Nigella Sativa

Author: giulia nicolaci
Date: 03/06/2014


Giulia Nicolaci
Regge Gianas Nicolò


Nigella sativa is an annual flowering plant, native to south and southwest Asia. It grows to 20–30 cm tall, with finely divided, linear leaves. The flowers are delicate, and usually coloured pale blue and white, with five to ten petals. The fruit is a large and inflated capsule composed of three to seven united follicles, each containing numerous seeds. The seed is used as a spice.
In English, Nigella sativa seed is variously called, among the most used names are black cumin and blackseed because of the dark colour of the seeds.
Archaeological evidence about the earliest cultivation of N. sativa have been found in several sites from ancient Egypt, including Tutankhamun's tomb.


Most of the therapeutic properties of this plant are due to the presence of thymoquinone (TQ) which is the major bioactive component of the essential oil (30%-48%). Other important active compounds are: thymohydroquinone, dithymoquinone, nigellone, p-cymene, carvacrol, 4-terpineol, t-anethol; moreover, isoquinoline and pyrazol alkaloids, alpha-hederin, carvone, limonene, citronella can be found in the seeds.
Nigella sativa: A miracle herb. 2013
Metabocard of TQ


Order: Ranunculales
Family: Ranunculaceae
Genus: Nigella
Species: N. sativa


Extensive studies on N. sativa have been carried out by various researchers and a wide spectrum of its pharmacological actions have been explored which may include: antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, anti-inflammatory, bronchodilator, hepato-protective, reno-protective, gastro-protective, antioxidant properties, etc. Due to its miraculous power of healing, N. sativa has got the place among the top ranked evidence based herbal medicines.
Nigella sativa: A miracle herb. 2013


Antibiotic activity

TQ exhibited a significant bactericidal activity against various human pathogenic bacteria especially Gram positive cocci preventing cell adhesion to glass slides surface.
N. sativa also have a strong antifungal effect against different strains of Candida albicans and Antidermatophyte, supporting its use in folk medicine for the treatment of fungal skin infections.
Two novel antifungal defensins, named Ns-D1 and Ns-D2, were isolated from the seeds; their high antifungal activity makes them promising candidates for engineering pathogen-resistant plants.
Nigella sativa: A miracle herb. 2013

Results of in vitro testing of N. sativa seeds against Schistosoma mansoni, miracidia, cercariae, and adult worms indicate its strong biocidal effects, comparable to those of piperazine, against all stages of the parasite. This was related to its ability of inducing an oxidative stress which could in turn render the parasite vulnerable to damage by the host.
Pharmacological and toxicological properties of Nigella sativa. 2003


Biochemical and ultrastructural findings suggest that N. sativa extract and TQ have therapeutic effects against diabetes comparable to metformin. The hypoglycemic effect observed were due to amelioration of β-cell ultrastructure through decreased oxidative stress, increased insulin secretion and reduced sodium-dependent glucose transport across jejunum.
Nigella sativa seed extracts enhance glucose-induced insulin release from rat-isolated Langerhans islets. 2004
Nigella sativa inhibits intestinal glucose absorption and improves glucose tolerance in rats. 2009

Western blot analysis showed increased levels of MAPK p42/44erk as well as PKB/Akt. The MAPK p44/42erk is well known to be stimulated by insulin and to participate in the stimulation of cell proliferation and protein synthesis. On the other hand, PKB/Akt is a kinase that lies downstream of PI3K, enhancing glucose transport in skeletal muscle.
The results indicate that black seed might be a beneficial adjuvant to oral hypoglycemic agents in type 2 diabetic patients.
The petroleum ether extract of Nigella sativa exerts lipid-lowering and insulin-sensitizing actions in the rat. 2004
Effect of Nigella sativa seeds on the glycemic control of patients with type 2 diabetes mellitus. 2010


N. sativa oil dose-dependently decreases arterial blood pressure and heart rate. Part of these effetcs is mediated centrally via direct and indirect interaction with tryptaminergic and cholinergic systems. N. sativa seeds are also endowed with strong diuretic action with increased excretion of chloride, sodium, potassium and urea. Main pressure reduction was 22%, compared with that of the calcium channel blocker nifedipine which caused an 18% decrease in arterial blood pressure.
Pharmacological and toxicological properties of Nigella sativa. 2003

N. sativa oil showed inhibitory effects on arachidonic acid induced platelet aggregation and blood coagulation more potent than aspirin.
Moreover, studies showed that the extract of Nigella sativa significantly reduced plasma triglycerides while increasing HDL-cholesterol via a reduction in HMG-CoA reductase activity, and an increase in arylesterase activity. The compounds also blocked the production of highly atherogenic sd-LDL thus reducing cardiovascular risk.
The petroleum ether extract of Nigella sativa exerts lipid-lowering and insulin-sensitizing actions in the rat. 2004

Nervous System

N. sativa increases 5-HT and GABA levels in rats brain improving learning and producing anxiolytic effects.
It has also been reported a strong analgesic effect through indirect activation of the superspinal μ1 and κ receptors.
Some results indicate that the potent antioxidant effects of NSO reduce excitability and induction of seizures in epileptic animals and improve some of the adverse effects of antiepileptic drugs.
Nigella sativa: A miracle herb. 2013

Respiratory System

N. sativa has spasmolytic and bronchodilator actions; possible mechanisms for these effects are: stimulation of β-adrenegic receptors, stimulation of inhibitory non-adrenergic non-cholinergic nervous system (NANC) or inhibition of stimulatory NANC, methylxanthine activity, inhibition of phosphodiesterase and calcium channel, modulation of potassium channels. The active compound seems to be Nigellone whilst TQ do not have such effects.
Possible mechanism(s) for relaxant effect of aqueous and macerated extracts from Nigella sativa on tracheal chains of guinea pig. 2004
Pharmacological and toxicological properties of Nigella sativa. 2003

N. sativa treatment also inhibits inflammatory pulmonary responses, reducing significantly peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar macrophages, interstitial fibrosis, granuloma and necrosis formation. This significantly improved asma symptoms severity and frequency, together with PFT values.
The possible prophylactic effect of Nigella sativa seed extract in asthmatic patients. 2007

Gastroenteric Protection

TQ, especially the high dose level, corrected ischemia/reperfusion stomach insult in a comparable manner to that of the reference drug used, omeprazole. Besides the antioxidant property, TQ inhibits proton pump, pepsin secretion and neutrophil infiltration, while enhancing mucin secretion, prostaglandine activity and nitric oxide production.
Antibacterial activity of N. sativa against Helicobacter Pylori in patients with non-ulcer dyspepsia is comparable to standard triple therapy.

The mechanism of the hepatoprotective action of thymoquinone is not certain, but may be related to the preservation of intracellular glutathione, inhibition of thromboxane B2 production and lipid peroxidation. TQ also attenuates liver fibrosis partially via blocking TLR4 and CD14 expression and PI3K/AKT phosphorylation.
Nigella sativa: A miracle herb. 2013
Pharmacological and toxicological properties of Nigella sativa. 2003

Antioxidant Activity

Compounds isolated from N. sativa (including thymoquinone, carvacol, t-anethole and 4-terpineol) have appreciable free radical scavenging properties and have been shown to inhibit non-enzymatic lipid peroxidation in liposomes.
Pharmacological and toxicological properties of Nigella sativa. 2003

Many studies showed that N. sativa increases the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx) etc; moreover, topical application, induced heme oxygenase-1, NADH-quinoneoxidoreductase-1, glutathione-S-transferase and glutamate cysteine ligase in mouse skin.
Inhibition of 5-lipoxygenase and leukotriene C4 synthase in human blood cells by thymoquinone. 2004

Due to its antioxidant activity, N. sativa oil has nephroprotective effect as it lowers the values of serum creatinine and blood urea nitrogen compared to control.
Pharmacological and toxicological properties of Nigella sativa. 2003


TQ diminished nuclear translocation and DNA binding of nuclear factor-kappaB (NF-κB), attenuates the phosphorylation of Akt, c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase.
Together with its ability to induce the expression of cytoprotective proteins, this provides a mechanistic basis of anti-inflammatory and antioxidative effects of TQ.
Oral administration resulted in significantly reduced levels of pro-inflammatory mediators [IL-1β, IL-6, TNF-α, IFN-γ and PGE~2~], increase in IL-10, attenuate expression of cyclooxygenase-2 (preventing eicosanoid generation) and inhibits HDAC activity.

In addition N. sativa favors the secretion of Th2, versus Th1, cytokines by splenocytes and enhances NK cytotoxic activity.
These effects were tested on experimental autoimmune encephalomyelitis (EAE), an animal model that mimic human multiple sclerosis. TQ was found to be almost 90% preventive and 50% curative in chronic relapsing EAE due to its antioxidant and immunomodulating effects.
Pharmacological and toxicological properties of Nigella sativa. 2003


Many studies have been carried out on Nigella and its activity against cancers. First of all, studies found that TQ suppressed TNF-induced NF-kappa B activation in a dose- and time-dependent manner. This is correlated with sequential inhibition of IKK (IkB kinase), IkB phosphorylation and degradation, p65 nuclear translocation.

Studies on myeloblastic leukemia shows that TQ -induced apoptosis is associated with upregulation of Bax, downregulation of Bcl2 proteins and activation of caspases 3, 9 and 8; these effect on Bcl2 is linked to and dependent on p53.
TQ also down-regulates the expression of NF-kappa B antiapoptotic gene products (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, and survivin). Finally, it specifically repressed PDE1A expression in acute lymphoblastic leukemia thus modulating cAMP and cGMP-dependent cell death pathways.
Anticancer activities of Nigella saliva. 2011

Studies on APC- mice fed with TQ have obtained the following results: decreased number of large polyps in small intestine and induced apoptosis in neoplastic tissue but not in normal mucosa. The expression of B-catenin, c-myc and Ki-67 was evaluated with immunohistochemistry: β-catenin was retained at the membrane and c-myc decreased in nucleus; in vitro it has been shown that TQ induce these effects through GSK-3β activation.
Thymoquinone attenuates tumor growth in ApcMin mice by interference with Wnt-signaling. 2013

Researchers found that TQ inhibits DNA synthesis, proliferation, and viability of cancerous prostate epithelial cells by down-regulating AR (androgen receptor) and E2F-1 (a transcription factor ); it prevents tumor angiogenesis in xenograft human prostate cancer (PC3) models, and inhibits human prostate tumor growth at low dosage with almost no chemotoxic side effects.
TQ also inhibits VEGF-induced extracellular signal-regulated kinase activation but showed no inhibitory effects on VEGFR2 activation.
Anticancer activities of Nigella sativa. 2011

Other studies inquired the anticancer effects of TQ on breast cancer cells, and its potential effect on the PPAR-γ activation pathway . It was found that, apart from the activation of caspases 8, 9 and 7 and the downregulation of Bcl-2, Bcl-xL and survivin , TQ reduces migration and invasive properties of cancer cells. Interestingly, TQ was found to increase PPAR-γ activity: this increase was prevented in presence of PPAR-γ specific inhibitor and PPAR-γ dominant negative plasmid, suggesting that TQ may act as a ligand of PPAR-γ.
Anticancer activity of thymoquinone in breast cancer cells: possible involvement of PPAR-γ pathway. 2011

The effects of thymoquinone on human gene expression has been investigated using DNA microarray technology: analysis revealed a downregulated expression of CYP1A1 and UGT1A8 (by 43- and 11fold, respectively), genes involved in the estrogen metabolic pathway. Moreover, member genes in the INF pathway, reported to be involved in the development of chemoresistance, were reduced.
Finally, other studies revealed a mitochondrial dysfunction in TQ treated cells, by examining the phosphorylation status of PDK1, PTEN, Akt, c-raf, GSK-3β and Bad. After 24h incubation with TQ, cells showed a G1 phase arrest and then the shift to subG1 phase, indicating apoptosis, supported by suppression of cyclin D1, cyclin E and cyclin dependent kinase inhibitor p27 expression.
Molecular targeting of Akt by thymoquinone promotes G(1) arrest through translation inhibition of cyclin D1 and induces apoptosis in breast cancer cells. 2013

The inhibition of migration of melanoma cells by thymoquinone was accompanied by a decreased expression of NLRP3 (constitutively activated in tumor cells) , partly due to ROS reduction, which resulted in inactivation of caspase-1 and in the consequent secretion of IL-1β and IL-18. Thus, the results indicate that thymoquinone can be a potential immunotherapeutic agent not only as an adjuvant therapy for melanoma, but also, in the control and prevention of metastatic melanoma.
Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome. 2013

In addition to these cancer inhibiting properties, components of N. sativa have protective roles, suppressing the negative effect of CCl4 on reported CYP (drug-metabolizing cytochrome P450 enzymes) and protecting against ionizing radiation-related tissue injury (reduction in hemolysin antibodies, leukopenia, decrease in plasma total protein and globulin concentration, depletion of lymphoid follicles of spleen and thymus gland, decrease in GPx, CAT and SOD activities).
Using cervical squamous carcinoma cells the citotoxicity of TQ was compared to cisplatin: TQ was found more ciytotoxic towards tumor cells, but the toxicity was less towards the normal cells.
Nigella sativa: A miracle herb. 2013


In vitro and vivo studies have shown that N. sativa extracts enhanced amoxicillin avaiability inhibiting CYP-450 3A4, 2C9, 3A5 and 3A7. There is a posibility that Nigella may interact with other co-administrated drugs, modulating their pharmacological effect.


No toxic effects were reported when N. sativa fixed oil was given to mice per os both in acute and chronic studies: no changes in key hepatic enzyme levels (AST,ALT,GGT) and normal histopathological results from heart, liver, kidneys and pancreas tissue samples. The low toxicity of N. sativa fixed oil suggests a wide margin of safety for therapeutic use.
Nigella sativa: A miracle herb. 2013

"Use the Black Seed for indeed, it is a cure for all diseases except death."

Prophet Muhammad - Saheeh al-Bukharee 7:591

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