Black cumin seed oil, a.k.a black seed oil (N. sativa or NS) and thymoquinone have been thoroughly studied for decades. With the heightened interest in ingredients that support immune health, taking a look at the extensive research done with regards to NS and its phytochemical compounds is appropriate. One statement in particular from International Immunology summarizes the need to consider NS oil as a viable choice for immune support,
“Experimental evidence suggests that N. sativa extracts and TQ (thymoquinone) can potentially be employed in the development of effective therapeutic agents towards the regulation of immune reactions implicated in various infectious and non-infectious conditions[i].”
Another broad statement from Iranian Journal of Basic Medical Science states;
“NS seeds have antimicrobial effects against different pathogens, including bacteria, viruses, schistosomes, and fungus. [ii]”
The following is a recap of the latest research showing the impact which NS can have in multiple areas of immune health.
Antiviral
The antiviral activity associated with Black Seed may be due to mechanisms happening at the cellular level or by boosting the immune system to fight against the pathogens. Although at this time more research needs to be done to pinpoint which mechanism is the principal driver of immune support, cell culture studies indicate NS has high efficacy in treating many types of viruses[iii]. The list of known viruses and the positive impact NS can have on these viruses is extensive. A review of studies published in Pharmacology OnLine Newsletter found effectiveness on murine cytomegalovirus infection, avian influenza (H9N2), Schistosoma Mansoni Infection, PPR virus, Broad bean mosaic virus, HIV, Hepatitis C Virus, Zucchini Yellow Mosaic Virus, and Papaya Ring Spot Virus[iv]. Additional in vivo studies indicate efficacy treating highly pathogenic avian influenza (HPAI/H7N3/HSN1) viruses xxxiv. The effects of NS were also tested on the replication of coronavirus and found a significant drop in the viral load when NS was added to coronavirus infected cells[v]. Other studies have confirmed the impact of NS on reducing viral load too[vi].
There are multiple mechanisms of action concerning how the antiviral effect is realized using NS oil and will be covered later in this paper. At this time, it is unclear which component(s) in NS are directly responsible for these antiviral activities. The benefits may be due to the Thymoquinone constituent, or some other Thymoquinone precursors. It is also possible that the activity is due to the proper composition of fatty acids, monoterpenoid, or the precise combination of all these components. This would be found in cold-pressed NS seeds, but not necessarily found in a CO2 or other extraction of stand-alone thymoquinone.[vii][viii]
Anti-inflammatory
Inflammation is a vital part of the immune system’s response to injury and infection. It is the body’s way of signaling the immune system to heal and repair damaged tissue, as well as defend itself against foreign invaders, such as viruses and bacteria. If though, the inflammatory process goes on for too long or if the inflammatory response occurs in places where it is not needed, it can lead to other more serious health challenges such as cardiovascular problems, immune disorders, etc. Being able to support the body’s ability to reduce chronic inflammation can be extremely beneficial. NS and TQ have shown to be helpful as an anti-inflammatory.[ix]
Antifungal
Different extracts of NS and TQ have exhibited powerful fungicidal activity against dermatophyte strains[x]. Dermatophytes are a common label for types of fungus, primarily impacting the skin, hair, and nails. Examples would be ringworm, toenail fungus, athlete’s foot, and jock itch.
Antibacterial
The use of TQ from NS has also been extensively studied with regard to bacterial infections. TQ obtained from seeds of NS revealed broader spectrum activities against multiple strains of gram-positive and gram-negative bacteria[xi], including Bacillus, Listeria, Enterococcus, Micrococcus, Staphylococcus, Pseudomonas, Escherichia, and Salmonella.[xii]
What makes NS and TQ great for Immune System Support?
While the information above backs the use of NS and TQ in multiple areas of immune health challenges, understanding the underlying mechanisms of action found with NS helps to substantiate the many possible areas in which NS can be used.
Immunomodulatory
Immune-modulating substances are a type of immunotherapy that enhances the body’s immune response. This can be either stimulates or suppresses the immune system and may help the body fight abnormal cell production, infection, or other diseases. Simply put, immunomodulating substances help “balance” the immune system and its response. In the case of NS and TQ, research shows that they can be used towards the regulation of immune reactions implicated in various infectious and non-infectious conditions[xiii]. Additionally, one published study stated, “The oil and certain active ingredients showed beneficial immunomodulatory properties, augmenting the T cell- and natural killer cell-mediated immune responses.[xiv]”
Antioxidant
Recent clinical trials have found that antioxidant supplementation can significantly improve certain immune responses. Adequate amounts of neutralizing antioxidants are required to prevent damage to immune cells. An adequate intake of antioxidants is essential for an efficient function of the immune system and important for the effects on immune responses[xv]. NS has shown to improve the action of antioxidant enzymes (catalase, glutathione peroxidase, and glutathione-S-transferase) and acts as a free radical scavenger[xvi].
Cytokine Production
Cytokines interact with cells of the immune system to regulate the body’s response to disease and infection. Some cytokines stimulate the immune system, and others slow it down. Immune cells use cytokines as messengers to other immune cells. Examples of cytokines are; chemokines, interferons, interleukins, lymphokines, and tumor necrosis factor.
NS enhances the production of cytokines, including interleukin-3[xvii], interleukin-1 beta[xviii] and interferon (INF)-gamma[xix]. Focusing on just one of these examples, INF-gamma is critical to both innate and adaptive immunity. Innate immunity is something you are born with and is considered the body’s first line of defense against disease. It includes the skin, secretions (mucous, enzymes, tears), and even immune cells such as neutrophils (mentioned later). Adaptive or often called acquired immunity develops as we age. As we get exposed to diseases, allergens, and vaccines, we produce the antibodies to fight off those foreign invaders to the body. INF-gamma also functions as the primary activator of macrophages, in addition to stimulating natural killer (NK) cells and neutrophils.
Lymphocytes Production
Lymphocytes are white blood cells that are crucial to our immune systems. There are three main types known as T cells, B cells, and natural killer (NK) cells. Lymphocytes are part of our immune defense and act to recognize antigens, produce antibodies, and destroy harmful cells. T cells get their name because they are developed in the thymus gland and are essential in immunity because they recognize antigens and can bind to them. B cells get their name because they mature in the bone marrow. They recognize and attach to specific antigens too. Natural killer cells are known to be cytotoxic. This means that they can kill other cells. NK cells are an important part of the immune system because they can recognize virally infected cells, as well as some types of tumor cells, and kill them before they cause harm.
NS has shown multiple benefits in the area of supporting lymphocyte activity and production, these include, enhanced splenocyte proliferation and significantly enhanced NK cytotoxic activity [xx]. NS also augments T cell and NK cell-mediated immune responses.[xxi]
T Helper Cells
Helper T cells are arguably the most critical cells in adaptive immunity, as they are required for almost all adaptive immune responses. They not only help activate B cells to secrete antibodies and macrophages to destroy ingested microbes, but they also help activate cytotoxic T cells to kill infected target cells[xxii]. NS has shown to benefit immune function possibly due to the increase in number and function of CD4+ T cells[xxiii]. CD4 T-cells are considered “helper” cells because they do not neutralize infections but rather trigger the body’s response to infections[xxiv].
In addition, NS has shown to favor the secretion of Th2, versus Th1[xxv] or, in some cases, balance the Th1/Th2 ratio.[xxvi] Th1 cells typically deal with infections by viruses and certain bacteria. They are the body’s first line of defense against any pathogen that gets inside our cells. Th1 cells tend to be pro-inflammatory. Th2 cells, on the other hand, typically deal with bacteria, toxins, and allergens.
Immunopotentiation
Immunopotentiation can be defined as a process that directly enhances one or more specific immune functions or modifies one or more components of the complex immunoregulatory network to achieve its effects through indirect mechanisms. With regards to NS, the immunopotentiating impact is mediated through stimulation of macrophage phagocytic activity either directly or via activation of lymphocytes[xxvii].
Increased phagocytosis
Treatment with N. sativa oil significantly increased the phagocytic activity and phagocytic index of macrophages.[xxviii] Macrophages are immune cells that engulf (eats) bacteria, viruses, fungi, and even parasites. NS has shown to have a positive effect on macrophages in multiple ways.[xxix][xxx]
Full Spectrum Oil
Using the words full-spectrum is becoming ever more popular these days. The scientific community has realized the need to extract the phytochemicals and nutritional components in their full and natural ratios to achieve proper health benefits. NS is most commonly known for four phytochemical compounds- thymoquinone, p-cymene, carvacrol, and its free fatty acids. But as mentioned previously, there are numerous other compounds found in a full-spectrum oil. Examples are; sterols and saponins, phenolic compounds, alkaloids, novel lipid constituents, and volatile oils of varying composition[xxxi]. Key phytochemicals such as the phytosterols are important to mention due to their nutraceutical and medicinal benefits in lowering LDL cholesterol and total cholesterol levels[xxxii]. The major sterols identified were β-sitosterol, campesterol, stigmasterol, and 5-avenasterol[xxxiii][xxxiv]. Tocopherols found in NS, and other plants are well recognized for their antioxidant potential. NS also contains melanin. A study done with melanin derived from NS showed an impact on the immune system primarily IL-8[xxxv].
What appears to work best to achieve a balanced and full-spectrum NS oil is the use of fresh black cumin seeds and cold-pressed extraction. These two combine to yield a standardized full-spectrum oil with the proper ratios of thymoquinone, p-cymene, carvacrol, free fatty acids, and the other phytochemicals mentioned above. These precise ratios contribute to the synergistic effects available in NS oil.
Conclusion
Taking a look back over the research, it is quite evident that there are multiple potential mechanisms of action with regard to NS use and immune health. Whether those mechanisms are direct or indirect, there is a need to consider it for any immune health product. The fact that NS has shown to be beneficial in both bacterial and viral conditions, as well as the abundance of science, put it in the upper echelon of dietary ingredients.
[i] Majdalawieh A, Fayyad M, Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: A comprehensive review, International Immunopharmacology 2015 Sep;28(1):295-304. doi: 10.1016/j.intimp.2015.06.023.
[ii] Forouzanfar F, Fazly B, Hosseinzadeh B, Black cumin (Nigella sativa) and its constituent (thymoquinone): A review on antimicrobial effects, Iranian Journal of Basic Medical Science 17(12):929-38 December 2014
[iii] Molla S, Azad A, et al., A REVIEW ON ANTIVIRAL EFFECTS OF NIGELLA SATIVA L., PharmacologyOnline Newsletter 2019 vol.2 47-53
[iv] Molla S, Azad A, et al., A REVIEW ON ANTIVIRAL EFFECTS OF NIGELLA SATIVA L., PharmacologyOnline Newsletter 2019 vol.2 47-53
[v] Ulasli M, Gurses SA, Bayraktar R, et al. The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family. Mol Biol Rep. 2014;41(3):1703–1711. doi:10.1007/s11033-014-3019-7
[vi] Forouzanfar F, Fazly B, Hosseinzadeh B, Black cumin (Nigella sativa) and its constituent (thymoquinone): A review on antimicrobial effects, Iranian Journal of Basic Medical Science 17(12):929-38 December 2014
[vii] [vii] Salem M, Immunomodulatory and therapeutic properties of the Nigella sativa L. seed., Int Immunopharmacol. 2005 Dec;5(13-14):1749-70
[viii] Forouzanfar F, Fazly B, Hosseinzadeh B, Black cumin (Nigella sativa) and its constituent (thymoquinone): A review on antimicrobial effects, Iranian Journal of Basic Medical Science 17(12):929-38 December 2014
[ix] Gholamnezhad Z, Keyhanmanesh R, Boskabady M, Anti-inflammatory, antioxidant, and immunomodulatory aspects of Nigella Sativa for its preventive and bronchodilatory effects on obstructive respiratory diseases: A review of basic and clinical evidence, Journal of Functional Foods Volume 17, August 2015, Pages 910-927
[x] Mahmoudvand H, Sepahvand A, Jahanbakhsh S, Ezatpour B, Ayatollahi Mousavi S, A Evaluation of antifungal activities of the essential oil and various extracts of Nigella sativa and its main component, thymoquinone against pathogenic dermatophyte strains. J Mycol Med. 2014 Dec; 24(4):e155-61.
[xi] Hosseinzadeh et al., Antibacterial Activity of Total Extracts and Essential oil of Nigella Sativa L. Seeds in Mice 123, Pharmacolgyonline 2: 429-435 (2007)
[xii] Abdallah E, Black Seed (Nigella sativa) as antimicrobial drug: a mini-review. Novel Approaches in Drug Designing and Develop. 2017;3(2):1–5.
[xiii] Majdalawieh A, Fayyad, Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: A comprehensive review., Int Immunopharmacol. 2015 Sep;28(1):295-304. doi: 10.1016/j.intimp.2015.06.023.
[xiv] Salem M, Immunomodulatory and therapeutic properties of the Nigella sativa L. seed., Int Immunopharmacol. 2005 Dec;5(13-14):1749-70.
[xv] Hajian S. Positive effect of antioxidants on the immune system. Immunopathol Persa. 2015;1(1):e02.
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[xvii] Haq A, Abdullatif M, Lobo P, Khabar K, Sheth K, al-Sedairy S, Nigella sativa: effect on human lymphocytes and polymorphonuclear leukocyte phagocytic activity. Immunopharmacology. 1995 Aug;30(2):147-55.
[xviii] Haq A, Abdullatif M, Lobo P, Khabar K, Sheth K, al-Sedairy S, Nigella sativa: effect on human lymphocytes and polymorphonuclear leukocyte phagocytic activity. Immunopharmacology. 1995 Aug;30(2):147-55.
[xix] Forouzanfar F, Fazly B, Hosseinzadeh B, Black cumin (Nigella sativa) and its constituent (thymoquinone): A review on antimicrobial effects, Iranian Journal of Basic Medical Science 17(12):929-38 December 2014
[xx] Majdalawieh A, Hmaidan R, Carr R., Nigella sativa modulates splenocyte proliferation, Th1/Th2 cytokine profile, macrophage function, and NK anti-tumor activity. Ethnopharmacol. 2010 Sep 15;131(2):268-75. doi: 10.1016/j.jep.2010.06.030.
[xxi] Gholamnezhad Z, Keyhanmanesh R, Boskabady M, Anti-inflammatory, antioxidant, and immunomodulatory aspects of Nigella Sativa for its preventive and bronchodilatory effects on obstructive respiratory diseases: A review of basic and clinical evidence, Journal of Functional FoodsVolume 17, August 2015, Pages 910-927
[xxii] Alberts B, Johnson A, Lewis J, et al. Helper T Cells and Lymphocyte Activation. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26827/ Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002
[xxiii] Forouzanfar F, Fazly B, Hosseinzadeh B, Black cumin (Nigella sativa) and its constituent (thymoquinone): A review on antimicrobial effects, Iranian Journal of Basic Medical Science 17(12):929-38 December 2014
[xxiv] Luckheeram R. Zhou R, Verma A, et al. CD4+ T cells: differentiation and functions. Clinical and Developmental Immunology. 2012:2012:925135. doi:10.1155/2012/925135
[xxv] Majdalawieh A, Hmaidan R, Carr R., Nigella sativa modulates splenocyte proliferation, Th1/Th2 cytokine profile, macrophage function and NK anti-tumor activity. Ethnopharmacol. 2010 Sep 15;131(2):268-75. doi: 10.1016/j.jep.2010.06.030.
[xxvi] Gholamnezhad Z, Keyhanmanesh R, Boskabady M, Anti-inflammatory, antioxidant, and immunomodulatory aspects of Nigella Sativa for its preventive and bronchodilatory effects on obstructive respiratory diseases: A review of basic and clinical evidence, Journal of Functional FoodsVolume 17, August 2015, Pages 910-927
[xxvii] Fararh K, Atoji Y, Shimizu Y, Shiina T, Nikami H, Takewaki T., Mechanisms of the hypoglycaemic and immunopotentiating effects of Nigella sativa L. oil in streptozotocin-induced diabetic hamsters. Res Vet Sci. 2004 Oct;77(2):123-9.
[xxviii] Fararh K, Atoji Y, Shimizu Y, Shiina T, Nikami H, Takewaki T., Mechanisms of the hypoglycaemic and immunopotentiating effects of Nigella sativa L. oil in streptozotocin-induced diabetic hamsters. Res Vet Sci. 2004 Oct;77(2):123-9.
[xxix] Haq A, Abdullatif M, Lobo P, Khabar K, Sheth K, al-Sedairy S, Nigella sativa: effect on human lymphocytes and polymorphonuclear leukocyte phagocytic activity. Immunopharmacology. 1995 Aug;30(2):147-55.
[xxx] Haq A, Abdullatif M, Lobo P, Khabar K, Sheth K, al-Sedairy S, Nigella sativa: effect on human lymphocytes and polymorphonuclear leukocyte phagocytic activity. Immunopharmacology. 1995 Aug;30(2):147-55.
xxxv Ulasli M, Gurses S, et al., The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family Mol Biol Rep (2014) 41:1703–1711 DOI 10.1007/s11033-014-3019-7
xxxiv Umar S, Munir M, Subhan S, et al., Protective and antiviral activities of Nigella sativa against avian influenza
(H9N2) in turkeys, Journal of the Saudi Society of Agricultural Sciences (2016)
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[xxxiii] Matthaus B., Özcan M. M. Fatty acids, tocopherol, and sterol contents of some nigella species seed oil. Czech Journal of Food Sciences. 2011;29(2):145–150.
[xxxiv] Cheikh-Rouhou S., Besbes S., Hentati B., Blecker C., Deroanne C., Attia H. Nigella sativa L.: chemical composition and physicochemical characteristics of lipid fraction. Food Chemistry. 2007;101(2):673–681.
[xxxv] El-Obeid A, Hassib A, Pontén A, Westermark B, Effect of herbal melanin on IL-8: A possible role of Toll-like receptor 4 (TLR4), Biochemical and Biophysical Research Communications Volume 344, Issue 4, 16 June 2006, Pages 1200-1206