BLACK CUMIN SEEDS OIL BENEFITS
WRITTEN BY DR. MUHAMMAD MUKTAR, NOTED GOOGLE SCHOLAR
THIS ARTICLE COPYWRITTEN FOR THEPERFECTHEALING.COM ONLY. ALL RIGHTS RESERVED.
THIS ARTICLE COPYWRITTEN FOR THEPERFECTHEALING.COM ONLY. ALL RIGHTS RESERVED.
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Nigella sativa is the scientific name for a plant grown mainly in the South and Southwest Asia. Black seed or black cumin is the common name besides several others like alhabah alsoda, habit albaraka, kalonji, , and the list goes on.
This plant bears beautiful pale blue and white colored flowers. The fruit is in the form of an inflated capsule with several follicles. Each follicle has seeds mainly used as a spice. These seeds are bitter with a pungent odor. Oil extracted from the seeds of this plant has several health benefits. There is ongoing scientific research to identify the composition of Nigella oil and its different constituents having a beneficial impact on human health. A wealth of information exists about the health-promoting benefits of black seed powder or whole seeds. |
Few to worth mention are their usage in controlling various ailments like asthma, diabetes, high blood pressure, sperm function and breast pain (https://www.webmd.com/vitamins/ai/ingredientmono-901/black-seed). This article will summarize significant health benefits of oil extracted from the seeds of Nigella sativa plant. The health benefits of constituents in the oil fraction mainly thymoquinone are also described in this article
Nigella sativa- Historical Perspective
Historically, Nigella seeds and oil have been found in ancient Egyptian excavation, and Pharaoh considered them to be beneficial in the afterlife. The Old Testament book of Isaiah has an official mention of Nigella. Besides its historical use as a spice, the health benefits of this plant have also been described in ancient history.
The real significance of this plant seed was highlighted with the Prophet Muhammad (PBUH) saying “There is healing in black seed (Haba sowda) for all disease except death."
Subsequent upon the Prophet (PBUH) saying the seeds of Nigella received prominent importance as far as the Islamic medicine history is concerned. However, modern drug discovery practices have also proved the benefits of Nigella seeds and oil extracted from them.
The Google Patents search in the last week of October 2018 for the keywords Nigella sativa retrieved 1007 results all describing the health benefits of Nigella and its derivatives proved through modern drug discovery practices (https://patents.google.com/).
It is important to mention here that US Food and Drug Administration, Department of Health and Human Services in the Code of Federal Regulations Title 21 recent release on April 1, 2018, recognize Nigella sativa as a safer product (https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.10).
Historically, Nigella seeds and oil have been found in ancient Egyptian excavation, and Pharaoh considered them to be beneficial in the afterlife. The Old Testament book of Isaiah has an official mention of Nigella. Besides its historical use as a spice, the health benefits of this plant have also been described in ancient history.
The real significance of this plant seed was highlighted with the Prophet Muhammad (PBUH) saying “There is healing in black seed (Haba sowda) for all disease except death."
Subsequent upon the Prophet (PBUH) saying the seeds of Nigella received prominent importance as far as the Islamic medicine history is concerned. However, modern drug discovery practices have also proved the benefits of Nigella seeds and oil extracted from them.
The Google Patents search in the last week of October 2018 for the keywords Nigella sativa retrieved 1007 results all describing the health benefits of Nigella and its derivatives proved through modern drug discovery practices (https://patents.google.com/).
It is important to mention here that US Food and Drug Administration, Department of Health and Human Services in the Code of Federal Regulations Title 21 recent release on April 1, 2018, recognize Nigella sativa as a safer product (https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.10).
Nigella Sativa Seeds Oil
The Nigella seeds are rich in oil contents. A study has reported the oil content of these seeds exceeding 40.37±1.70 g 100 g-1 on dry weight. Proportionally, oil is four times higher than the seeds moisture contents. As such, the seeds are a rich reservoir of oil that can be extracted through various methodologies (1).
Among different oil extraction techniques, the hydraulic press method is preferred. It has been observed that response surface methodology yields higher amounts of oil from black seeds. Constituents wise, Nigella oil is mainly comprised of healthy unsaturated fatty acids that reduce the risk of elevated blood cholesterol besides many health benefits. Several components reported in the oil are thymoquinone (TQ), dithymoquinone (DTQ), thymohydroquinone (THQ), and thymol (THY)(2).
Similarly, other components of the nigella oil are thymol, carvacrol, nigellimine-N-oxide, nigellicine, nigellidine, and alpha-hederin. Thymoquinone has received relatively more attention, and several of its analogs have been prepared for treatment of various ailments. However, one has to keep in mind, that a natural product is always safer when compared with synthetic formulations.
The Nigella seeds are rich in oil contents. A study has reported the oil content of these seeds exceeding 40.37±1.70 g 100 g-1 on dry weight. Proportionally, oil is four times higher than the seeds moisture contents. As such, the seeds are a rich reservoir of oil that can be extracted through various methodologies (1).
Among different oil extraction techniques, the hydraulic press method is preferred. It has been observed that response surface methodology yields higher amounts of oil from black seeds. Constituents wise, Nigella oil is mainly comprised of healthy unsaturated fatty acids that reduce the risk of elevated blood cholesterol besides many health benefits. Several components reported in the oil are thymoquinone (TQ), dithymoquinone (DTQ), thymohydroquinone (THQ), and thymol (THY)(2).
Similarly, other components of the nigella oil are thymol, carvacrol, nigellimine-N-oxide, nigellicine, nigellidine, and alpha-hederin. Thymoquinone has received relatively more attention, and several of its analogs have been prepared for treatment of various ailments. However, one has to keep in mind, that a natural product is always safer when compared with synthetic formulations.
Health Benefits of Nigella (Black Seed) Oil
In describing the health benefits of black seed oil, it is important to mention here that the US FDA certifies the safety of Nigella sativa as a dietary constituent. Moreover, there are several ongoing clinical trials and a vast list of patents associated with various constituents found in the oil. A review of ongoing clinical trials related to thymoquinone component found in the oil fraction of the black seed oil suggest that it is an active agent without any side effects for the treatment of ailments like diabetes, lipid disorders in the body and exert bronchodilator effects.
All this manifest that in the near future there will be the availability of the US, FDA formulations having black seed oil constituent thymoquinone (3). Majority of the world population use traditional medicine which is not approved by the US, FDA and have relatively better efficacy with lesser side effects. Nigella is one such product; however, its safety profile is even approved by the modern dietary ingredients’ evaluation practices also.
Black Seed Oil for the Treatment of Viral Diseases
The black seed oil exerts a potent antiviral effect. Animal studies show that intraperitoneal administration of black seed oil in mice significantly reduced cytomegalovirus infection. The intriguing observation was an augmentation in the number of immune cells like macrophages and T cell that protect mammals from various infectious disease (4).
Administration of Nigella sativa seed oil to patients suffering from hepatitis C virus infections for three months significantly decrease viral infection. Moreover, people who have diabetes and having hepatitis got benefits for both issues, i.e., viral control as well as better control of blood glucose (5).
Intriguingly, adverse drug reactions were minimal suggesting its usage among millions of people who cannot afford very costly treatments for this viral infection.
In describing the health benefits of black seed oil, it is important to mention here that the US FDA certifies the safety of Nigella sativa as a dietary constituent. Moreover, there are several ongoing clinical trials and a vast list of patents associated with various constituents found in the oil. A review of ongoing clinical trials related to thymoquinone component found in the oil fraction of the black seed oil suggest that it is an active agent without any side effects for the treatment of ailments like diabetes, lipid disorders in the body and exert bronchodilator effects.
All this manifest that in the near future there will be the availability of the US, FDA formulations having black seed oil constituent thymoquinone (3). Majority of the world population use traditional medicine which is not approved by the US, FDA and have relatively better efficacy with lesser side effects. Nigella is one such product; however, its safety profile is even approved by the modern dietary ingredients’ evaluation practices also.
Black Seed Oil for the Treatment of Viral Diseases
The black seed oil exerts a potent antiviral effect. Animal studies show that intraperitoneal administration of black seed oil in mice significantly reduced cytomegalovirus infection. The intriguing observation was an augmentation in the number of immune cells like macrophages and T cell that protect mammals from various infectious disease (4).
Administration of Nigella sativa seed oil to patients suffering from hepatitis C virus infections for three months significantly decrease viral infection. Moreover, people who have diabetes and having hepatitis got benefits for both issues, i.e., viral control as well as better control of blood glucose (5).
Intriguingly, adverse drug reactions were minimal suggesting its usage among millions of people who cannot afford very costly treatments for this viral infection.
Black Seed Oil a Potent Analgesic with Antipyretic Effects
Nigella sativa oil possesses strong analgesic and muscle relaxing effect. Since centuries, the oil preparations of the seeds are used to overcome the painful condition and relieving muscular stiffness hindering proper movement of various body parts. Besides empirical pieces of evidence, robust scientific findings prove that Nigella oil is the best preparation without any side effects for the treatment of pain.
The sensation of pain is associated with the nociceptive response system among humans. Oral administration of N. sativa oil (50-400 mg/kg body weight) in the mice model showed a potent suppression of the nociceptive response generating painful sensation (6). As such, usage of oil can be beneficial in several painful conditions among patients, particularly cancer patients.
Nigella sativa oil possesses strong analgesic and muscle relaxing effect. Since centuries, the oil preparations of the seeds are used to overcome the painful condition and relieving muscular stiffness hindering proper movement of various body parts. Besides empirical pieces of evidence, robust scientific findings prove that Nigella oil is the best preparation without any side effects for the treatment of pain.
The sensation of pain is associated with the nociceptive response system among humans. Oral administration of N. sativa oil (50-400 mg/kg body weight) in the mice model showed a potent suppression of the nociceptive response generating painful sensation (6). As such, usage of oil can be beneficial in several painful conditions among patients, particularly cancer patients.
Neuroprotective Effect of Black Seed Oil
Scientific studies prove the neuroprotective effects of black seed oil in the following neurodegenerative disorders:
Thymoquinone a constituent found in black seed oil has beneficial effects in stopping seizures among epileptic individuals. Moreover, the neuroprotection in epileptic mice model is dose-dependent.A study reports that 40 and 80 mg thymoquinone/kg body weight reduced mortality in mice model at the levels of 71.4% and 100% respectively (7).
Studies have also shown that Nigella sativa oil a dietary supplement help in the clearing of malarial parasite to reduce chances of relapse (14). Importantly, several prior studies provide strong empirical evidence that for malarial control nigella is an excellent traditional medicine choice.
Scientific studies prove the neuroprotective effects of black seed oil in the following neurodegenerative disorders:
Thymoquinone a constituent found in black seed oil has beneficial effects in stopping seizures among epileptic individuals. Moreover, the neuroprotection in epileptic mice model is dose-dependent.A study reports that 40 and 80 mg thymoquinone/kg body weight reduced mortality in mice model at the levels of 71.4% and 100% respectively (7).
- Parkinson’s disease
- Spinal injuries
- Depression and mood disorders
- Learning deficits
- Tolerance and dependence
- Brain infections like toxoplasmosis and cerebral malaria
Studies have also shown that Nigella sativa oil a dietary supplement help in the clearing of malarial parasite to reduce chances of relapse (14). Importantly, several prior studies provide strong empirical evidence that for malarial control nigella is an excellent traditional medicine choice.
Black Seed Oil in Cancer Treatment
Nigella sativa oil and thymoquinone mainly present in the oily fraction has shown its efficacy in various types of cancers including leukemia, breast, cervix, liver, kidney, prostate and several others(15). Despite the significant benefits of Nigella, limited scientific studies are touching the molecular aspects related to its curative effects for cancer.
One of the more credible information based on scientific data is its antioxidant effect and enhancement of body immune system. Though it needs to be explored further, however, it makes sense also. Most of the ailments are due to deficient innate defense, and if we strengthen it, cancer can be cured.
A plausible explanation could be the effect of Nigella sativa oil in regulating various biological molecules within the body involved in cancer control through making a strong innate bodily defense. The anticancer effect of thymoquinone present in the black seed oil has been proved through numerous scientific studies (16). Besides thymoquinone, alpha (α)-hederin, another component of the Nigella oil fraction also showed strong anti-cancer effects (17).
The proposed mechanism of cancer control through thymoquinone present in the Nigella sativa oil is the induction of cellular death in cancer tissues. This is through elevating levels of death inducer molecules that kill cancer cells. Besides this antioxidant effect is considered another important factor related to Nigella oil mediated cancer control.
Nigella sativa oil and thymoquinone mainly present in the oily fraction has shown its efficacy in various types of cancers including leukemia, breast, cervix, liver, kidney, prostate and several others(15). Despite the significant benefits of Nigella, limited scientific studies are touching the molecular aspects related to its curative effects for cancer.
One of the more credible information based on scientific data is its antioxidant effect and enhancement of body immune system. Though it needs to be explored further, however, it makes sense also. Most of the ailments are due to deficient innate defense, and if we strengthen it, cancer can be cured.
A plausible explanation could be the effect of Nigella sativa oil in regulating various biological molecules within the body involved in cancer control through making a strong innate bodily defense. The anticancer effect of thymoquinone present in the black seed oil has been proved through numerous scientific studies (16). Besides thymoquinone, alpha (α)-hederin, another component of the Nigella oil fraction also showed strong anti-cancer effects (17).
The proposed mechanism of cancer control through thymoquinone present in the Nigella sativa oil is the induction of cellular death in cancer tissues. This is through elevating levels of death inducer molecules that kill cancer cells. Besides this antioxidant effect is considered another important factor related to Nigella oil mediated cancer control.
Black Seed Oil for Heart Diseases
Thymoquinone present in the oil of black see has demonstrated its cardioprotective effect through several scientific studies. The mechanism involves repairing of damaged cardiomyocytes the heart muscle cells and high anti-oxidant system necessary for reducing inflammatory responses in heart tissues(18).
Black Seeds Oil Protects Gastrointestinal System
The black seed oil is considered an excellent gastroprotective agent. A study in the year 2005 confirmed the existing empirical evidence related to the treatment of gastric ulcer with Nigella oil (19).
Arthritis Control with Black Seed Oil
Arthritis control by using black seed oil is because of thymoquinone present in the oil on reducing interleukin 1 beta (IL-1b) and tumor necrosis factor alpha (TNF-a) that play a major role in the onset of arthritis(20). Several other inflammatory pathways get controlled with black seed oil treatment.
Restoration of Normal Liver Function with Nigella sativa oil
A wealth of scientific literature demonstrates that thymoquinone expert strong hepatoprotective effect. Liver damage is mainly due to enhanced oxidative stress and a multitude of other reactions. Primarily liver damage is assessed through leakage of two aminotransferase enzyme in the serum. Thymoquinone reduces the leakage of these enzymes linked with liver damage suggesting it protects liver damage and repair the injured liver tissues (21).
Diabetes Control with Nigella Oil
Thymoquinone has shown its benefits in both type 1 and type II diabetic disorders. Moreover, the benefits of this component in gestational diabetes have also been reported. Administration of thymoquinone, the oily fraction of Nigella oil, has been reported to enhanced production of insulin necessary for glucose metabolism in diabetic patients as well as recovering the normal function of beta cells involved (22).
Thymoquinone present in the oil of black see has demonstrated its cardioprotective effect through several scientific studies. The mechanism involves repairing of damaged cardiomyocytes the heart muscle cells and high anti-oxidant system necessary for reducing inflammatory responses in heart tissues(18).
Black Seeds Oil Protects Gastrointestinal System
The black seed oil is considered an excellent gastroprotective agent. A study in the year 2005 confirmed the existing empirical evidence related to the treatment of gastric ulcer with Nigella oil (19).
Arthritis Control with Black Seed Oil
Arthritis control by using black seed oil is because of thymoquinone present in the oil on reducing interleukin 1 beta (IL-1b) and tumor necrosis factor alpha (TNF-a) that play a major role in the onset of arthritis(20). Several other inflammatory pathways get controlled with black seed oil treatment.
Restoration of Normal Liver Function with Nigella sativa oil
A wealth of scientific literature demonstrates that thymoquinone expert strong hepatoprotective effect. Liver damage is mainly due to enhanced oxidative stress and a multitude of other reactions. Primarily liver damage is assessed through leakage of two aminotransferase enzyme in the serum. Thymoquinone reduces the leakage of these enzymes linked with liver damage suggesting it protects liver damage and repair the injured liver tissues (21).
Diabetes Control with Nigella Oil
Thymoquinone has shown its benefits in both type 1 and type II diabetic disorders. Moreover, the benefits of this component in gestational diabetes have also been reported. Administration of thymoquinone, the oily fraction of Nigella oil, has been reported to enhanced production of insulin necessary for glucose metabolism in diabetic patients as well as recovering the normal function of beta cells involved (22).
And More and More Ailments Treated
Several other ailments where Nigella oil has shown beneficial effects are respiratory diseases like asthma and dyspnea, restoration of normal kidney functions, and reproductive systems. Muslims across the world believe the benefits of Nigella, however, scientific studies are confirming the Prophet (PBUH) saying.
The significant advantages associated with Nigella sativa oil are due to thymoquinone, though other constituents still need to be explored with modern drug discovery methodologies. The antioxidant and body natural defense boosting property are worth pursuing. Importantly, the product is free from side effects encountered with synthetic medicine.
Strong pre-clinical and empirical data exist as people have been using black seed as herb and traditional medicine since time immemorial.
What is needed is the adoption and validation of this blissful natural remedy through clinical trials. Importantly, due to its safety profile already approved by the US, FDA there is a clear passage for Nigella oil adoption to treat a variety of chronic disorders, infectious disease, and even acute ailments.
Several other ailments where Nigella oil has shown beneficial effects are respiratory diseases like asthma and dyspnea, restoration of normal kidney functions, and reproductive systems. Muslims across the world believe the benefits of Nigella, however, scientific studies are confirming the Prophet (PBUH) saying.
The significant advantages associated with Nigella sativa oil are due to thymoquinone, though other constituents still need to be explored with modern drug discovery methodologies. The antioxidant and body natural defense boosting property are worth pursuing. Importantly, the product is free from side effects encountered with synthetic medicine.
Strong pre-clinical and empirical data exist as people have been using black seed as herb and traditional medicine since time immemorial.
What is needed is the adoption and validation of this blissful natural remedy through clinical trials. Importantly, due to its safety profile already approved by the US, FDA there is a clear passage for Nigella oil adoption to treat a variety of chronic disorders, infectious disease, and even acute ailments.
References
1. Hadjadj N, Acheheb H, Aitchaouche FS, Belhachat D, Ferradji A. Optimization of Oil Extraction from Nigella sativa Seeds by Pressing Using Response Surface Methodology. American Journal of Food Technology 2014;9:136-43.
https://scialert.net/abstract/?doi=ajft.2014.136.143
2. Ghosheh OA, Houdi AA, Crooks PA. High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). J Pharm Biomed Anal 1999;19(5):757-62.
https://www.ncbi.nlm.nih.gov/pubmed/10698539
3. Tavakkoli A, Mahdian V, Razavi BM, Hosseinzadeh H. Review on Clinical Trials of Black Seed (Nigella sativa ) and Its Active Constituent, Thymoquinone. J Pharmacopuncture 2017;20(3):179-93. doi: 10.3831/KPI.2017.20.021.
https://www.ncbi.nlm.nih.gov/pubmed/30087794
4. Salem ML, Hossain MS. Protective effect of black seed oil from Nigella sativa against murine cytomegalovirus infection. Int J Immunopharmacol 2000;22(9):729-40.
https://www.ncbi.nlm.nih.gov/pubmed/10884593
5. Barakat EM, El Wakeel LM, Hagag RS. Effects of Nigella sativa on outcome of hepatitis C in Egypt. World J Gastroenterol 2013;19(16):2529-36. doi: 10.3748/wjg.v19.i16.2529.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646144/
6. Abdel-Fattah AM, Matsumoto K, Watanabe H. Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. Eur J Pharmacol 2000;400(1):89-97.
https://www.ncbi.nlm.nih.gov/pubmed/10913589
7. Hosseinzadeh H, Parvardeh S. Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. Phytomedicine 2004;11(1):56-64. doi: 10.1078/0944-7113-00376.
https://www.ncbi.nlm.nih.gov/pubmed/14971722
8. Sedaghat R, Roghani M, Khalili M. Neuroprotective effect of thymoquinone, the nigella sativa bioactive compound, in 6-hydroxydopamine-induced hemi-parkinsonian rat model. Iran J Pharm Res 2014;13(1):227-34.
https://www.ncbi.nlm.nih.gov/pubmed/24734075
9. Kanter M, Coskun O, Kalayci M, Buyukbas S, Cagavi F. Neuroprotective effects of Nigella sativa on experimental spinal cord injury in rats. Hum Exp Toxicol 2006;25(3):127-33. doi: 10.1191/0960327106ht608oa.
https://www.ncbi.nlm.nih.gov/pubmed/16634331
10. Bin Sayeed MS, Shams T, Fahim Hossain S, Rahman MR, Mostofa A, Fahim Kadir M, Mahmood S, Asaduzzaman M. Nigella sativa L. seeds modulate mood, anxiety, and cognition in healthy adolescent males. J Ethnopharmacol 2014;152(1):156-62. doi: 10.1016/j.jep.2013.12.050. https://www.ncbi.nlm.nih.gov/pubmed/24412554
11. Hosseini M, Mohammadpour T, Karami R, Rajaei Z, Reza Sadeghnia H, Soukhtanloo M. Effects of the hydro-alcoholic extract of Nigella sativa on scopolamine-induced spatial memory impairment in rats and its possible mechanism. Chin J Integr Med 2015;21(6):438-44. doi: 10.1007/s11655-014-1742-5. https://www.ncbi.nlm.nih.gov/pubmed/24584756
12. Adnan LH, Bakar NH, Mohamad N. Opioid dependence and substitution therapy: thymoquinone as potential novel supplement therapy for better outcome for methadone maintenance therapy substitution therapy. Iran J Basic Med Sci 2014;17(12):926-8. https://www.ncbi.nlm.nih.gov/pubmed/25859295
13. Rayan HZ, Heba M, Wagih HM, Atwa MM. Efficacy of Black Seed Oil from Nigella Sativa against Murine Infection with Cysts of Me49 Strain of Toxoplasma gondii. PUJ 2011;4:165-76.
https://pdfs.semanticscholar.org/f726/768226e3d284f2d8ac11ccc814fc525016b2.pdf
14. Emeka PM, Badger-Emeka LI, Eneh CM, Khan TM. Dietary supplementation of chloroquine with nigella sativa seed and oil extracts in the treatment of malaria induced in mice with plasmodium berghei. Pharmacogn Mag 2014;10(Suppl 2): S357-62. doi: 10.4103/0973-1296.133282. https://www.ncbi.nlm.nih.gov/pubmed/24991115
15. Khan MA, Chen HC, Tania M, Zhang DZ. Anticancer activities of Nigella sativa (black cumin). Afr J Tradit Complement Altern Med 2011;8(5 Suppl):226-32. doi: 10.4314/ajtcam.v8i5S.10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252704/
16. Khader M, Bresgen N, Eckl PM. Antimutagenic effects of ethanolic extracts from selected Palestinian medicinal plants. J Ethnopharmacol 2010;127(2):319-24. doi: 10.1016/j.jep.2009.11.001. https://www.ncbi.nlm.nih.gov/pubmed/19913082
17. Swamy SM, Huat BT. Intracellular glutathione depletion and reactive oxygen species generation are important in alpha-hederin-induced apoptosis of P388 cells. Mol Cell Biochem 2003;245(1-2):127-39.
https://www.ncbi.nlm.nih.gov/pubmed/12708752
18. Ojha S, Azimullah S, Mohanraj R, Sharma C, Yasin J, Arya DS, Adem A. Thymoquinone Protects against Myocardial Ischemic Injury by Mitigating Oxidative Stress and Inflammation. Evid Based Complement Alternat Med 2015;2015:143629. doi: 10.1155/2015/143629. https://www.hindawi.com/journals/ecam/2015/143629/
19. Arslan SO, Gelir E, Armutcu F, Coskun O, Gurel A, Sayan H, Celik IL. The protective effect of thymoquinone on ethanol-induced acute gastric damage in the rat. Nutrition Research 2005;25(7):673-80.
https://www.sciencedirect.com/science/article/pii/S0271531705001090
20. Vaillancourt F, Silva P, Shi Q, Fahmi H, Fernandes JC, Benderdour M. Elucidation of molecular mechanisms underlying the protective effects of thymoquinone against rheumatoid arthritis. J Cell Biochem 2011;112(1):107-17. doi: 10.1002/jcb.22884.
https://www.ncbi.nlm.nih.gov/pubmed/20872780
21. Nagi MN, Almakki HA. Thymoquinone supplementation induces quinone reductase and glutathione transferase in mice liver: possible role in protection against chemical carcinogenesis and toxicity. Phytother Res 2009;23(9):1295-8. doi: 10.1002/ptr.2766. https://www.ncbi.nlm.nih.gov/pubmed/19277968
22. Al Wafai RJ. Nigella sativa and thymoquinone suppress cyclooxygenase-2 and oxidative stress in pancreatic tissue of streptozotocin-induced diabetic rats. Pancreas 2013;42(5):841-9. doi: 10.1097/MPA.0b013e318279ac1c.
https://www.ncbi.nlm.nih.gov/pubmed/23429494
1. Hadjadj N, Acheheb H, Aitchaouche FS, Belhachat D, Ferradji A. Optimization of Oil Extraction from Nigella sativa Seeds by Pressing Using Response Surface Methodology. American Journal of Food Technology 2014;9:136-43.
https://scialert.net/abstract/?doi=ajft.2014.136.143
2. Ghosheh OA, Houdi AA, Crooks PA. High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). J Pharm Biomed Anal 1999;19(5):757-62.
https://www.ncbi.nlm.nih.gov/pubmed/10698539
3. Tavakkoli A, Mahdian V, Razavi BM, Hosseinzadeh H. Review on Clinical Trials of Black Seed (Nigella sativa ) and Its Active Constituent, Thymoquinone. J Pharmacopuncture 2017;20(3):179-93. doi: 10.3831/KPI.2017.20.021.
https://www.ncbi.nlm.nih.gov/pubmed/30087794
4. Salem ML, Hossain MS. Protective effect of black seed oil from Nigella sativa against murine cytomegalovirus infection. Int J Immunopharmacol 2000;22(9):729-40.
https://www.ncbi.nlm.nih.gov/pubmed/10884593
5. Barakat EM, El Wakeel LM, Hagag RS. Effects of Nigella sativa on outcome of hepatitis C in Egypt. World J Gastroenterol 2013;19(16):2529-36. doi: 10.3748/wjg.v19.i16.2529.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646144/
6. Abdel-Fattah AM, Matsumoto K, Watanabe H. Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. Eur J Pharmacol 2000;400(1):89-97.
https://www.ncbi.nlm.nih.gov/pubmed/10913589
7. Hosseinzadeh H, Parvardeh S. Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. Phytomedicine 2004;11(1):56-64. doi: 10.1078/0944-7113-00376.
https://www.ncbi.nlm.nih.gov/pubmed/14971722
8. Sedaghat R, Roghani M, Khalili M. Neuroprotective effect of thymoquinone, the nigella sativa bioactive compound, in 6-hydroxydopamine-induced hemi-parkinsonian rat model. Iran J Pharm Res 2014;13(1):227-34.
https://www.ncbi.nlm.nih.gov/pubmed/24734075
9. Kanter M, Coskun O, Kalayci M, Buyukbas S, Cagavi F. Neuroprotective effects of Nigella sativa on experimental spinal cord injury in rats. Hum Exp Toxicol 2006;25(3):127-33. doi: 10.1191/0960327106ht608oa.
https://www.ncbi.nlm.nih.gov/pubmed/16634331
10. Bin Sayeed MS, Shams T, Fahim Hossain S, Rahman MR, Mostofa A, Fahim Kadir M, Mahmood S, Asaduzzaman M. Nigella sativa L. seeds modulate mood, anxiety, and cognition in healthy adolescent males. J Ethnopharmacol 2014;152(1):156-62. doi: 10.1016/j.jep.2013.12.050. https://www.ncbi.nlm.nih.gov/pubmed/24412554
11. Hosseini M, Mohammadpour T, Karami R, Rajaei Z, Reza Sadeghnia H, Soukhtanloo M. Effects of the hydro-alcoholic extract of Nigella sativa on scopolamine-induced spatial memory impairment in rats and its possible mechanism. Chin J Integr Med 2015;21(6):438-44. doi: 10.1007/s11655-014-1742-5. https://www.ncbi.nlm.nih.gov/pubmed/24584756
12. Adnan LH, Bakar NH, Mohamad N. Opioid dependence and substitution therapy: thymoquinone as potential novel supplement therapy for better outcome for methadone maintenance therapy substitution therapy. Iran J Basic Med Sci 2014;17(12):926-8. https://www.ncbi.nlm.nih.gov/pubmed/25859295
13. Rayan HZ, Heba M, Wagih HM, Atwa MM. Efficacy of Black Seed Oil from Nigella Sativa against Murine Infection with Cysts of Me49 Strain of Toxoplasma gondii. PUJ 2011;4:165-76.
https://pdfs.semanticscholar.org/f726/768226e3d284f2d8ac11ccc814fc525016b2.pdf
14. Emeka PM, Badger-Emeka LI, Eneh CM, Khan TM. Dietary supplementation of chloroquine with nigella sativa seed and oil extracts in the treatment of malaria induced in mice with plasmodium berghei. Pharmacogn Mag 2014;10(Suppl 2): S357-62. doi: 10.4103/0973-1296.133282. https://www.ncbi.nlm.nih.gov/pubmed/24991115
15. Khan MA, Chen HC, Tania M, Zhang DZ. Anticancer activities of Nigella sativa (black cumin). Afr J Tradit Complement Altern Med 2011;8(5 Suppl):226-32. doi: 10.4314/ajtcam.v8i5S.10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252704/
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