Immunotherapy can take 3 years to desensitize to allergens

Sublingual immunotherapyImmunotherapy can induce tolerance for allergens, but what is a realistic time frame? A study recently published in JAMA demonstrates that 3 years of sublingual desensitizing treatment is effective, but 2 years is no different than placebo. This research helps practitioners working in the larger context of immune plasticity, and patients, to consider pragmatic parameters for case management. The authors note:

“Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment.”

But since reducing the inconvenience and expense of treatment is always desirable, the they set out to…

“…assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up.”

3 years of immunotherapy effective, 2 years comparable to placebo

In a randomized double-blind, placebo-controlled, 3–parallel-group study of adult patients with moderate to allergic rhinitis that was severe enough to interfere with normal daily activities and sleep), thirty-six subjects received 2 years of sublingual immunotherapy (SLIT; daily tablets containing 15 µg of a major allergen and monthly placebo injections), another 36 received subcutaneous immunotherapy (SCIT; monthly injections containing 20 µg of the allergen and daily placebo tablets); and 34 received double placebo. The nasal allergen challenge was performed before and at 1 and 2 years during treatment; and at 3 years, which was1 year after treatment concluded. Their data make clear that, while the effectiveness of 3 years of treatment is well established, 2 years of treatment did essentially nothing.

“Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score [total nasal symptom score] for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5.48) at 3 years, and for the placebo group, the score was 6.06 (95% CI, 5.23 to 6.88) at pretreatment and 4.81 (95% CI, 3.97 to 5.65) at 3 years. The between-group difference (adjusted for baseline) was −0.18 (95% CI, −1.25 to 0.90; [P = .75]).”

In other words, there were no significant differences between the placebo group and the treatment groups, or between the two treatment groups, despite the finding that SCIT appeared to be more effective than SLIT at reducing TNSS after 1 year.

Medscape Family Medicine quotes an editorial by Linda S. Cox, MD:

“…the cumulative costs of symptomatic drug treatment for perennial or seasonal allergic rhinitis can be significant over time,” because it is a chronic condition. Therefore, any analysis of allergen-specific immunotherapy must take into account its potential for long-term disease modification. However, she warns, any cost-benefit assessment of allergen-specific immunotherapy must include “the duration of treatment required for optimal long-term efficacy.” The time commitment requirement may be an important factor in patients’ decisions to initiate therapy.” Therefore, it is important to clarify the optimum duration of treatment. The findings of this study suggest that “2 years is not sufficient for SLIT treatment to induce long-term clinical efficacy.”

Clinical note

This study leaves open the question as to whether adjunctive forms of immunomodulation can accelerate sustained benefit or improve outcomes in other ways, but it does offer one reference by which clinicians and patients can appreciate the dynamic and time frame of therapies addressing immune and neuroplasticity.

The authors conclude:

“Among patients with moderate to severe seasonal allergic rhinitis, 2 years of sublingual grass pollen immunotherapy was not significantly different from placebo in improving the nasal response to allergen challenge at 3-year follow-up.”

Nigella sativa, a true ‘wonder medicine’?

Nigella sativa flower and seedsNigella sativa, also known as black cumin, produces seeds with a mind-boggling wealth of medicinal virtues. For colleagues and others who may not be familiar with the abundance of scientific evidence for the use of Nigella sativa seed extract in clinical practice, this selection of citations serves as an introduction to its wide range of indications.

An illustrious history

Asian Pacific Journal of Tropical MedicineTraditional uses of Nigella sativa are surveyed in a paper published in the Asian Pacific Journal of Tropical Medicine:

Nigella sativa (N. sativa) (Family Ranunculaceae) is a widely used medicinal plant throughout the world. It is very popular in various traditional systems of medicine like Unani and Tibb, Ayurveda and Siddha. Seeds and oil have a long history of folklore usage in various systems of medicines and food. The seeds of N. sativa have been widely used in the treatment of different diseases and ailments. In Islamic literature, it is considered as one of the greatest forms of healing medicine. It has been recommended for using on regular basis in Tibb-e-Nabwi (Prophetic Medicine). It has been widely used as antihypertensive, liver tonics, diuretics, digestive, anti-diarrheal, appetite stimulant, analgesics, anti-bacterial and in skin disorders. 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, spasmolytic, bronchodilator, hepato-protective, renal 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. This is also revealed that most of the therapeutic properties of this plant are due to the presence of thymoquinone which is major bioactive component of the essential oil. The present review is an effort to provide a detailed survey of the literature on scientific researches of pharmacognostical characteristics, chemical composition and pharmacological activities of the seeds of this plant.”

Critical Reviews in Food Science and NutritionA paper published in the journal Critical Reviews in Food Science and Nutrition also suggests Nigella sativa’s wide scope of use:

“…It possesses a nutritional dense profile as its fixed oil (lipid fraction), is rich in unsaturated fatty acids while essential oil contains thymoquinone and carvacrol as antioxidants. N. sativa seeds also contain proteins, alkaloids (nigellicines and nigelledine), and saponins (α-hederin) in substantial amounts. Recent pharmacological investigations suggested its potential role, especially for the amelioration of oxidative stress through free radical scavenging activity, the induction of apoptosis to cure various cancer lines, the reduction of blood glucose, and the prevention of complications from diabetes. It regulates hematological and serological aspects and can be effective in dyslipidemia and respiratory disorders. Moreover, its immunopotentiating and immunomodulating role brings balance in the immune system. Evidence is available supporting the utilization of Nigella sativa and its bioactive components in a daily diet for health improvement. This review is intended to focus on the composition of Nigella sativa and to elaborate its possible therapeutic roles as a functional food to prevent an array of maladies.”

Anti-inflammatory activity

Molecular Biology ReportsChronic inflammation is a hallmark of most chronic degenerative diseases. A study published in Molecular Biology Reports demonstrates that Nigella sativa reduces inflammation triggered by LPS (lipopolysaccharide), of particular relevance for autoimmunity.

“Inflammation has an important role in many diseases such as cystic fibrosis, allergies and cancer. The free radicals produced during inflammation, can induce gene mutations and posttranslational modifications of cancer related proteins. Nigella sativa L. (N. sativa) is herbaceous plant and commonly used as a natural food. It has many pharmacological effects including antibacterial, antifungal, antitumor, analgesic, antipyretic activity. The aim of this study was to investigate the anti-inflammatuar and anti-oxidant activity of N. sativa in acute inflammation. Thus we used the experimental lipopolysaccharides (LPS)-induced model. Intraperitoneal LPS 1 mg/kg was administered to groups. N. sativa (500 mg/kg) and essential oil (5 ml/kg) were given orally to treatment groups, after 24-h of intraperitoneal LPS-injection. To determine the lung inflammation, 18F-fluoro-deoxy-d-glucose (0.8 ml/kg) was administrated under the anesthesia before the 1 h of PET-scanning. After the FDG-PET, samples were collected. Lung and liver18F-FDG-uptake was calculated. Serum AST, ALT, LDH and hcCRP levels were determined and liver, lung and erythrocyte SOD, MDA and CAT levels were measured. Liver and lung NO and DNA fragmentation levels were determined. MDA levels were decreased in treated inflammation groups whereas increased in untreated inflammation group. SOD and CAT activities in untreated inflammation group were significantly lower. According to the control group, increased AST and ALT levels were found in untreated inflammation group. 18F-FDG uptake of inflammation groups were increased when compare the control group… We conclude that, in LPS-induced inflammation, N. sativa have therapeutic and anti-oxidant effects.”

Immunomodulatory effects of Nigella sativa

Chinese Journal of Integrative MedicineA fascinating study in the Chinese Journal of Integrative Medicine offers evidence that Nigella sativa, beyond having simply an anti-inflammatory effect, is an immunomodulator that may help to restore healthier immune regulation:

“Cells isolated from human PBMCs which were treated with methanolic extract of NS for 48 h into two separate environments (PHA and non-PHA stimulated). Flow cytometry (for T helper/inducer cells and natural killer cells) and real time-polymerase chain reaction (PCR) assays for a few selected proinflammatory gene expressions were performed. Extracts from NS had an immunostimulating effect on non-PHA-stimulated proliferation of human PBMCs. In contrast, immunosuppressive activity was observed on PHA-stimulated proliferation of human PBMCs.”

Antimicrobial activity

BioMed Research InternationalNigella sativa has also shown good effect in the treatment of infections. A study recently published in Biomed Research International validates its antibacterial and antifungal properties:

“…major components in black cumin essential oils which were thymoquinone (37.6%) followed by p-cymene (31.2%), α-thujene (5.6%), thymohydroquinone (3.4%), and longifolene (2.0%), whereas the oleoresins extracted in different solvents contain linoleic acid as a major component….The essential oil showed up to 90% zone inhibition against Fusarium moniliforme in inverted petri plate method. Using agar well diffusion method for evaluating antibacterial activity, the essential oil was found to be highly effective against Gram-positive bacteria.”

The authors summarize their findings by concluding:

“The results obtained in antimicrobial investigations of black cumin oil and oleoresins were in good agreement with the previous reported work…Seeds of black cumin seem to possess magical properties and have been worked out extensively. This study revealed that black cumin essential oil and its oleoresins constitute a good alternative source of essential fatty acids compared with common vegetable oil. The present results showed that essential oil and oleoresins of black cumin exhibited higher antioxidant activity than synthetic antioxidants. These findings could be used to prepare multipurpose products for pharmaceutical applications and its usage as dietary source of antioxidant should be considered largely for alleviating and ameliorating diseases.”

World Journal of GastroenterologyPotent antiviral effects of Nigella sativa are in evidence in a study published in the World Journal of Gastroenterology on hepatitis C:

“Thirty patients with hepatitis C virus (HCV) infection, who were not eligible for IFN/ribavirin therapy, were included in the present study…Various parameters, including clinical parameters, complete blood count, liver function, renal function, plasma glucose, total antioxidant capacity (TAC), and polymerase chain reaction, were all assessed at baseline and at the end of the study. Clinical assessment included: hepato and/or splenomegaly, jaundice, palmar erythema, flapping tremors, spider naevi, lower-limb edema, and ascites. N. sativa was administered for three successive months at a dose of (450 mg three times daily). Clinical response and incidence of adverse drug reactions were assessed initially, periodically, and at the end of the study.”

The improvements noted were outstanding:

“N. sativa administration significantly improved HCV viral load. After N. sativa administration, the following laboratory parameters improved: total protein, albumin, red blood cell count, and platelet count. Fasting blood glucose and postprandial blood glucose were significantly decreased in both diabetic and non-diabetic HCV patients. Patients with lower-limb edema decreased significantly from baseline compared with after treatment. Adverse drug reactions were unremarkable except for a few cases of epigastric pain and hypoglycemia that did not affect patient compliance.”

Clinicians involved in case management of HCV should note their conclusion:

N. sativa administration in patients with HCV was tolerable, safe, decreased viral load, and improved oxidative stress, clinical condition and glycemic control in diabetic patients.”

 Amelioration of metabolic disorders

Plant Foods for Human NutritionNigella sativa possesses remarkable properties that improve metabolic disorders ranging including insulin resistance and diabetes, obesity, and liver fibrosis. From a paper in Plant Foods for Human Nutrition:

“Obesity is closely associated with increased incidence of cardiovascular diseases, cancer, insulin resistance, and immune dysfunction, and thus obesity-mitigation strategies should take into account these secondary pathologies in addition to promoting weight loss. Recent studies indicate that black cumin (Nigella sativa) has cardio-protective, anti-cancer, anti-diabetic, antioxidant, and immune-modulatory properties.”


Evidence-Based Complementary and Alternative MedicineEvidence for its benefit in diabetes is offered in a study published in Evidence-Based Complementary and Alternative Medicine:

“The main objective of this instant study was to explore the antidiabetic potential of Nigella sativa fixed oil (NSFO) and essential oil (NSEO). Three experimental groups of rats received diets during the entire study duration, that is, D1 (control), D2 (NSFO: 4.0%), and D3 (NSEO: 0.30%). Experimental diets (NSFO & NSEO) modulated the lipid profile, while decreasing the antioxidant damage. However, production of free radicals, that is, MDA, and conjugated dienes increased by 59.00 and 33.63%, respectively, in control. On the contrary, NSFO and NSEO reduced the MDA levels by 11.54 and 26.86% and the conjugated dienes levels by 32.53 and 38.39%, respectively. N. sativa oils improved the health and showed some promising anti-diabetic results.”

BMC Complementary & Alternative MedicineAnother study on Nigella sativa and diabetes was recently published in BMC Complementary and Alternative Medicine.

Nigella sativa fixed (NSFO) and essential (NSEO) oils have been used to treat diabetes mellitus and its complications. Present study was undertaken to explore and validate these folkloric uses…Sprague dawley rats having streptozotocin (STZ) induced diabetes mellitus were used to assess the role of NSFO and NSEO in the management of diabetes complications.”

Of note is its ability to increase levels of glutathione:

“The results indicated that STZ decreased the glutathione contents (25.72%), while NSFO and NSEO increased the trait significantly. Experimental diets increased the tocopherol contents and enhanced the expression of hepatic enzymes. Correlation matrix further indicated that antioxidant potential is positively associated responsible for the modulation of hepatic enzymes and the decrease of the nitric oxide production thus controlling the diabetes complications.”

Nigella sativa lowers cholesterol

Advanced Pharmaceutical BulletinCholesterol along with blood glucose was lowered in a study on Nigella sative for metabolic syndrome in menopausal women published in the Advanced Pharmaceutical Bulletin:

“Thirty subjects who were menopausal women within the age limit of 45-60 were participated in this study and randomly allotted into two experimental groups. The treatment group was orally administered with N. sativa seeds powder in the form of capsules at a dose of 1g per day after breakfast for period of two months and compared to control group given placebo…significant improvement was observed in total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and blood glucose…These results suggested that treatment with N. sativa exert a protective effect by improving lipid profile and blood glucose which are in higher risk to be elevated during menopausal period.”

Journal of Translational MedicineImprovements in hypercholesterolemia in menopause were also documented in a study recently published in the Journal of Translational Medicine:

“In this study, Nigella sativa was evaluated for its hypolipidemic effects among menopausal women. In a randomised trial, hyperlipidemic menopausal women were assigned to treatment (n = 19) or placebo groups (n = 18), and given N. sativa or placebo for two months after their informed consents were sought. At baseline, blood samples were taken and at one month intervals thereafter until one month after the end of the study…The results showed that N. sativa significantly improved lipid profiles of menopausal women (decreased total cholesterol, low density lipoprotein cholesterol and triglyceride, and increased high density lipoprotein cholesterol) more than the placebo treatment over 2 months of intervention.”

These benefits persisted for a month after treatment with Nigella sativa was discontinued:

One month after cessation of treatment, the lipid profiles in the N. sativa-treated group tended to change towards the pretreatment levels.”

The authors conclude:

“N. sativa is thought to have multiple mechanisms of action and is cost-effective. Therefore, it could be used by menopausal women to remedy hypercholesterolemia, with likely more benefits than with single pharmacological agents that may cause side effects. The use of N. sativa as an alternative therapy for hypercholesterolemia could have profound impact on the management of CVD among menopausal women especially in countries where it is readily available.”

International Journal of Preventive MedicineAnd a study in the International Journal of Preventive Medicine documented improvements in lipid metabolism and oxygen utilization:

“In this randomized, double-blind, controlled trial…20 sedentary overweight females were divided into two groups and assigned to N. sativa supplementation (N. sativa capsules) or a placebo for the 8 weeks, both groups participated in an aerobic training program (3 times/week)…. Blood lipids and VO2 max were determined at baseline and at the end of 8 weeks…N. sativa supplementation lowered total cholesterol (TC), triglyceride, low-density lipoprotein (LDL) and body mass index and increased high density lipoprotein (HDL) and VO2 max.”

It’s worth noting that the diet of the study subjects remained the same:

Since we asked all subjects not to change their usual daily diet, it seems that this changes may be due to the result of consuming black seeds and regular aerobic training.”

Interestingly in regard to lowering cholesterol:

“The hypotriglyceridemic effect of N. sativa is possibly due to its choleretic activity. The choleretic function of N. sativa is either by reducing the synthesis of cholesterol by hepatocytes or by decreasing its fractional reabsorption from the small intestine.”

Nigella sativa’s thymoquinone ameliorates liver fibrosis

International ImmunopharmacologyWith the proliferation of NAFLD and NASH medicines that sustainably alleviate hepatic fibrosis are in urgent need. A study published in International Immunopharmacology offers evidence that thymoquinone, a principal compound in Nigella sativa, has potent hepatic anti-fibrotic effects:

Thymoquinone (TQ) is the major active compound derived from the medicinal Nigella sativa. In the present study, we investigated the anti-fibrotic mechanism of TQ in lipopolysaccharide (LPS)-activated rat hepatic stellate cells line, T-HSC/Cl-6. T-HSC/Cl-6 cells were treated with TQ (3.125, 6.25 and 12.5 μM) prior to LPS (1 μg/ml). Our data demonstrated that TQ effectively decreased activated T-HSC/Cl-6 cell viability. TQ significantly attenuated the expression of CD14 and Toll-like receptor 4 (TLR4). TQ also significantly inhibited phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase-protein kinase B (Akt) phosphorylation. The expression of α-SMA and collagen-I were significantly decreased by TQ. Furthermore, TQ decreased X linked inhibitor of apoptosis (XIAP) and cellular FLIP (c-FLIPL) expression, which are related with the regulation of apoptosis. Furthermore, TQ significantly increased the survival against LPS challenge in d-galactosamine (d-GlaN)-sensitized mice, and decreased the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which were in line with in vitro results. Our data demonstrated that TQ attenuates liver fibrosis partially via blocking TLR4 expression and PI3K phosphorylation on the activated HSCs. Therefore, TQ may be a potential candidate for the therapy of hepatic fibrosis.

A follow-up study published recently in the same journal added more evidence to Nigella sativa’s benefits for hepatic fibrosis:Hepatic fibrosis attenuated by thymoquinone

“The current study was conducted to investigate the anti-fibrotic effect and its possible underlying mechanisms of thymoquinone (TQ) against hepatic fibrosis in vivo. TQ is the major active compound derived from the medicinal Nigella sativa. Liver fibrosis was induced in male Kunming mice by intraperitoneal injections of thioacetamide (TAA, 200 mg/kg). Mice were treated concurrently with TAA alone or TAA plus TQ (20 mg/kg or 40 mg/kg) given daily by oral gavage. Our data demonstrated that TQ treatment obviously reversed liver tissue damage compared with TAA alone group, characterized by less inflammatory infiltration and accumulation of extracellular matrix (ECM) proteins. TQ significantly attenuated TAA-induced liver fibrosis, accompanied by reduced protein and mRNA expression of α-smooth muscle actin (α-SMA), collagen-І and tissue inhibitor of metalloproteinase-1 (TIMP-1). TQ downregulated the expression of toll-like receptor 4 (TLR4) and remarkably decreased proinflammatory cytokine levels as well. TQ also significantly inhibited phosphatidylinositol 3-kinase (PI3K) phosphorylation. Furthermore, TQ enhanced the phosphorylation adenosine monophosphate-activated protein kinase (AMPK) and liver kinase B (LKB)-1. In conclusion, TQ may reduce ECM accumulation, and it may be at least regulated by phosphorylation of AMPK signaling pathways, suggesting that TQ may be a potential candidate for the therapy of hepatic fibrosis.

 Protection against diabetic kidney damage

Ultrastructural PathologyThymoquinone in Nigella sativa also reduced experimentally induced kidney damage in models of diabetes as reported in a study published in Ultrastructural Pathology:

“Diabetic rats exhibited morphological changes in both renal glomeruli and tubules with immunohistochemical expression of the mesenchymal markers Fsp1, desmin, and MMP-17 and disappearance of the epithelial marker ZO-1 largely in the glomeruli of diabetic kidneys. Treatment with TQ significantly attenuated renal morphological and immunohistochemical changes in STZ-induced diabetic ratsThymoquinone has protective effects on experimental diabetic nephropathy. Both mesenchymal and epithelial markers serve as excellent predictors of early kidney damage and indicators of TQ responsiveness in STZ-induced diabetic nephropathy.”

Hypertension and Oxidative Stress

Regarding the anti-hypertensive effects of Nigella sativa, from a paperEvidence-Based Complementary and Alternative Medicine in Evidence-Based Complementary & Alternative Medicine:

Excessive production of reactive oxygen species reduces nitric oxide bioavailability leading to an endothelial dysfunction and a subsequent increase in total peripheral resistance…Nigella sativa (NS) and its active constituents have been documented to exhibit antioxidant, hypotensive, calcium channel blockade and diuretic properties which may contribute to reduce blood pressure. This suggests a potential role of NS in the management of hypertension…”

Protection Against Heart Damage

Pakistan Journal of Pharmaceutical SciencesNot surprisingly, thymoquinone in Nigella sativa appears to exert protective effects against heart damage associated with coronary insufficiency and stress as documented by a study in the Pakistan Journal of Pharmaceutical Sciences. Here again the beneficial effects include support for glutathione:

“Myocardial injury constitutes a major cause of morbidity and mortality in humans. Present study aimed to investigate protective role of thymoquinone, which is an active principle of Nigella sativa (N. sativa) seed (Commonly called as black seed), in isoproterenol induced myocardial injury, a classical example of excess catecholamines related coronary insufficiency and stress cardiomyopathy. Thymoquinone, in olive oil, was administered orally (12.5, 25 and 50mg/kg) to three groups of Wistar albino rats for 7 days, while two control groups were given plain olive oil. Thereafter, thymoquinone receiving groups and one control group were injected, subcutaneously, with isoproterenol (125mg/kg) for 2 days. Myocardial injury was assessed by biochemical markers (plasma LDH, TBARS, GR & SOD and myocardial GSH/GSSG ratio) and cardiac histopathology. Plasma LDH, TBARS and GR increased in control groups receiving isoproterenol, while there was a dose related decrease in these markers in thymoquinone treated groups, down to levels in controls given olive oil only. Decrease in plasma SOD and myocardial GSH/GSSG ratio and histological changes produced with isoproternol were also reversed in thymoquinone treated rats. Results of our study revealed that thymoquinone protects the heart from injury induced by isoproterenol.”

Anti-cancer effects of Nigella sativa

Drug Discovery TodayThere is a wealth of evidence supporting the use Nigella sativa and its active compound thymoquinone as an adjunctive treatment in numerous malignancies as noted in a paper published earlier this year in Drug Discovery Today:

“Thymoquinone (TQ), the main active constituent of black seed essential oil, exhibits promising effects against inflammatory diseases and cancer. TQ, modulates signaling pathways that are key to cancer progression, and enhances the anticancer potential of clinical drugs while reducing their toxic side effects. Considering that TQ was isolated 50 years ago, this review focuses on TQ’s chemical and pharmacological properties and the latest advances in TQ analog design and nanoformulation. We discuss our current state of knowledge of TQ’s adjuvant potential and in vivo antitumor activity and highlight its ability to modulate the hallmarks of cancer.

  • This year marks 50 years since thymoquinone was isolated from black seed.
  • Thymoquinone has had a long history of battling cancer in vitro and in vivo.
  • Thymoquinone modulates nine of the ten hallmarks of cancer.”

American Journal of Chinese MedicineA paper in the American Journal of Chinese Medicine reviews Nigella sativa’s anticancer activities:

“…quite a few pharmacological effects of N. sativa seed, its oil, various extracts and active components have been identified to include immune stimulation, anti-inflammation, hypoglycemic, antihypertensive, antiasthmatic, antimicrobial, antiparasitic, antioxidant and anticancer effects…A literature search has revealed that a lot more studies have been recently carried out related to the anticancer activities of N. sativa and some of its active compounds, such as thymoquinone and alpha-hederin. Acute and chronic toxicity studies have recently confirmed the safety of N. sativa oil and its most abundant active component, thymoquinone, particularly when given orally. The present work is aimed at summarizing the extremely valuable work done by various investigators on the effects of N. sativa seed, its extracts and active principles against cancer. Those related to the underlying mechanism of action, derivatives of thymoquinone, nano thymoquinone and combinations of thymoquinone with the currently used cytotoxic drugs are of particular interest.”

Thymoquinone mechanisms of actionA paper in the African Journal of Traditional, Complementary and Alternative Medicines describes its activity against a number of malignancies and the molecular mechanisms involved:

“Nigella sativa has been used as traditional medicine for centuries. The crude oil and thymoquinone (TQ) extracted from its seeds and oil are effective against many diseases like cancer, cardiovascular complications, diabetes, asthma, kidney disease etc. It is effective against cancer in blood system, lung, kidney, liver, prostate, breast, cervix, skin with much safety. The molecular mechanisms behind its anticancer role is still not clearly understood, however, some studies showed that TQ has antioxidant role and improves body’s defense system, induces apoptosis and controls Akt pathway. Although the anti-cancer activity of N. sativa components was recognized thousands of years ago but proper scientific research with this important traditional medicine is a history of last 2∼3 decades…In this article, we have summarized the actions of TQ and crude oil of N. sativa against different cancers with their molecular mechanisms.”

Pharmacognosy ReviewsA review article in Pharmacognosy Review notes the anti-cancer potential implied by numerous investigations:

“Thymoquinone (TQ) is the bioactive phytochemical constituent of the seeds oil of Nigella sativa. In vitro and in vivo research has thoroughly investigated the anticancer effects of TQ against several cancer cell lines and animal models. As a result, a considerable amount of information has been generated from research thus providing a better understanding of the anti-proliferating activity of this compound. Therefore, it is appropriate that TQ should move from testing on the bench to clinical experiments. The purpose of this review is to highlight the potential of TQ as an anticancer agent and the chances of this compound in the clinical treatment of cancer, with special attention on breast cancer treatment.”

Evidence-Based Complementary and Alternative MedicineA paper in Evidence-Based Complementary and Alternative Medicine outlines mechanisms by which thymoquinone in Nigella sativa can act to prevent cancer:

Earlier studies have shown that N. sativa and its constituent thymoquinone (TQ) have important roles in the prevention and treatment of cancer by modulating cell signaling pathways. In this review, we summarize the role of N. sativa and its constituents TQ in the prevention of cancer through the activation or inactivation of molecular cell signaling pathways.”

Upregulation of tumor suppressor gene and inhibition of VEGF, Akt/PI3K pathways:

Upregulation of tumor suppresor geneThymoquinone role in prevention of cancer via modulation of phase I and phase II enzymes:

Thymoquinone's role in cancer prevention

Osteosarcoma, angiogenesis and NF-κB

Oncology ReportsEvidence for thymoquinone’s benefit in osteosarcoma through inhibition of tumor angiogenesis and tumor growth by suppressing NF-κB is offered by a study published in Oncology Reports:

“Recent studies reported that thymoquinone exhibited inhibitory effects on the cell proliferation of several cancer cell lines. This study was performed to investigate the antitumor and anti-angiogenic effects of thymoquinone on osteosarcoma in vitro and in vivo. Our results showed that thymoquinone induced a higher percentage of growth inhibition and apoptosis in the human osteosarcoma cell line SaOS-2 compared to that of control, and thymoquinone significantly blocked human umbilical vein endothelial cell (HUVEC) tube formation in a dose-dependent manner. To investigate the possible mechanisms involved in these events, we performed electrophoretic mobility shift assay (EMSA) and western blot analysis, and found that thymoquinone significantly downregulated NF-κB DNA-binding activity, XIAP, survivin and VEGF in SaOS-2 cells. Moreover, the expression of cleaved caspase-3 and Smac were upregulated in SaOS-2 cells after treatment with thymoquinone. In addition to these in vitro results, we also found that thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing NF-κB and its regulated molecules. Collectively, our results demonstrate that thymoquinone effectively inhibits tumor growth and angiogenesis both in vitro and in vivo. Moreover, inhibition of NF-κB and downstream effector molecules is a possible underlying mechanism of the antitumor and anti-angiogenic activity of thymoquinone in osteosarcoma.”

Cytotoxic prooxidant effects of thymoquinone in copper rich malignant tissues

Cell Death & DiseaseUsing prostate cancer cells, a fascinating study published in Cell Death & Disease demonstrates that thymoquinone has a beneficial prooxidant cytoxic effect in copper-rich malignant tissue:

“Thymoquinone (TQ) is the major bioactive constituent of volatile oil of Nigella sativa and has been shown to exert various pharmacological properties, such as anti-inflammatory, cardiovascular, analgesic, anti-neoplastic, anticancer and chemopreventive…TQ is a known antioxidant at lower concentrations and most of the studies elucidating the mechanism have centered on the antioxidant property. However, recent publications have shown that TQ may act as a prooxidant at higher Nigella sativa flower 2concentrations. It is well known that plant-derived antioxidants can switch to prooxidants even at low concentrations in the presence of transition metal ions such as copper. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Copper is an important metal ion present in the chromatin and is closely associated with DNA bases, particularly guanine. Using human peripheral lymphocytes and comet assay, we first show that TQ is able to cause oxidative cellular DNA breakage. Such a DNA breakage can be inhibited by copper-chelating agents, neocuproine and bathocuproine, and scavengers of reactive oxygen species. Further, it is seen that TQ targets cellular copper in prostate cancer cell lines leading to a prooxidant cell death.”


“We believe that such a prooxidant cytotoxic mechanism better explains the anticancer activity of plant-derived antioxidants.”

Inhibition of cell proliferation in liver cancer

Toxicology LettersMarked inhibition of tumor multiplicity in hepatocellular carcinoma was shown in a study published in Toxicology Letters:

“…agents that inhibit cell proliferation and restrain hepatic tumorigenesis through cell cycle regulation have a beneficial effect in the treatment of hepatocellular carcinogenesis. The present study was aimed to investigate the efficacy of thymoquinone (TQ), an active compound derived from the medicinal plant Nigella sativa, on N-nitrosodiethylamine (NDEA) [0.01% in drinking water for 16 weeks]-induced hepatocarcinogenesis in experimental rats. After experimental period, the hepatic nodules, liver injury markers and tumor markers levels were substantially increased in NDEA induced liver tumors in rats. However, TQ (20 mg/kg body weight) treatment greatly reduced liver injury markers and decreased tumor markers and prevented hepatic nodule formation and reduced tumor multiplicity in NDEA induced hepatic cancer bearing rats and this was evident from argyrophilic nucleolar organizer region (AgNORs) staining. Moreover…TQ significantly reduced the detrimental alterations by abrogating cell proliferation, which strongly induced G1/S arrest in cell cycle transition. In conclusion, our results suggest that TQ has a potent anti proliferative activity by regulating the G1/S phase cell cycle transition and exhibits a beneficial role in the treatment of HCC.”

Thymoquinone induces glioblastoma cell death

PLOS ONEA fascinating study in PLoS One demonstrates that thymoquinone is a rare agent that can inhibit autophagy (the cellular ‘housecleaning’ process by which degraded cellular components are removed) to promote malignant cell death in the brain cancer gliosblastoma:

“Glioblastoma is the most aggressive and common type of malignant brain tumor in humans, with a median survival of 15 months. There is a great need for more therapies for the treatment of glioblastoma…TQ has anti-oxidant, anti-inflammatory and anti-neoplastic actions with selective cytotoxicity for human cancer cells compared to normal cells. Here, we show that TQ selectively inhibits the clonogenicity of glioblastoma cells as compared to normal human astrocytes. Also, glioblastoma cell proliferation could be impaired by chloroquine, an autophagy inhibitor, suggesting that glioblastoma cells may be dependent on the autophagic pathway for survival…TQ also caused an accumulation of the LC3-associated protein p62, confirming the inhibition of autophagy. Furthermore, the levels of Beclin-1 protein expression were unchanged, indicating that TQ interferes with a later stage of autophagy. Finally, treatment with TQ induces lysosome membrane permeabilization…which mediates caspase-independent cell death… TQ induced apoptosis…”

Inhibition of autophagy by thymoquinoneThe authors note an important difference between the action of thymoquinone and other cytotoxic therapies:

Ionizing radiation and temozolomide have both been shown to increase a cytoprotective autophagy response in glioblastoma cells, leading to resistant tumors. In addition, many other chemotherapeutics, such as rapamycin, tamoxifen, and etoposide, induce a protective autophagic response in cancer cells. Therefore, inhibitors of autophagy, both alone and in combination with standard therapies, may provide a viable and promising new strategy in cancer treatment…To the best of our knowledge, this report represents the first finding of TQ as an autophagy inhibitor, and provides a platform for which to extend studies in the treatment of glioblastoma with TQ.”

The authors conclude:

“Inhibition of autophagy is an exciting and emerging strategy in cancer therapy. In this vein, our results describe a novel mechanism of action for TQ as an autophagy inhibitor selectively targeting glioblastoma cells.

Nigella sativa induces apoptosis in cervical cancer

Natural Product CommunicationsAccording to a study published in Natural Product Communications, Nigella sativa inhibits proliferation of cervical cancer cells by inducing apoptosis:

“Nigella sativa (NS) showed an 88.3% inhibition of proliferation of SiHa human cervical cancer cells at a concentration of 125 microL/mL methanolic extract at 24 h, and an IC50 value 93.2 microL/mL. NS exposure increased the expression of caspase-3, -8 and -9 several-fold. The analysis of apoptosis by Dead End terminal transferase-mediated dUTP-digoxigenin end labeling (TUNEL) assay was used to further confirm that NS induced apoptosis. Thus, NS was concluded to induce apoptosis in SiHa cell through both p53 and caspases activation. NS could potentially be an alternative source of medicine for cervical cancer therapy.”

Suppression of melanoma metastasis by inhibition of the NLRP3 inflammasome

Toxicology and Applied PharmacologyIn an exciting study published in Toxicology and Applied Pharmacology that has implications for a wide range of conditions, investigators report suppression of metastasis in melanoma inhibiting the proinflammatory activity of the NLRP3 inflammasome:

“The inflammasome is a multi-protein complex which when activated regulates caspase-1 activation and IL-1β and IL-18 secretion. The NLRP3 (NACHT, LRR, and pyrin domain-containing protein 3) inflammasome is constitutively assembled and activated in human melanoma cells. We have examined the inhibitory effect of thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone), a major ingredient of black seed obtained from the plant Nigella sativa on metastatic human (A375) and mouse (B16F10) melanoma cell lines. We have assessed whether thymoquinone inhibits metastasis of melanoma cells by targeting NLRP3 subunit of inflammasomes. Using an in vitro cell migration assay, we found that thymoquinone inhibited the migration of both human and mouse melanoma cells…The inhibition of migration of melanoma cells by thymoquinone was accompanied by a decrease in expression of NLRP3 inflammasome resulting in decrease in proteolytic cleavage of caspase-1. Inactivation of caspase-1 by thymoquinone resulted in inhibition of IL-1β and IL-18. Treatment of mouse melanoma cells with thymoquinone also inhibited NF-κB activity. Furthermore, inhibition of reactive oxygen species (ROS) by thymoquinone resulted in partial inactivation of NLRP3 inflammasome. Thus, thymoquinone exerts its inhibitory effect on migration of human and mouse melanoma cells by inhibition of NLRP3 inflammasome. Thus, our 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.”

Readers will recall that activation of the inflammasome is a mechanism shared by many autoimmune and malignant disorders.

Nigella sativa attenuates iNOS pathway inflammation in liver cancer

Environmental Health and Preventive MedicineBecause iNOS activation of inflammation is a key process in a multitude of inflammatory disorders including a host of autoimmune diseases, a study published in Environmental Health and Preventative Medicine showing value in hepatocellular carcinoma is of is of particular importance:

“Nitric oxide (NO) and inducible nitric oxide synthase enzyme (iNOS) have been implicated in various tumors….Nigella sativa (NS) has been shown to have specific health benefits. The aim of this study was to investigate the in vivo modulation of the iNOS pathway by NS ethanolic extract (NSEE) and the implications of this effect as an antitumor therapeutic approach against diethylnitrosamine (DENA)-induced hepatocarcinogenesis…Serum AFP, NO, TNF-α, and IL-6 levels and iNOS enzyme activity were significantly increased in rats treated with DENA. Significant up-regulation of liver iNOS mRNA and protein expression was also observed. Subsequent treatment with NSEE significantly reversed these effects and improved the histopathological changes in malignant liver tissue which appeared after treatment with DENA, without any toxic effect when given alone.”

This data inspired the authors to conclude:

“These results provide evidence that attenuation of the iNOS pathway and suppression of the inflammatory response mediated by TNF-α, and IL-6 could be implicated in the antitumor effect of NSEE. As such, our findings hold great promise for the utilization of NS as an effective natural therapeutic agent in the treatment of hepatocarcinogenesis.”

Cytotoxic effect against lung cancer

Asian Pacific Journal of Cancer PreventionAuthors of a study just published in the Asian Pacific Journal of Cancer Prevention report that Nigella sativa seed extract significantly reduces the viability of lung cancer cells:

Nigella sativa (N sativa), commonly known as black seed, has been used in traditional medicine to treat many diseases. The antioxidant, anti-inflammatory, and antibacterial activities of N sativa extracts are well known. Therefore, the present study was designed to investigate the anticancer activity of seed extract (NSE) and seed oil (NSO) of N sativa against a human lung cancer cell line…The results showed NSE and NSO significantly reduce the cell viability and alter the cellular morphology of A-549 cells in a concentration dependent manner. The percent cell viability was recorded as 75%, 50%, and 26% at 0.25, 0.5, and 1 mg/ml of NSE by MTT assay and 73%, 48%, and 23% at 0.25, 0.5, and 1 mg/ml of NSE by NRU assay. Exposure to NSO concentrations of 0.1 mg/ml and above for 24 h was also found to be cytotoxic. The decrease in cell viability at 0.1, 0.25, 0.5, and 1 mg/ml of NSO was recorded to be 89%, 52%, 41%, and 13% by MTT assay and 85%, 52%, 38%, and 11% by NRU assay, respectively. A-549 cells exposed to 0.25, 0.5 and 1 mg/ml of NSE and NSO lost their typical morphology and appeared smaller in size. The data revealed that the treatment of seed extract (NSE) and seed oil (NSO) of Nigella sativa significantly reduce viability of human lung cancer cells.

Nigella sativa inhibits breast cancer

PLOS ONEEvidence is mounting for the use of Nigella sativa against breast cancer. Similar to the prooxidant effect described above, a study published in PLoS One describes how thymoquinone inhibits tumor growth and induces apoptosis in breast cancer cells through p38 phosphorylation and ROS production:

“Due to narrow therapeutic window of cancer therapeutic agents and the development of resistance against these agents, there is a need to discover novel agents to treat breast cancer. The antitumor activities of thymoquinone (TQ), a compound isolated from Nigella sativa oil, were investigated in breast carcinoma in vitro and in vivo. Cell responses after TQ treatment were assessed by using different assays including MTT assay, annexin V-propidium iodide staining, Mitosox staining and Western blot. The antitumor effect was studied by breast tumor xenograft mouse model, and the tumor tissues were examined by histology and immunohistochemistry. The level of anti-oxidant enzymes/molecules in mouse liver tissues was measured by commercial kits. Here, we show that TQ induced p38 phosphorylation and ROS production in breast cancer cells. These inductions were found to be responsible for TQ’s anti-proliferative and pro-apoptotic effects. Moreover, TQ-induced ROS production regulated p38 phosphorylation but not vice versa. TQ treatment was found to suppress the tumor growth and this effect was further enhanced by combination with doxorubicin. TQ also inhibited the protein expression of anti-apoptotic genes, such as XIAP, survivin, Bcl-xL and Bcl-2, in breast cancer cells and breast tumor xenograft. Reduced Ki67 and increased TUNEL staining were observed in TQ-treated tumors. TQ was also found to increase the level of catalase, superoxide dismutase and glutathione in mouse liver tissues.”

Again we see increases in the profoundly important glutatione under the influence of thymoquinone. Note also that the antitumor effect of the conventional chemotherapeutic agent was enhanced.

“In conclusion, our study provides evidence for the mechanism of action of TQ in suppressing human breast carcinoma in both in vitro and in vivo models. We demonstrated that the anti-proliferative and pro-apoptotic effects of TQ are mediated through its induction effect on p38 and ROS signaling. Our results also indicate the anti-tumor effects of TQ in breast tumor xenograft mice and its ability to potentiate the antitumor effect of doxorubicin. TQ serves as a promising anticancer agent and further studies may provide important leads for its clinical application.”

Journal of Medicinal FoodA study published in the Journal of Medicinal Food also reports proapoptotic and antimetastatic effects of Nigella sativa for breast cancer:

“This study investigated the apoptotic, antimetastatic, and anticancer activities of supercritical carbon dioxide (SC-CO2) extracts of the seeds of N. sativa Linn. against estrogen-dependent human breast cancer cells (MCF-7)….Of the 12 extracts, 1 extract (A3) that was prepared at 60°C and 2500 psi (~17.24 MPa) showed selective antiproliferative activity against MCF-7 cells with an IC50 of 53.34±2.15 μg/mL. Induction of apoptosis was confirmed by evaluating caspases activities and observing the cells under a scanning electron microscope. In vitro antimetastatic properties of A3 were investigated by colony formation, cell migration, and cell invasion assays. The elevated levels of caspases in A3 treated MCF-7 cells suggest that A3 is proapoptotic. Further nuclear condensation and fragmentation studies confirmed that A3 induces cytotoxicity through the apoptosis pathway. A3 also demonstrated remarkable inhibition in migration and invasion assays of MCF-7 cells at subcytotoxic concentrations. Thus, this study highlights the therapeutic potentials of SC-CO2 extract of N. sativa in targeting breast cancer.”

Pharmacognosy ResearchAnd authors of a study published in Pharmacognosy Research also report activity of thymoquinone against breast cancer:

“The study addressed the anti-cancer efficiency of long-term in vitro treatment with thymoquinone towards human breast cancer cell lines MCF-7...The 50% inhibitory concentration (IC50) value determined using the proliferation assay was 25 μM thymoquinone. Late apoptotic cell percentage increased rapidly when treatment duration was increased to 24 h with 25 and 100 μM thymoquinone. Further analysis using cell cycle assay showed thymoquinone inhibition of breast cancer cell proliferation at minimal dose 25 μM and led to S phase arrest significantly at 72 h treatment. It was also noted elevation sub-G1 peak following treatment with 25 μM thymoquinone for 12 h. Increase in thymoquinone to 50 μM caused G2 phase arrest at each time-point studied…In general thymoquinone showed sustained inhibition of breast cancer cell proliferation with long-term treatment. Specificity of phase arrest was determined by thymoquinone dose.”

Asian Pacific Journal of Cancer PreventionAntiproliferative effects against breast cancer cells were also shown in a study published in the Asian Pacific Journal of Cancer Prevention:

“Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 μg/mL. Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h. Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.”

Nigella sativa protects against liver damage caused by tamoxifen

Canadian Journal of Physiology and PharmacologyProtection against the harmful toxic effects of chemotherapy is a critical component of cancer case management. A welcome study published in the Canadian Journal of Physiology and Pharmacology shows that thymoquinone from Nigella sativa protects against the hepatotoxicity of tamoxifen:

“One of the major reasons for terminating a clinical trial is the liver toxicity induced by chemotherapy. Tamoxifen (TAM) is an anti-estrogen used in the treatment and prevention of hormone-dependent breast cancer. Tamoxifen therapy may cause hepatic injury. The seeds of Nigella sativa, which contain the active ingredient thymoquinone (TQ), have been used in folk medicine for diverse ailments. TQ is reported to possess anticancer and hepatoprotective effects. In this study, the protective effects of TQ against TAM-induced hepatotoxicity in female rats were evaluated. Four groups of rats were used: control; TAM; TQ; TAM+TQ. TAM (45 mg·(kg body mass)(-1)·day(-1), by intraperitoneal injection (i.p.), for 10 consecutive days) resulted in elevated serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, total bilirubin, and gamma glutamyl transferase, as well as depletion of reduced glutathione in the liver and accumulation of lipid peroxides. Also, TAM treatment inhibited the hepatic activity of superoxide dismutase. Further, it raised the levels of tumor necrosis factor alpha in the liver and induced histopathological changes. Pretreatment with TQ (50 mg·(kg body mass)(-1)·day(-1); orally, for 20 consecutive days, starting 10 days before TAM injection) significantly prevented the elevation in serum activity of the assessed enzymes. TQ significantly inhibited TAM-induced hepatic GSH depletion and LPO accumulation. Consistently, TQ normalized the activity of SOD, inhibited the rise in TNF-α and ameliorated the histopathological changes. In conclusion, TQ protects against TAM-induced hepatotoxicity.”

Again we see beneficial effects on glutatione metabolism.

Protection against kidney toxicity of cisplatin

Iranian Journal of Kidney DiseasesWhile on the topic of protection unwanted against damage done by cytotoxic chemotherapy, we can appreciate a study published in the Iranian Journal of Kidney Diseases reporting evidence that Nigella sativa offers some protection against the nephrotoxic effects of cisplatin:

“Thirty rats were divided into 3 groups to receive distilled water (control group), cisplatin (3 mg/kg per body weight for 3 days), and cisplatin and alcoholic extract of NS (100 mg/kg per body weight). Biochemical and histopathologic parameters were compared between the three groups on days 14 and 42 of the study…Cisplatin-induced nephrotoxicity was confirmed in our study…Histology of the kidneys exposed to cisplatin showed significant kidney injury, but the rats treated with NS showed a relatively well-preserved architectureNigella sativa seeds had nonsignificant effects on biochemical parameters, although the histopathologic properties of the kidneys relatively recovered after NS use.”

Nigella sativa benefits for the brain, mood and cognition

Journal of EthnopharmacologyConsidering the immune-regulating and anti-inflammatory virtues of Nigella sativa it stands to reason that there would be benefits for the brain. A study published in the Journal of Ethnopharmacology reports that it helps stabilize mood, reduce anxiety and cognition in adolescent males.

“Previous studies conducted on animals linked consumption of Nigella sativa L. seeds (NS) to decreased anxiety and improved memory. The present study, which was carried out at a boarding school in Bangladesh, was designed to examine probable effect of NS on mood, anxiety and cognition in adolescent human males…Forty-eight healthy adolescent human males aged between 14 to 17 years were randomly recruited as volunteers and were randomly split into two groups: A (n=24) and B (n=24). The treatment procedure for group A and B were one capsule of 500 mg placebo and 500 mg NS respectively once daily for four weeks. All the volunteers were assessed for cognition with modified California verbal learning test-II (CVLT-II), mood with Bond–Lader scale and anxiety with State–Trait Anxiety Inventory (STAI) at the beginning and after four weeks of either NS or placebo ingestion…Over the 4 weeks study period, the use of NS as a nutritional supplement been observed to- stabilize mood, decrease anxiety and modulate cognition positively.”

Relieving neuroinflammation of depression

Journal of Pharmacy & BioAllied SciencesIt’s well known than neuroimmune inflammation plays a fundamental role in depression. Authors of a study published in the Journal of Pharmacy & BioAllied Sciences present welcome evidence that Nigella sativa and thymoquinone may relieve depression by reducing neuroinflammation:

Neuroimmune factors have been proposed as contributors to the pathogenesis of depression. Beside other therapeutic effects including neuroprotective, antioxidant, anticonvulsant and analgesic effects, Nigella sativa and its main ingredient, thymoquinone (TQ), have been shown to have anti-inflammatory effects. In the present study, the effects of Nigella sativa hydro-alcoholic extract and thymoquinone was investigated on lipopolysaccharide- induced depression like behavior in rats…The results of the present study showed that hydro-alcoholic extract of Nigella sativa can prevent LPS-induced depression like behavior in rats. These results support the traditional belief on the beneficial effects of Nigella sativa in the nervous system.”

Thymoquinone ameliorates lead-induced brain damage

Experimental and Toxicologic PathologyEnvironmental toxicity is a concern for brain health; an exciting study published Experimental and Toxicologic Pathology indicates that thymoquinone from Nigella sativa protects against brain damage from lead:

“The present study aims to investigate the protective effects of thymoquinone, the major active ingredient of Nigella sativa seeds, against lead-induced brain damage in Sprague-Dawley rats. In which, 40 rats were divided into four groups (10 rats each). The first group served as control. The second, third and fourth groups received lead acetate, lead acetate and thymoquinone, and thymoquinone only, respectively, for one month. Lead acetate was given in drinking water at a concentration of 0.5 g/l (500 ppm). Thymoquinone was given daily at a dose of 20 mg/kg b.w. in corn oil by gastric tube. Control and thymoquinone-treated rats showed normal brain histology. Treatment of rats with lead acetate was shown to produce degeneration of endothelial lining of brain blood vessels with peri-vascular cuffing of mononuclear cells consistent to lymphocytes, congestion of choroid plexus blood vessels, ischemic brain infarction, chromatolysis and neuronal degeneration, microglial reaction and neuronophagia, degeneration of hippocampal and cerebellar neurons, and axonal demyelination. On the other hand, co-administration of thymoquinone with lead acetate markedly decreased the incidence of lead acetate-induced pathological lesions.”

Protection against Parkinson’s disease α-synuclein-induced synapse damage

Neuroscience LettersAgents that offer protection against α-synuclein toxicity are welcome in the treatment of Parkinson’s disease and dementia. A study recently published in Neuroscience Letters presents evidence that thymoquinone from Nigella sativa has this property:

“The present study aimed to determine whether TQ protects against α-synuclein (αSN)-induced synaptic toxicity in rat hippocampal and human induced pluripotent stem cell (hiPSC)-derived neurons. Here, we report that αSN decreased the level of synaptophysin, a protein used as an indicator of synaptic density, in cultured hippocampal and hiPSC-derived neurons. However, simultaneous treatment with αSN and TQ protected neurons against αSN-induced synapse damage, as revealed by immunostaining. Moreover, administration of TQ efficiently induced protection in these cells against αSN-induced inhibition of synaptic vesicle recycling in hippocampal and hiPSC-derived neurons as well as against mutated P123H β-synuclein (βSN) in hippocampal neurons, as revealed by experiments using the fluorescent dye FM1-43. Using a multielectrode array, we further demonstrated that the treatment of hiPSC-derived neurons with αSN induced a reduction in spontaneous firing activity, and cotreatment with αSN and TQ partially reversed this loss. These results suggest that TQ protects cultured rat primary hippocampal and hiPSC-derived neurons against αSN-induced synaptic toxicity and could be a promising therapeutic agent for patients with Parkinson’s disease and dementia with Lewy bodies.

Thymoquinone prevents β-amyloid neurotoxicity of Alzheimer’s disease

Cellular and Molecular NeurobiologyOf great interest in the prevention of Alzheimer’s disease are agents that may protect agains β-amyloid neurotoxicity. Here too thymoquinone has effect as reported in a study published in Cellular and Molecular Neurobiology:

Thymoquinone (TQ), a bioactive constituent of Nigella sativa Linn (N. sativa) has demonstrated several neuropharmacological attributes. In the present study, the neuroprotective properties of TQ were investigated by studying its anti-apoptotic potential to diminish β-amyloid peptide 1-40 sequence (Aβ1-40)-induced neuronal cell death in primary cultured cerebellar granule neurons (CGNs)…Pretreatment of CGNs with TQ (0.1 and 1 μM) and subsequent exposure to 10 μM Aβ1-40 protected the CGNs against the neurotoxic effects of the latter. In addition, the CGNs were better preserved with intact cell bodies, extensive neurite networks, a loss of condensed chromatin and less free radical generation than those exposed to Aβ1-40 alone. TQ pretreatment inhibited Aβ1-40-induced apoptosis of CGNs via both extrinsic and intrinsic caspase pathways. Thus, the findings of this study suggest that TQ may prevent neurotoxicity and Aβ1-40-induced apoptosis. TQ is, therefore, worth studying further for its potential to reduce the risks of developing Alzheimer’s disease.”

 Nigella sativa protects and promotes healing from nerve trauma

Pathologie BiologieA study published Pathologie Biologie reports that Nigella sativa improves the neurodegeneration typical after nerve trauma:

“The aim of this study was designed to evaluate the possible protective effects of Nigella sativa (NS) on the neuronal injury in the sciatic nerve of rats. The rats were randomly allotted into one of the three experimental groups: A (control), B (only trauma) and C (trauma and treated with NS); each group contain 10 animals… To date, no histopathological changes of neurodegeneration in the sciatic nerve after trauma in rats by NS treatment have been reported. Results showed in the group B (only trauma), the neurons of sciatic nerve tissue became extensively dark and degenerated with picnotic nuclei. Treatment of NS markedly reduced degenerating neurons after trauma and the distorted nerve cells were mainly absent in the NS-treated rats. The morphology of neurons in groups treated with NS was well protected, but not as neurons of the control group. The number of neurons in sciatic nerve tissue of group B (only trauma) was significantly less than both control and treated with NS groups. The morphology of neurons revealed that the number of neurons were significantly less in group B compared to control and group C rats’ motor neurons anterior horn spinal cord tissue. We conclude that NS therapy causes morphologic improvement on neurodegeneration in sciatic nerve after trauma in rats.”

Nigella sativa for osteoporosis

Evidence-Based Complementary and Alternative MedicineConsidering that inflammation plays a key role in osteoporosis, it’s reasonable to investigate the use Nigella sativa as described in a paper in Evidence-Based Complementary and Alternative Medicine:

“Animal studies have shown that NS and TQ may be used for the treatment of diabetes-induced osteoporosis and for the promotion of fracture healing. The mechanism involved is unclear, but it was postulated that the antioxidative, and anti-inflammatory activities may play some roles in the treatment of osteoporosis as this bone disease has been linked to oxidative stress and inflammation. This paper highlights studies on the antiosteoporotic effects of NS and TQ, the mechanisms behind these effects and their safety profiles. NS and TQ were shown to inhibit inflammatory cytokines such as interleukin-1 and 6 and the transcription factor, nuclear factor κB. NS and TQ were found to be safe at the current dosage for supplementation in human with precautions in children and pregnant women. Both NS and TQ have shown potential as antiosteoporotic agent but more animal and clinical studies are required to further assess their antiosteoporotic efficacies.”

Inhibition of osteoporosis by Nigella sativa

BMC Complementary & Alternative MedicineIn an exciting study published in the BMC Complementary and Alternative Medicine, investigators report the reversal of osteoporosis in subjects whose ovaries had been removed:

“There is a direct relationship between the lack of estrogen after menopause and the development of osteoporosis…Nigella Sativa (NS) has been shown to have beneficial effects on bone and joint diseases. The present study was conducted to elucidate the protective effect of Nigella Sativa on osteoporosis produced by ovariectomy in rats…Female Wistar rats aged 12-14 months were divided into three groups: sham-operated control (SHAM), ovariectomized (OVX), and ovariectomized supplemented with nigella sativa (OVX-NS) orally for 12 weeks; 4 weeks before ovariectomy and 8 weeks after…OVX rats showed significant decrease in plasma Ca(+2), accompanied by a significant increase in plasma ALP, amino terminal collagen type 1 telopeptide, MDA, nitrates, TNF-α and IL-6. These changes were reversed by NS supplementation in OVX-NS group to be near SHAM levels. Histological examination of the tibias revealed discontinuous eroded bone trabeculae with widened bone marrow spaces in OVX rats accompanied by a significant decrease in both cortical and trabecular bone thickness compared to Sham rats. These parameters were markedly reversed in OVX-NS rats. Histological examination of the liver showed mononuclear cellular infiltration and congestion of blood vessels at the portal area in OVX rats which were not found in OVX-NS rats.”

Their data supported this exciting conclusion:

“It can be concluded that NS has shown potential as a safe and effective antiosteoporotic agent, which can be attributed to its high content of unsaturated fatty acids as well as its antioxidant and anti-inflammatory properties.”

Nigella sativa helps with psoriasis

Pharmacognosy MagazineConsidering its antiinflammatory and immunomodulating characteristics it seems a good bet that Nigella sativa would help with psoriasis as described in a study published in Pharmacognosy Magazine:

“The screening of antipsoriatic activity of 95% of ethanolic extract of Nigella sativa seeds by using mouse tail model for psoriasis and in vitro antipsoriatic activity was carried out by SRB Assay using HaCaT human keratinocyte cell lines….The ethanolic extract of Nigella sativa seeds extract produced a significant epidermal differentiation, from its degree of orthokeratosis (71.36±2.64) when compared to the negative control (17.30±4.09%)…The 95% ethanolic extract of Nigella sativa shown IC50 239 μg/ml, with good antiproliferant activity compared to Asiaticoside as positive control which showed potent activity with IC50 value of 20.13 μg/ml. From the present study it can be said that topical application of 95% ethanolic extract of Nigella sativa seeds has antipsoriatic activity and the external application is be beneficial in the management of psoriasis.”

Assists in treatment of vitiligo

Iranian Red Crescent Medical JournalNIgella sativa is an agent to consider in case management of any autoimmune disorder including vitiligo, for which it showed benefit in a study published in the Iranian Red Crescent Medical Journal:

Vitiligo is one of the autoimmune skin diseases that destroy the melanocytes of the skin…The aim of this study was to compare the effect of Nigella sativa and fish oil on vitiligo lesions of the patients referred to a dermatology clinic…After six months, a mean score of VASI decreased from 4.98 to 3.75 in patients applying topical Nigella sativa and from 4.98 to 4.62 in those using topical fish oil…In the current study, administration of Nigella sativa and fish oil significantly decreased skin lesions size, indicating an improvement in clinical condition…the depigmented areas were reduced over time and the skin color showed improvement. One reason for this positive response to treatment is the thymoquinone component of Nigella sativa…Thymoquinone can simulate the activity of acetylcholine, which causes the release of melanin and darkening of the skin through stimulation of cholinergic receptors. In addition, Nigella sativa oil administration was tolerable as well as safe and improved oxidative stress and clinical condition of patients…It was also shown that this type of treatment has no significant side effects and resulted in high patient satisfaction and acceptance.”

The authors state in conclusion:

“Nigella sativa oil and fish oil were effective in reduction the size of patient’s lesions; however, Nigella sativa was more effective in comparison to the fish oil. Therefore, using Nigella sativa with the major drugs in the treatment of vitiligo is recommended.”

Topical treatment of allergic rhinitis

Anti-Inflammatory & Anti-Allergy Agents in Medicinal ChemistryAllergic rhinitis as a chronic inflammatory disorder also responds to Nigella sativa applied topically as reported in Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry:

Allergic rhinitis (AR) is the most common manifestation of atopic reaction to inhaled allergens. It is a chronic inflammatory disease which may first appear at any age, but the onset is usually during childhood or adolescence…The individuals in the active group received N. sativa oil and the control group individuals received ordinary food oil in the form of nasal drops for 6 weeks…After the 6 weeks treatment course, 100% of the patients in the mild active group became symptoms free; while in moderate active group 68.7% became symptoms free and 25% were improved; while in severe active group 58.3% became symptoms free and 25% were improved. In addition, 92.1% of total patients in the active group demonstrated improvement in their symptoms or were symptoms free, while the corresponding value was 30.1% in the control group. At the end of 6 weeks of treatment with topical use, the improvement in tolerability of allergen exposure in active group became 55.2% which was significant as compared with control group which was accounted for 20% at the same time…Topical application of black seed oil was effective in the treatment of allergic rhinitis, with minimal side effects.”

Nigella sativa protects against radiation damage

Journal of Investigative SurgeryRadiation therapy can produce substantial ‘collateral damage’. Authors of a study just published in the Journal of Investigative Surgery demonstrate that Nigella sativa reduces oxidative stress in animals subjected to total head irradiation:

“Many cancer patients treated with radiotherapy suffer severe side effects during and after their treatment. The aim of this study was to investigate the effects of irradiation and the addition of Nigella sativa oil (NSO) on the oxidant/antioxidant system in the liver tissue of irradiated rats…The control group received neither NSO nor irradiation but received 1-ml saline orally. The irradiation group (IR) received total head 5 gray (Gy) of gamma irradiation as a single dose, plus 1-ml saline orally. The IR plus NSO group received both total head 5 Gy of gamma irradiation as a single dose and 1 g/kg/day NSO orally through an orogastric tube starting one hour before irradiation and continuing for 10 days…Conclusions: NSO reduces oxidative stress markers and has antioxidant effects, which also augments the antioxidant capacity in the liver tissue of rats.”

Cutaneous and Ocular ToxicologyNigella sativa was shown to reduce radiation-induced cataracts in a study published in Cutaneous and Ocular Toxicology:

“The aim of this study was to investigate the antioxidant and radioprotective effects of Nigella sativa oil (NSO) and thymoquinone (TQ) against ionizing radiation-induced cataracts in lens after total cranium irradiation (IR) of rats with a single dose of 5 gray (Gy)…At the end of the 10th d, cataract developed in 80% of the rats in IR group only. After IR, cataract rate dropped to 20% and 50% in groups which were treated with NSO and TQ, respectively, and was limited at grades 1 and 2. Nitric oxide synthase activity, nitric oxide and peroxynitrite levels in the radiotherapy group were higher than those of all other groups. Conclusions: The results implicate a major role for NSO and TQ in preventing cataractogenesis in ionizing radiation-induced cataracts in the lenses of rats, wherein NSO were found to be more potent.”

PhytomedicineAnd protection from radiation-induced damage to brain tissue was demonstrated in a study recently published in the journal Phytomedicine designed…

“To investigate Nigella sativa oil (NSO) and Thymoquinone (TQ) for their antioxidant effects on the brain tissue of rats exposed to ionizing radiation….Levels of NO· and ONOO(-), and enzyme activity of NOS in brain tissue of the rats treated with NSO or TQ were found to be lower than in received IR alone (p<0.002) Nigella sativa oil (NSO) and its active component, TQ, clearly protect brain tissue from radiation-induced nitrosative stress.

 Activity against Staphylococcal and fungal skin infections

Pakistan Journal of Biological SciencesNigella sativa is a benevolent agent in the treatment of skin infection and inflammation as documented by a study published in the Pakistan Journal of Biological Sciences:

“Nigella sativa has been used for a long time in Jordanian folk medicine to treat skin diseases like microbial infections and inflammation. Therefore, the present study was conducted to assess the healing efficacy of petroleum ether extract of Nigella sativa seeds (fixed oil) on staphylococcal-infected skin. Male BALB/c mice were infected with 100 microL of Staphylococcus aureus (ATCC 6538)… Application of treatments for each group (100 microL sterile saline, 100 microL chloramphenicol (10 microg/mouse) and Nigella sativa fixed oil at a dose of 50, 100 or 150 microL/mouse) was performed at the site of infection… At day 3 and 5 after infection, total White Blood Cells (WBCs) count; differential and absolute differential WBC counts and the number of viable bacteria present in the skin area were measured…Results indicated that fixed oil of Nigella sativa seeds enhance healing of staphylococcal-infected skin by reducing total and absolute differential WBC counts, local infection and inflammation, bacterial expansion and tissue impairment. These effects provide scientific basis for the use of Nigella sativa in traditional medicine to treat skin infections and inflammations.

Journal of EthnopharmacologyThe authors of a study published in the Journal of Ethnopharmacology report effectiveness against fungal skin infections (dermatophytes):

“The antifungal activity of ether extract of Nigella sativa seed and its active principle thymoquinone was tested against eight species of dermatophytes: four species of Trichophyton rubrum and one each of Trichophyton interdigitale, Trichophyton mentagrophytes, Epidermophyton floccosum and Microsporum canis. Agar diffusion method with serial dilutions of ether extract of Nigella sativa, thymoquinone and griseofulvin was employed…The minimum inhibitory concentration (MIC) was considered as the minimum concentration of the drug, which inhibited 80–100% of the fungal growth. The MICs of the ether extract of Nigella sativa and thymoquinone were between 10 and 40 and 0.125 and 0.25 mg/ml…These results denote the potentiality of Nigella sativa as a source for antidermatophyte drugs and support its use in folk medicine for the treatment of fungal skin infections.”

Case report of seroreversion in HIV

Afr J Tradit Complement Altern Med.A case report published in the African Journal of Traditional, Complementary, and Alternative Medicines presents unexpected results in the treatment of HIV:

“Nigella sativa had been documented to possess many therapeutic functions in medicine but the least expected is sero-reversion in HIV infection which is very rare despite extensive therapy with highly active anti-retroviral therapy (HAART). This case presentation is to highlight the complete recovery and sero-reversion of adult HIV patient after treatment with Nigella sativa concoction for the period of six months. The patient presented to the herbal therapist with history of chronic fever, diarrhoea, weight loss and multiple papular pruritic lesions of 3 months duration. Examination revealed moderate weight loss, and the laboratory tests of ELISA (Genscreen) and western blot (new blot 1 & 2) confirmed sero-positivity to HIV infection with pre-treatment viral (HIV-RNA) load and CD4 count of 27,000 copies/ml and CD4 count of 250 cells/ mm(3) respectively. The patient was commenced on Nigella sativa concoction 10 mls twice daily for 6 months. He was contacted daily to monitor side-effects and drug efficacy. Fever, diarrhoea and multiple pruritic lesions disappeared on 5th, 7th and 20th day respectively on Nigella sativa therapy. The CD4 count decreased to 160 cells/ mm3 despite significant reduction in viral load (≤1000 copies/ml) on 30th day on N. sativa. Repeated EIA and Western blot tests on 187th day on Nigella sativa therapy was sero-negative. The post therapy CD4 count was 650 cells/ mm(3) with undetectable viral (HIV-RNA) load. Several repeats of the HIV tests remained sero-negative, aviraemia and normal CD4 count since 24 months without herbal therapy. This case report reflects the fact that there are possible therapeutic agents in Nigella sativa that may effectively control HIV infection.

Improvement in semen quality

PhytomedicineAnother study published in Phytomedicine presents evidence from a double-blind, placebo-controlled that Nigella sativa improves abnormal semen quality in infertility:

“Since Nigella sativa L. seed (N. sativa) has many uses including infertility in traditional medicine, the effects of Nigella sativa L. seed oil on abnormal semen quality in infertile men with abnormal semen quality are of interest. This study was conducted on Iranian infertile men with inclusion criteria of abnormal sperm morphology less than 30% or sperm counts below 20×10(6)/ml or type A and B motility less than 25% and 50% respectively. The patients in N. sativa oil group (n=34) received 2.5mlN. sativa oil and placebo group (n=34) received 2.5ml liquid paraffin two times a day orally for 2 months. At baseline and after 2 months, the sperm count, motility and morphology and semen volume, pH and round cells as primary outcomes were determined in both groups. Results showed that sperm count, motility and morphology and semen volume, pH and round cells were improved significantly in N. sativa oil treated group compared with placebo group after 2 months. It is concluded that daily intake of 5ml N. sativa oil for two months improves abnormal semen quality in infertile men without any adverse effects.”

Is Nigella sativa safe?

Advanced Pharmaceutical BulletinA study investigating the potential for liver toxicity was reported last year in the journal Advanced Pharmaceutical Bulletin:

“The aim of this study was to determine the toxic effect of Nigella sativa powder on the liver function which was evaluated by measuring liver enzymes and through histopathological examination of liver tissue…Twenty four male Sprague Dawley rats were allotted randomly to four groups including: control (taking normal diet); low dose (supplemented with 0.01 g/kg/day Nigella sativa); normal dose (supplemented with 0.1 g/kg/day Nigella sativa) and high dose (supplemented with 1 g/kg/day Nigella sativa)…To assess liver toxicity, liver enzymes measurement and histological study were done at the end of supplementation…The study showed that supplementation of Nigella sativa up to the dose of 1 g/kg supplemented for a period of 28 days resulted no changes in liver enzymes level and did not cause any toxicity effect on the liver function

The authors stated this conclusion regarding human consumption of Nigella sativa:

“With the evidence of normal ALT and AST level in blood and normal liver tissue in histology examination for all treatment groups, it is suggested that there are no toxic effect on liver function of Nigella sativa at different doses for 4 weeks period. As a conclusion, popular consumption of Nigella sativa powder by human did not cause any toxicity effect on the liver function and safe to be consumed for many purposes.”

 Protection against alcohol-induced liver injury

Chinese Journal of Natural MedicinesNot only is Nigella sativa safe for the liver, but a study published in the Chinese Journal of Natural Medicines provides data showing that it protects the liver against oxidative damage caused by alcohol:

Nigella sativa L. (Ranunculaceae) is considered as a therapeutic plant-based medicine for liver damage. In this study, the aim was to study the effect of Nigella sativa oil (NSO) pretreatment on ethanol-induced hepatotoxicity in rats…Rats were given Nigella sativa oil at doses of 2.5 and 5.0 mL·kg(-1), orally for 3 weeks, followed by oral ethanol (EtOH) administration (5 g·kg(-1)) every 12 h three times (binge model).”


Binge ethanol application caused significant increases in plasma transaminase activities and hepatic triglyceride and malondialdehyde (MDA) levels. It decreased hepatic glutathione (GSH) levels, but did not change vitamins E and vitamin C levels and antioxidant enzyme activities. NSO (5.0 mL·kg(-1)) pretreatment significantly decreased plasma transaminase activities, hepatic MDA, and triglyceride levels together with amelioration in hepatic histopathological findings.”

Based on these findings the authors conclude:

“NSO pretreatment may be effective in protecting oxidative stress-induced hepatotoxicity after ethanol administration.”

Practical use of Nigella sativa

Nigella sativa seeds 3The foregoing sampling of studies from the scientific literature on Nigella sativa should not be construed as an endorsement for its use in any specific case or condition. It is a presentation of the extraordinary scope of action and clinical potential of an agent that I am finding valuable in practice. Colleagues who are interested in knowing the particular Nigella sativa whole seed extract that I am using are welcome to contact me. For the general reader, I caution against taking anything (especially something found on the internet) without having first discussed it with your knowledgeable health care practitioner who has the background and depth to advise on how this may fit into your treatment or health maintenance plan.