of the seeds of black cumin	Not specified	Repeatedly applied as an ointment	31-year-old woman with an 8-month history of eczema on both hands	Allergic contact dermatitis	[61]
Capsules of BCEO	Containing 500 mg of organic N. sativa oil and 7.5 mg of vitamin E	Daily 15 days	56-year-old woman	Severe bullous target-like lesions, compatible with erythema multiforme	[80]