Xbrain’s Organic Virgin Black Seed Oil is unrefined oil cold pressed from the seeds of black cumin, Nigella sativa. Black cumin has been used in traditional medicine for thousands of years, in the Unani system of medicine in Middle Eastern Countries. It is used as a painkiller, to help with abscesses, against parasites, such as intestinal worms, and nasal congestion. Nowadays, many of these actions, and more, have been confirmed in scientific studies. Virgin black seed oil has been shown to have antimicrobial, and antifungal properties, including against antibiotic resistant Staphylococcus Aureus, and H. pylori, the cause of stomach ulcers. It can also act as an analgesic, decreasing pain, an-anticonvulsant in children with apoplexy, a glucose regulator for people with diabetes II, an anti-oxidant with protective actions for many organs, and an anti-histamine helping with symptoms of hay fever. It is also being intensely studied for its actions against cancer cells, especially those of colon or prostate cancer.

Virgin black seed oil contains thymoquinone, which has been identified as its most important bioactive phytochemical, responsible for many of the health benefits of black cumin seeds. The oil contains many other active chemicals, such as nigellone, melanthin, nigilline, demascenine and many different tannins. However, thymoquinone appears to be the chief compound with significant effects on health, and many properties of black seed oil can be replicated by purified thymoquinone.

Black Seed Oil has Anti-Cancer Properties

The most intriguing functions of the thymoquinone in organic virgin black seed oil is its activity against cancer cells. The phytochemical appears to be a potent inhibitor of tumour growth, sometimes leading even to tumour shrinking in tissue culture and in experimental animal models. It appears that there is no single mechanism by which thymoquinone achieves its actions, instead it seems to through several different pathways. Thymoquinone appears to stimulate apoptosis in cancer cells. It also seems to be able to inhibit angiogenesis, the process through which tumours cause the formation of new blood vessels, which are necessary for their growth and metastasis. Although thymoquinone usually functions as an antioxidant, in cancer cells it stimulated reactive oxygen species creation and contributes to oxidative stress, which eventually kills the transformed cells.

Thymoquinone from Black Seed Oil Stimulates Apoptosis in Cancer Cells

Apoptosis, also known as programmed cell death. When apoptosis pathways are activated, a serious of biochemical reactions in the cell causes it to die. Cells in the body, in effect, all carry the programming that causes them to ‘commit suicide’. Although it has to be tightly control, programmed cell death is perfectly natural, it is estimated that tens of billions of cells die through programmed cell death each day in the human body. In fact, when something goes wrong with the pathway, and cells can no longer undergo apoptosis, serious disease results.

One of the functions of apoptosis is to prevent cancer. One of the most important proteins that control this process is the tumour suppressor gene p53. Cancer is the result of DNA damage, which results in mutations in genes, which start dividing uncontrollably. Because DNA damage occurs frequently, each cell has pathways that can sense this damage. These pathways result in increased levels of the protein p53, which arrests the cell during the cell cycle, so it cannot divide. Other proteins then attempt to repair the DNA mutations. If the repair fails, p53 causes the cell to undergo apoptosis, and die, to prevent the daughter cells from inheriting the faulty genes.

Since p53 and apoptosis prevent cells with DNA damage from dividing, they protect the body from developing tumours. However, if the mutation occurs in the p53 gene itself, or other proteins involved in apoptosis, this protection fails, and cancerous cells are able to divide and grow into tumours.

It now appears that thymoquinone can kill cancer cells by stimulating their ability to undergo programmed cell death. It increases the levels of p53 protein, and the related p21/WAF1 protein, while decreasing the level of the Bcl-2 protein, which is anti-apoptotic and hence an oncogene.

Thymoquinone Inhibits Polyp Growth in Familial Adenomatous Polyposis

Thymoquinone was shown to stop tumour growth in a mouse model for familial adenomatous polyposis (FAP), a genetic disease caused by a mutation in the APC gene that often progresses to colorectal cancer. Colorectal cancer is one of the most common types of cancer, accounting for about 8% of total cancer deaths in the world. A research study by a team in Austria showed that thymoquinone treated mice with a mutated APC gene, had fewer colon polyps than control mice. Expression of the c-myc oncogene was also lower in treated mice.

The team concluded that thymoquinone achieved its effects by acting on the wnt/beta-catenin pathway. Wnt is an important pathway in embryonic development, but since it promotes cell proliferation it has tumour-promoting properties in the body if it is deregulated. The APC protein, a product of the gene that is mutated in the familial adenomatous polyposis, is a component of the wnt pathway, it forms part of a ‘destruction complex’. When the wnt signalling molecule is not bound to its receptor. APC forms a complex with axin and GSK, which degrades the signalling molecule beta-catening. When wnt is bound to the receptor, it causes the ‘destruction complex’ to fall apart, beta catenin is not degraded, instead it enters the nucleus where it switches on certain genes, including ones which cause the cell to divide, such as the c-myc oncogene.

The APC gene mutation in the FAP disease, causes an accumulation of beta-catenin in the nucleus, which leads to the increased expression of its target genes, which in turn causes increased cell division and the growth of polyps, which then turn cancerous. The researchers discovered that thymoquinone protects against this by causing beta-catenin to be translocated to the cell membrane rather than the nucleus.

Black Seed Oil Thymoquinone is an HDAC Inhibitor

Another scientific study, conducted by a team from the Thomas Jefferson Center in Philadelphia, discovered that thymoquinone, the bioactive phytochemical in black cumin seed oil, killed about 80% of a human pancreatic cancer cell line, by acting as an HDAC inhibitor. They found that thymoquinone treatment affected the expression of the tumour suppressors p53 and p21 and triggered programmed cell death in the cancer cells.

HDAC inhibitors, act by blocking the enzymes that remove acetyl groups from histones. In the nucleus all the DNA of chromosomes is packaged in chromatin, by being wound around proteins known as histones. Inactive chromatin is densely packed, and genes cannot be accessed by the transcription machinery, and hence cannot be expressed. For a gene to be transcribed, a necessary first step in making the protein the gene is coding for, the tight association between the DNA and the histones has to be loosened, producing open chromatin. One of the mechanisms to achieve that is by acetylating the histone proteins. On the other hand, for genes to become ‘inactive’ and not expressed, enzymes such as histone deacetylases, known as HDACs, must remove the acetyl group. HDAC inhibitors block the action of histone deacetylases.

Although the action of HDAC inhibitors is to activate genes, since they keep histones acetylated, the overall effect is that the expression of only a small number of genes rises, while other genes are repressed. This is due to the complex interplay between different gene products, and also the fact that other proteins, such as transcription factors, can also be acetylated and deacetylated, which affects their activity. The overall result is that HDAC inhibitors seem to have tumour suppressor activities, decreasing the expression of oncogenes, and increasing apoptosis of cancer cells. The fact that thymoquinone acts as an HDAC inhibitor explains part of its anti-cancer activities. For angiogenesis to occur, endothelial cells must migrate into the position of the new capillary, proliferate, invade the tissue, adhere together and form a tube. Many of these steps are controlled by the phosphatidylinositol 3-kinase (AKT) and Raf-MEK-extracellular signal regulated kinase (ERK) pathways. The protein AKT is necessary for the formation and proper functioning of blood vessels. Together with ERK it controls the production of endothelial growth factors. Tests on human umbilical vein endothelial cells show that thymoquinone blocks AKT/ERK activation, and hence angiogenesis.

Thymoquinone from Black Seed Oil Blocks Angiogenesis

An essential step in cancer growth and metastasis is the development of the tumour’s blood vessel system. The growing tumour induces surrounding tissues to undergo, angiogenesis, the growth of new capillaries and their penetration into tissues. Without an adequate blood supply the cancer cells will not get sufficient oxygen and nutrients to allow them to grow. A connection to the body’s blood supply is also often essential for metastasis. Therefore there is much interest in angiogenesis inhibitors as potential anti-cancer drugs. If the growth of new capillaries can be blocked, and the tumour can be deprived of its blood supply, it will not grow and spread.

It seems that thymoquinone from virgin black seed oil can also be helpful in this respect.

Thymoquinone Suppresses Breast Cancer by Acting Through the PPAR Receptors

Thymoquinone has also been shown to inhibit the proliferation of several breast cancer cell lines, such as MCF-7, MDA-MB-231and BT-474. They research study suggested that its target in breast cancer cells are receptors from the PPAR (peroxisome proliferator-activated receptor) family. There are three different PPAR proteins, PPAR-alpha, beta and gamma. They control many important biochemical pathways, such as sugar and lipid metabolism. PPAR-gamma has also been shown to control cell division, differentiation, and apoptosis. It increases the expression of the p21 gene, which in turn controls the expression of p53, and represses the expression of cyclin D1, one fo the proteins essential for the cell cycle. Its overall effect is to cause an arrest in the cell cycle, preventing DNA replication. PPAR-gamma is also thought to control cancer metastasis to other organs and tissues. The study in breast cancer cells showed that thymoquinone activates PPAR-gamma triggering apoptosis in the cells. It also appears to block their migration, which is essential for breast cancer spreading to other tissues.

Thymoquinone also appears to be able to inhibit the growth of doxorubicin resistant breast cancer cells. It seems to be able to upregulate the transcription of the phosphatase and tensin homologue (PTEN) gene. This in turn, blocks the phosphatidylinositol-3-kinase/Akt pathway, which upregulates p53 and p21 expression, resulting in apoptosis of the tumour cells.

Black Seed Oil Thymoquinone Causes Oxidative Stress in Cancer Cells

Researchers at Tulane University in New Orleans discovered another mechanism in which thymoquinone from black cumin seed oil fights cancer. They showed that the phytochemical blocked the growth of several aggressive prostate cancer cell lines by increasing the levels of reactive oxygen species in the tumour cells.

This finding is rather surprising, since thymoquinone is normally an anti-oxidant that protects tissues against oxidative stress. However, in cancer cells its actions appear to be reversed. Thymoquinone appears to have a structure that is similar to that of ubiquinone, which is part of the coenzyme-Q complex in mitochondria. Ubiquinone, also known as co-enzyme Q10, takes part in the electron transport chain that occurs during aerobic respiration in mitochondria, a process that produces free radicals. The scientists, therefore, decided to investigate whether thymoquinone could play a similar role in terms of reactive oxygen species production.

It turns out that thymoquinone, not only induces oxidative stress in prostate cancer cells, but also suppresses the levels of glutathione, a potent anti-oxidant. The result is increased levels of free radicals and reactive oxygen species, which damage the cell and trigger programmed cell death.

Organ Protective Properties of Virgin Black Seed Oil

As well as its amazing anti-cancer properties thymoquinone in black seed oil also has potent anti-oxidative and anti-inflammatory properties. These give it a general anti-cancer activity since free radicals and inflammation are important risk factors for cancer. In addition, the phytochemical also has strong organ-protective action, especially when it comes to the kidneys, liver and lungs. Many studies have shown that thymoquinone treatment protects against the damage caused by reactive oxygen species produced by a variety of toxins.

Free radicals are molecules with an unpaired electron. They are produced as by-products of normal metabolism, especially aerobic respiration in the mitochondria, but also after exposure to air pollution, toxins, or ionizing radiation. Free radicals are very unstable and react to produce reactive oxygen species, which are still unstable and readily oxidise various biochemical such as lipids, proteins, or DNA. The body produces its own antioxidants, such as glutathione, which quench the free radicals and reactive oxygen species to prevent damage to organs and DNA. However, if the free radical damage rises too much, the endogenous anti-oxidant molecules cannot cope and the result is oxidative stress.

In vitro and animal studies show that thymoquinone from black seed oil has potent anti-oxidant and anti-inflammatory properties, and that it can protect tissues from induced oxidative stress. Thymoquinone treatment reduces the levels of oxidation markers in damaged kidneys, liver and lungs. It was also shown to markedly improve glucose metabolism and insulin sensitivity in patients with type II diabetes, but restoring pancreatic-beta cell function.

Thymoquinone Improves the Symptoms of Allergies

The anti-inflammatory and anti-histamine activities of thymoquinone found in black cumin seed oil have raised interest in using it to alleviate the symptoms of allergies. A trial in people affected by hay fever show that it can noticeably reduce many of the symptoms such as nasal congestion, itchy nose, and sneezing. Nestle is trying to obtain a patent for using thymoquinone as an aide in combatting food allergies, based on some novel discoveries Nestle scientists have made about the interactions between the phytochemical and opioid receptors.

Further Reading:

Medicinal actions of thymoquinone

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3642442/

A review of virgin black seed oil thymoquinone anti-tumour activities:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841989/

http://www.molecular-cancer.com/content/12/1/41

http://mct.aacrjournals.org/content/7/7/1789.full

Anti-oxidative and Anti-inflammatory actions of thymoquinone:

http://www.sjkdt.org/article.asp?issn=1319-2442;year=2009;volume=20;issue=5;spage=741;epage=752;aulast=Ragheb

http://www.ncbi.nlm.nih.gov/pubmed/23543440