Nigella sativa (black seed) safety: an overview

Habibeh Mashayekhi-Sardoo; Ramin Rezaee; Gholamreza Karimi

doi:10.1515/abm-2020-0020

Figures & Tables

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).

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/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]
N. sativa AE 2, 6.4, 21, 33, and 60 g/kg, orally), p.o	mice	6 weeks	Same 6 weeks	21 g/kg: hepatotoxic 60 g/kg: high mortality	[65]
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]

Nigella sativa (black seed) safety: an overview

Figures & Tables

Figure 1

Figure 2

Subacute toxicity of Nigella sativa in animal studies

Cytotoxic and genotoxic properties of Nigella sativa in vitro

Acute toxicity of Nigella sativa in animal studies

Subchronic toxicity of Nigella sativa in animal studies

Chronic toxicity of Nigella sativa in animal studies

Nigella sativa toxicity in humans

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