Nigella sativa / Zwarte komijn / Kalanji

Kalanji is an annual plant with terminal, grayish-blue flowers reaching between 30 and 60 cm in height. The toothed seed pod contains the distinctive tiny (1 to 2 mm long), black, 3-sided seeds that are the plant parts used for medicinal purposes. 1 , 2

History

Kalanji has been used for 3,000 years, with historical records of traditional medicinal use of the seed dating back 2,000 years. Its use began in the Middle East and spread throughout Europe, Africa, and India. Seeds were found in the tomb of King Tutankhamun. Ancient Egyptians believed that medicinal plants such as kalanji played a role in the afterlife. In the first century AD, the Greek physician Dioscorides documented that the seeds were taken for a variety of problems, including headache, toothache, nasal congestion, and intestinal worms. 1 There is a common Islamic belief that kalanji is a remedy for all ailments but that it cannot prevent aging or death. 3

In a survey of plants used in the traditional treatment of hypertension and diabetes in southeastern Morocco, N. sativa was found to be widely used. 4

Chemistry

N. sativa seeds contain fixed oils (36% to 38%), proteins, alkaloids, saponin (melanin), and essential oil (0.4% to 2.5%). 5 The fixed oil is composed mainly of unsaturated fatty acids (linoleic and oleic acids). 6 The major component of the essential oil is thymoquinone (28% to 57%). 3 , 7 Four alkaloids have been isolated: nigellicine and nigellidine (indazoles), and nigellimine and nigellimine N-oxide (isoquinolines). 3 Other constituents include palmitic, glutamic, ascorbic and stearic acids; arginine; methionine; lysine; glycine; leucine; and phytosterols. Crude fiber, calcium, iron, sodium, and potassium are also present. Nutritional composition of the seeds has been determined as 21% protein, 35% carbohydrate, and 36% fat. 1 , 2 , 3 , 8 , 9

Thymoquinone, dithymoquinone (nigellone), thymohydroquinone, and thymol are considered the main active constituents. 10

Kalanji Uses and Pharmacology

Respiratory
At least 2 studies claim that the respiratory effects of kalanji make it beneficial for allergies, cough, bronchitis, emphysema, asthma, flu, and chest congestion. 2 In low concentrations, the constituent nigellone inhibits the release of histamine from mast cells. 11 The essential oil inhibited human neutrophil elastase activity in vitro and could be considered a natural antielastase agent for the treatment of injuries resulting from chronic obstructive pulmonary disease and emphysema. 12

Animal data
The volatile oil of kalanji, with thymoquinone removed, acts as a central respiratory stimulant in guinea pigs. 13

Clinical data
Nigellone suppressed symptoms in the majority of patients when given orally to those suffering from bronchial asthma. 14 In a clinical study, treatment with N. sativa oil in 152 patients with allergic diseases, including rhinitis and bronchial asthma, decreased the IgE and eosinophil count 15 and inhibited 5-lipoxygenase (the main enzyme in leukotriene biosynthesis), 16 supporting the use of N. sativa oil as adjuvant therapy for these conditions.

Antioxidant
The fixed oil and thymoquinone have been shown to inhibit lipid peroxidation. 17 , 18 In addition, compounds isolated from N. sativa have shown free radical scavenging properties. 7 , 19 It appears the compounds in the oil act synergistically; therefore, it is important to use the whole oil or crude extract of the seeds in pharmacological studies. 3 , 10

Animal data
The antioxidant effects of N. sativa have been examined using different hepatic, kidney, and gastric toxicity models in vivo. N. sativa protected against CCl 4 -induced hepatotoxicity. 20 , 21 , 22 In gentamicin-induced toxicity, treatment with N. sativa oil produced dose-dependent amelioration of the biochemical and histological indices of nephrotoxicity. 23 , 24 Pretreatment with N. sativa in rats undergoing ethanol-induced gastric ulcer caused an increase in glutathione level, mucin content, and free acidity compared with controls. 25 Accordingly, a potential benefit of N. sativa seeds is the reduction of toxicity from anti-cancer drugs or from environmental or infectious factors because of its antioxidant properties. 10

Immune system
Kalanji enhances production of human interleukin and alters macrophages in vitro, suggesting an enhanced immune response. 26 Studies in the last decades suggest that ongoing use of N. sativa can enhance immune responses in humans. 10 The majority of subjects treated with N. sativa oil for 4 weeks showed a 53% increase in CD 4 to CD 8 T cells ratio and a 30% increase in natural killer cell function. 27

In contrast to this enhancing effect on T cell-mediated immune response, N. sativa constituents have shown a tendency to down regulate B cell-mediated immunity. 27 , 28 In one study, treatment with N. sativa oil induced a 2-fold decrease in antibody production in response to typhoid vaccination as compared with control rats. 29 Accordingly, it is likely that N. sativa may enhance cellular immunity but suppress humoral immunity. 10 However, further studies are required to validate this hypothesis.

Cancer
In vitro and in vivo studies indicate that the oil and the active constituents of N. sativa seeds possess anti-tumor effects. 10 , 29 , 30 , 31 Thymoquinone protected against induced hepatotoxicity in mice in vivo 20 and in rat hepatocytes. 23 A mixture containing kalanji seeds was protective against diethylnitrosamine-mediated carcinogenic changes in rat liver. 32 The constituents thymoquinone and alpha-hederin have demonstrated cytotoxic actions in human cell lines as well. 33

Animal data
Kalanji has inhibited stomach tumors in mice. 34 Topical application of kalanji and saffron delayed and reduced papilloma formations in mice. 35

Clinical data
There are no clinical data regarding the use of kalanji for cancer.

Anti-inflammatory and analgesia
Traditional use of kalanji as a poultice of ground seeds for inflammatory ailments such as rheumatism, headache, and certain skin conditions is supported by modern studies. A fixed oil preparation demonstrated anti-eicosanoid and antioxidant activity, supporting the seeds' use for anti-inflammatory actions. 17 Thymoquinone is a potent inhibitor of thromboxane B 2 and leukotriene B 2 through the inhibition of cyclooxygenase and lipoxygenase, respectively. 17 , 36

Animal data
Research in mice using various models of analgesia concluded that N. sativa oil has strong antinociceptive actions. 37 , 38 , 39 , 40 In addition, it is likely that N. sativa polyphenols are particularly beneficial in alleviating pain of inflammatory origin. 39 In another study, the effects of thymoquinone on acetic acid-induced colitis in rats showed that pretreatment for 3 days led to complete protection against colitis with a comparable effect to sulfasalazine. 41 It has long been observed that N. sativa oil has anti-inflammatory and analgesic properties: systemic and local administration of black cumin seed essential oil resulted in potent analgesic and anti-inflammatory effects in mice. 40 In another study in rats with induced arthritis, oral thymoquinone suppressed the markers of arthritis both clinically and radiologically. 42

Clinical data
There are no clinical data regarding the use of kalanji for inflammatory or pain states.

Antidiabetic
In a recent survey of plants used in the traditional treatment of hypertension and diabetes in southeastern Morocco, N. sativa was the plant most frequently used by medical herbalists and others. 3

Animal data
Treatment of streptozotocin-induced diabetic rats with N. sativa caused a decrease in elevated serum glucose, an increase in serum insulin concentrations, and partial regeneration or proliferation of pancreatic beta cells, causing an increase in insulin secretion. 31 , 43 , 44 , 45 , 46 , 47 In another study, N. sativa treatment of diabetic rats increased the area of insulin immunoreactive beta-cells, suggesting that N. sativa might be used as a safe and effective therapy for diabetes. 48

Clinical data
There are no clinical data regarding the use of kalanji for diabetic ailments.

Antihypertensive
In a survey of plants used in the traditional treatment of hypertension and diabetes in southeastern Morocco, N. sativa was the plant most frequently used by medical herbalists and others. 3

Animal data
Kalanji may decrease arterial blood pressure in rats, suggesting its use as an antihypertensive agent. 49 Thymoquinone is effective in protecting rats against N-nitro-L-arginine methyl ester (L-NAME)-induced hypertension and renal damage, perhaps via antioxidant activity. 50 It reduced the increase in systolic blood pressure induced by L-NAME in a dose-dependent manner. 50

Clinical data
There are no clinical data regarding the use of kalanji for hypertension.

Antimicrobial/Antiparasitic
Kalanji traditionally has been used for conjunctivitis, 2 abscesses, parasites, and other infections. The essential oil of the seed has been reported as an effective antibacterial, antifungal, antiviral, and anthelmintic agent. 51 , 52 , 53 , 54 , 55

Animal data
Kalanji has eradicated staphylococcal infections in mice and has also displayed other gram-negative and gram-positive antibacterial actions, some of which are synergistic with other antibiotics. 52

An aqueous extract of N. sativa seeds inhibited the growth of Candida albicans when inoculated into mice. 54 In vitro, the extract and its active constituent, thymoquinone, inhibited 8 clinical isolates of common dermatophytes. 53

In vivo treatment with N. sativa oil induced a striking antiviral effect against murine cytomegalovirus infection. 55

Other studies have revealed N. sativa essential oil's antischistome effects 56 and antihelmintic activity against tapeworms, nematodes, and cestodes. 57 , 58

Clinical data
There are no clinical data regarding the use of kalanji as an antimicrobial or antiparasitic agent.

Miscellaneous uses
Kalanji eases gas and colic. 1 It has also been used for diarrhea, dysentery, constipation, and hemorrhoids. 2
Kalanji also plays a role in women's health, stimulating menstruation and increasing milk flow. 1 One study reports kalanji to have an anti-oxytocic potential in rat uterine smooth muscle, inhibiting spontaneous contractions. 59 Another report discusses the use of a seed extract to prevent pregnancy in rats 1 to 10 days postcoitum. 60
Kalanji has also been used as a flavoring or as a spice.

Dosage
There are no clinical data for kalanji upon which to base dosing recommendations in humans.

Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions
None well documented.

Adverse Reactions
There are at least 2 case reports of allergic contact dermatitis from topical use of the oil. 61 , 62 The seed extract and its constituents are characterized by a very low degree of toxicity/adverse reactions. 3

Toxicology
While very few studies have addressed the possible toxicity of N. sativa seeds and its constituents, no major toxicities have been reported. 10 Further studies are required.

Bibliography
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17. Houghton PJ, Zarka R, de las Heras B, Hoult JR. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Med . 1995 ; 61 ( 1 ): 33-36 .
18. Hosseinzadeh H, Parvardeh S, Asl MN, Sadeghnia HR, Ziaee T. Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperfusion injury in rat hippocampus. Phytomedicine . 2007 ; 14 ( 9 ): 621-627 .
19. Badary OA, Taha RA, Gamal El-Din AM, Abdel-Wahab MH. Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol . 2003 ; 26 ( 2 ): 87-98 .
20. Nagi M, et al. Thymoquinone protects against carbon tetrachloride hepatotoxicity in mice via an antioxidant mechanism. Biochem Mol Biol Int . 1999 ; 47 ( 1 ): 153-159 .
21. Al-Ghamdi MS. Protective effect of Nigella sativa seeds against carbon tetrachloride-induced liver damage. Am J Chin Med . 2003 ; 31 ( 5 ): 721-728 .
22. Kanter M, Coskun O, Budancamanak M. Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World J Gastroenterol . 2005 ; 11 ( 42 ): 6684-6688 .
23. Daba M, Abdel-Rahman MS. Hepatoprotective activity of thymoquinone in isolated rat hepatocytes. Toxicol Lett . 1998 ; 95 ( 1 ): 23-29 .
24. Ali BH. The effect of Nigella sativa oil on gentamicin nephrotoxicity in rats. Am J Chin Med . 2004 ; 32 ( 1 ): 49-55 .
25. El-Dakhakhny M, Barakat M, El-Halim MA, Aly SM. Effects of Nigella sativa oil on gastric secretion and ethanol induced ulcer in rats. J Ethnopharmacol . 2000 ; 72 (1–2): 299-304 .
26. Haq A, Abdullatif M, Lobo PI, Khabar KS, Sheth KV, al-Sedairy ST. Nigella sativa : effect on human lymphocytes and polymorphonuclear leukocyte phagocytic activity. Immunopharmacology . 1995 ; 30 ( 2 ): 147-155 .
27. El-Kadi A, et al. 1st International Conference on Scientific Miracles of Quran and Sunnah, Islamabad, Pakistan.
28. Swamy SM, Tan BK. Cytotoxic and immunopotentiating effects of ethanolic extract of Nigella sativa L. seeds. J Ethnopharmacol . 2000 ; 70 : 1-7 .
29. Islam SN, Begum P, Ahsan T, Huque S, Ahsan M. Immunosuppressive and cytotoxic properties of Nigella sativa . Phytother Res . 2004 ; 18 ( 5 ): 395-398 .
30. Salomi NJ, Nair SC, Jayawardhanan KK, Varghese CD, Panikkar KR. Antitumour principles from Nigella sativa seeds. Cancer Lett . 1992 ; 63 ( 1 ): 41-46 .
31. al-Awadi F, Gumaa KA. Studies on the activity of individual plants of an antidiabetic plant mixture. Acta Diabetol Lat . 1987 ; 24 ( 1 ): 37-41 .
32. Iddamaldeniya SS, Thabrew MI, Wickramasinghe SM, Ratnatunge N, Thammitiyagodage MG. A long-term investigation of the anti-hepatocarcinogenic potential of an indigenous medicine comprised of Nigella sativa , Hemidesmus indicus and Smilax glabra . J Carcinog . 2006 ; 5 : 11-16 .
33. Worthen D, Ghosheh OA, Crooks PA. The in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa L. Anticancer Res . 1998 ; 18 ( 3A ): 1527-1532 .
34. Badary O, Al-Shabanah OA, Nagi MN, Al-Rikabi AC, Elmazar MM. Inhibition of benzo(a)pyrene-induced forestomach carcinogenesis in mice by thymoquinone. Eur J Cancer Prev . 1999 ; 8 ( 5 ): 435-440 .
35. Salomi MJ, Nair SC, Panikkar KR. Inhibitory effects of Nigella sativa and saffron ( Crocus sativus ) on chemical carcinogenesis in mice. Nutr Cancer . 1991 ; 16 ( 1 ): 67-72 .
36. El-Dakhakhny M, Madi NJ, Lembert N, Ammon HP. Nigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5–lipoxygenase products in polymorphonuclear leukocytes in rats. J Ethnopharmacol . 2002 ; 81 (2): 161-164 .
37. Khanna T, et al. CNS and analgesic studies on Nigella sativa . Fitoterapia . 1993 ; 5 : 407-410 .
38. Abdel-Fattah M, Matsumoto K, Watanabe H. Antinociceptive effects of Nigella sativa oil and its major components in mice. Eur J Pharmacol . 2000 ; 400 : 89-97 .
39. Ghannadi A, Hajhashemi V, Jafarabadi H. An investigation of the analgesic and anti-inflammatoty effects of Nigella sativa seed polyphenols. J Med Food . 2005 ; 8 ( 4 ): 488-493 .
40. Hajhashemi V, Ghannadi A, Jafarabadi H. Black cumin seed essential oil, as a potent analgesic and anti-inflammatory drug. Phytother Res . 2004 ; 18 ( 5 ): 195–199 .
41. Mahgoub AA. Thymoquinone protects against experimental colitis in rats. Toxicol Lett . 2003 ; 143 : 133-143 .
42. Tekeoglu I, Dogan A, Demiralp L. Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat models. Phytother Res . 2006 ; 20 : 869-871 .
43. al-Awadi F, Fatania H, Shamte U. The effect of a plants mixture extract on liver gluconeogenesis in streptozotocin induced diabetic rats. Diabetes Res . 1991 ; 18 ( 4 ): 163-168 .
44. Kanter M, Meral I, Yener Z, Ozbek H, Demir H. Partial regeneration/proliferation of the beta-cells in the islets of Langerhans by Nigella sativa L. in streptozotocin-induced diabetic rats. Tokohu J Exp Med . 2003 ; 201 ( 4 ): 213-219 .
45. Kanter M, Coskun O, Korkmaz A, Oter S. Effects of Nigella sativa on oxidative stress and beta-cell damage in streptozotocin-induced diabetic rats. Anat Rec A Discov Mol Cell Evol Biol . 2004 ; 279 ( 1 ): 685-691 .
46. Rchid H, Chevassus H, Nmila R, et al. Nigella sativa seed extracts enhance glucose-induced insulin release form rat-isolated Langerhans islets. Fundam Clin Pharmacol . 2004 ; 18 ( 5 ): 525-529 .
47. Hawsawi ZA, Ali BA, Bamosa AO. Effect of Nigella sativa (black seed) and thymoquinone on blood glucose in albino rats. Ann Saudi Med . 2001 ; 21 ( 3-4 ): 242-244 .
48. Altan MF, Kanter M, Donmez S, Kartal ME, Buyukbas S. Combination therapy of Nigella sativa and human parathyroid hormone on bone mass, biochemical behaviour and structure in streptozotocin-induced diabetic rats. Acta Histochem . 2007 ; 109 ( 4 ): 304-314 .
49. el Tahir KE, Ashour MM, al-Harbi MM. The cardiovascular actions of the volatile oil of the black seed ( Nigella sativa ) in rats: elucidation of the mechanism of action. Gen Pharmacol . 1993 ; 24 ( 5 ): 1123-1131 .
50. Khattab MM, Nagi MN. Thymoquinone supplementation attenuates hypertension and renal damage in nitric oxide deficient hypertensive rats. Phytother Res . 2007 ; 21 ( 5 ): 410-414 .
51. Agarwal R, Kharya MD, Shrivastava R. Antimicrobial & anthelmintic activities of the essential oil of Nigella sativa Linn. Indian J Exp Biol . 1979 ; 17 ( 11 ): 1264-1265 .
52. Hanafy M, Hatem ME. Studies on the antimicrobial activity of Nigella sativa seed (black cumin). J Ethnopharmacol . 1991 ; 34 ( 2-3 ): 275-278 .
53. Aljabre SH, Randhawa MA, Akhtar N, Alakloby OM, Alqurashi AM, Aldossary A. Antidermatophyte activity of ether extract of Nigella sativa and its active principle, thymoquinone. J Ethnopharmacol . 2005 ; 101 ( 1-3 ): 116-119 .
54. Khan MA, Ashfaq MK, Zuberi HS, Mahmood MS, Gilani AH. The in vivo antifungal activity of aqueous extract from Nigella sativa seeds. Phytother Res . 2003 ; 17 ( 2 ): 183-186 .
55. Salem ML, Hossain MS. Protective effect of black seed oil from Nigella sativa against murine cytomegalovirus infection. Int J Immunopharmacol . 2000 ; 22 ( 9 ): 729-740 .
56. Mahmoud MR, El-Abhar HS, Saleh S. The effect of Nigella sativa oil against the liver damage induced by Schistosoma mansoni infection in mice. J Ethnopharmacol . 2002 ; 79 ( 1 ): 1-11 .
57. Agarwal R, Kharya MD, Shrivastava R. Antimicrobial & anthelmintic activities of the essential oil of Nigella sativa Linn. Indian J Exp Biol . 1979 ; 17 ( 11 ): 1264-1265 .
58. Akhter MS, Riffat S. Field trial of Saussurea lappa roots against nematodes and Nigella sativa seed against cestodes in children. J Pak Med Assoc . 1991 ; 41 ( 8 ): 185-187 .
59. Aqel M, Shaheen R. Effects of the volatile oil of Nigella sativa seeds on the uterine smooth muscle of rat and guinea pig. J Ethnopharmacol . 1996 ; 52 ( 1 ): 23-26 .
60. Keshri G, Singh MM, Lakshmi V, Kamboj VP. Post-coital contraceptive efficacy of the seeds of Nigella sativa in rats. Indian J Physiol Pharmacol . 1995 ; 39 ( 1 ): 59-62 .
61. Zedlitz S, Kaufmann R, Boehncke WH. Allergic contact dermatitis from black cumin ( Nigella sativa ) oil-containing ointment. Contact Dermatitis . 2002 ; 46 ( 8 ): 188 .
62. Steinmann A, Schätzle M, Agathos M, Breit R. Allergic contact dermatitis from black cumin ( Nigella sativa ) oil after topical use. Contact Dermatitis . 1997 ; 36 ( 5 ): 268-269 .



Nigella sativa, een plantaardige insulinevervanger

Een hele beschaafde dosis Nigella sativa - in het Midden-Oosten beter bekend als Habbat ul Baraka of Habbat ul Sauda, bij ons heet het zwarte komijn, laat het lichaam meer insuline aanmaken en verhoogt tegelijkertijd in de spieren de gevoeligheid voor insuline. Dat schrijven Marokkaanse en Canadese onderzoekers in Evidence-Based Complementary and Alternative Medicine. Als je hun dierstudie leest, dan krijg je een vermoeden dat Nigella sativa wellicht een razend interessant supplement is voor iedereen die spieren wil opbouwen en tegelijkertijd lichaamsvet wil verliezen.

Studie: Nigella sativa, een plantaardige insulinevervanger
De onderzoekers experimenteerden gedurende vier weken met een soort woestijnrat - Meriones shawi - waarvan een deel gezond was, en waarvan een deel onvoldoende insuline produceerde. Een deel van de diabete woestijnratten kreeg elke dag het diabetesmedicijn metformin toegediend, een ander deel een extract van de zaden van Nigella sativa.
De onderzoekers maakten hun extracten zelf. Ze gebruikten gedroogde en gemalen zaden uit Marokko, en haalden daar met ethanol de actieve stoffen uit. Het humane equivalent van de dosis die ze toedienden aan hun woestijnratten was ongeveer 400-700 milligram per dag. Neem je geen extracten, maar gedroogde zaden, dan kom je uit op ongeveer 20-25 gram poeder per dag


Een hele beschaafde dosis Nigella sativa - in het Midden-Oosten beter bekend als Habbat ul Baraka of Habbat ul Sauda, in deze contreien heet het zwarte komijn - laat het lichaam meer insuline aanmaken en verhoogt tegelijkertijd in de spieren de gevoeligheid voor insuline. Dat schrijven Marokkaanse en Canadese onderzoekers in Evidence-Based Complementary and Alternative Medicine. Als je hun dierstudie leest, dan krijg je een donkerbruin vermoeden dat Nigella sativa wellicht een razend interessant supplement is voor iedereen die spieren wil opbouwen en tegelijkertijd lichaamsvet wil verliezen.
Resultaten
Toen de onderzoekers na vier weken de proefdieren een partij glucose toedienden, zagen ze dat in de diabete dieren die Nigella sativa hadden gekregen de glucosespiegel sneller normaliseerden dan in de diabete dieren die geen Nigella sativa hadden gekregen.
Nigella sativa verhoogde de concentratie van 'het goede cholesterol' HDL, en verlaagde de concentratie triglyceriden. Dat impliceert dat het extract de kans op hart- en vaataandoeningen vermindert.
De toediening van Nigella sativa verhoogde de insulinespiegel. Tegelijkertijd verhoogde het extract in de spiercellen de activiteit van het glucosetransporteiwit GLUT4. De spieren werden dus gevoeliger voor insuline, en namen meer voedingsstoffen op uit het bloed.

Conclusie
"Nigelle sativa extract greatly improves systemic glucose homeostasis and HDL-cholesterol in diabetic Meriones shawi by acting through several mechanisms", resumeren de onderzoekers. "Most importantly, Nigella sativa increases circulating insulin and enhances the sensitivity of peripheral tissues to the hormone. The latter effect can be attributed in part to an activation of the AMPK pathway in skeletal muscle and liver and to an increased content of Glut4 in skeletal muscle."
"Such pleiotropic actions provide strong evidence in support of the traditional use of Nigella sativa seeds for the treatment of diabetes. They further call for high-quality clinical studies to determine the optimal conditions for complementary or alternative treatment in diabetic patients."

Bron:
Evid Based Complement Alternat Med. 2011;2011:538671.



Nigella / Nigella sativa
Family: Ranunculaceae 
by Gayle Engels, Josef Brinckmann
HerbalGram. 2017; American Botanical Council

The genus Nigella is relatively small and contains about 18 species with several sub-species1 and numerous genotypes.2 All Nigella species are therophytes: annuals that complete their life cycle in a short favorable period and survive harsh periods as seeds.3 Nigella sativa, perhaps the most well-known member of the genus, grows 8-35 inches (20-90 cm) in height and has finely divided, somewhat threadlike leaves. This species has pale-blue to pale-purple flowers that bloom in the spring and produce seed capsules (fruit) that contain numerous black seeds.4

The genus likely originated in parts of the eastern Mediterranean, northeastern Africa, and southwestern Asian regions.5,6 Nigella sativa is found growing wild in regions of northern Africa,7 Turkey, Syria, Iraq,8 and Iran.9 The species is also cultivated on a commercial scale in northern Africa (Egypt,10 Tunisia,11 Sudan12), eastern Africa (Ethiopia13,14), western Asia (Iraq,11 Israel,15 Jordan,16 Lebanon,17 Syria,18 Turkey,10 Yemen19), and southern Asia (India,20 Iran,21 Pakistan22).

The majority of the global commercial supply of N. sativa seed is obtained from cultivation in Egypt, Turkey,18 and India.12 In India, it is mainly grown in the far northern states of Punjab, Himachal Pradesh, Bihar, and Assam.23 Also cultivated extensively in Iran,24 N. sativa is traditionally farmed by communities situated in the provinces of Fars, Khorasan, and Qazvin.21 Most of the certified organic N. sativa seed in the global market originates from farms in Egypt’s El-Fayoum agricultural area in the Nile Valley,10 although there is some organic production in Turkey and India. It should be noted that in Turkey many farmers plant the seeds of N. damascena in the same fields with N. sativa (email from K. Hüsnü Can Başer, April 5, 2017).

HISTORY AND CULTURAL SIGNIFICANCE

The common name and genus name Nigella is derived from the Latin niger, meaning “black.” The term nigellus is a derivative that means “blackish” or “dark.” The species name sativa, meaning “cultivated,”25 is not surprising given that N. sativa had been cultivated for thousands of years before Swedish botanist Carl Linnaeus named it in 1753.26

In the United States, the preferred standardized common name for N. sativa is simply “nigella,” according to the second edition of the American Herbal Products Association’s Herbs of Commerce.27 Nigella sativa is also known as black cumin, black caraway,28 and black seed,8 although the common names “cumin” and “caraway” may be misleading, as these names refer to common spice plants (Cuminum cyminum and Carum carvi, respectively) in the carrot, or Apiaceae, family. One of N. sativa’s main trade names, kalonji, is also the name used in the Arabic Unani-Tibb system of medicine.29

Several archeological sites in Egypt provide evidence of human use of N. sativa seed from 1324 BCE through the time of the annexation of Egypt by the Romans in 30 BCE.30 There is also evidence of cultivation, culinary use, and medicinal use in Mesopotamia from the late third millennium BCE until the late first millennium BCE.5 Cuneiform tablets of ancient Assyria (comprising parts of present-day Iraq, Iran, Syria, and Turkey) describe various uses for N. sativa, including for cases of “a ghost lying on the patient,” which called for fumigation with a preparation made from 10 shekels (approximately 110 g) of nigella seed.31 Believed at the time to be useful for the afterlife journey, nigella seeds were placed in the tomb of Egyptian pharaoh Tutankhamun (ca. 1332-1324 BCE).2 At the ancient Anatolian Boyalı Höyük archeological site, in the present-day Turkish province of Çorum, a pilgrim’s flask (ampulla) from ca. 1650 BCE (the Old Hittite Period) was found to contain a cache of N. sativa seeds mixed with bee propolis and beeswax. While N. sativa seeds are traditionally taken with bee products in this region, this may be the first archeological evidence of the combination.32 There is also evidence of Levantine-Aegean trade in N. sativa seed during the Late Bronze Age. Excavations of the Uluburun shipwreck, which occurred sometime between 1350 BCE and 1300 BCE off the Mediterranean coast of present-day Turkey, uncovered N. sativa seeds contained in Canaanite amphorae (tall, narrow-necked jars with handles).33 The use of nigella seed was described in the Book of Isaiah 28:25-27 of the Hebrew Bible as well, which dates back to the eighth century BCE.15

In his De Materia Medica, Greek pharmaco-botanist Dioscorides (40-90 CE) described the black seeds of a plant he called melanthion (now believed to have been N. sativa) for use as food (sprinkled on bread) or as a treatment for difficult breathing (when drunk with soda), headaches (applied to forehead), toothaches (boiled with vinegar and pitch pine; used as mouth wash), imperfections of the skin, leprosy (applied with vinegar), incipient cataracts (applied in the nostril as an unguent [an ointment or lubricant] made from iris [Iris spp., Iridaceae]), and catarrh (as nasal inhalant). Dioscorides also described the use of melanthion to remove corns (applied with old urine to incised corns), expel roundworms (applied by smearing with water), stimulate menstruation and urination, and repel snakes (fumigation).34 Fragments of cultivated plant remains of N. sativa (both carbonized and desiccated seeds) have been identified at archeological sites in the eastern desert of Egypt, Mons Claudianus,35 a Roman quarry settlement inhabited during the late first and second centuries, and Mons Porphyrites, another Roman mining site.36 During the same period, Romans brought nigella seed with them to western European outposts. Excavation of the second century Roman settlement of Oedenburg (in the lower plains of the Rhine River in Germany) turned up mineralized seeds of N. sativa — a rare archeological finding that indicates N. sativa seed was important enough to be imported from the Mediterranean.37,38

Nigella seed is widely used in the traditional Ayurvedic,23 Siddha,39 and Unani29 systems of medicine, as well as in oral-tradition folk and tribal medicines of India.40 It is also used in traditional Arabic and Islamic medicine (TAIM),41 Iranian traditional medicine (ITM),42 and traditional Sudanese medicine,43 among other systems of medicine. Medicinal uses of nigella seed (Arabic name: hubatul-sudda) were also described in the hadith literature, attributed to the Islamic Prophet Muhammad and compiled during the eighth and ninth centuries.44 A claim that nigella seed is a medicine for every disease except death has been attributed to the Prophet Muhammad.13,45 In TAIM practice, both the seed (taken with honey) and the fatty oil are used for treating a range of intestinal disorders and respiratory tract conditions.41 In ITM, nigella seed (Persian names: shoneez, currently siahdaneh) is used in some herbal preparations to treat epilepsy.46

Nigella sativa is still widely used in Asian systems of medicine. As such, quality standards monographs providing specifications and test methods for N. sativa seed have been published in the Ayurvedic Pharmacopoeia of India,23 Siddha Pharmacopoeia of India,39 and in the Unani Pharmacopoeia of India.29 The United States Pharmacopeial Convention proposed the development of a “Nigella Sativa Seed” monograph for its Herbal Medicines Compendium in May 2013. A draft version of that monograph is posted online with a call for submission of validated information needed to complete the monograph.47 India’s Ministry of Agriculture also has established national grade designations and quality standards for the dried, whole, mature seeds of N. sativa (Hindi name: kalonji), as well as for the powdered seed for use as a spice. Among other specification requirements, “special grade” kalonji seed must contain minimum 1.5% (v/w) essential oil while “standard grade” kalonji must contain minimum 1.0% (v/w) essential oil.48 In 2014, India, through the Codex Alimentarius Committee on Spices and Herbs, proposed the development of an international codex standard for cumin, including both N. sativa and brown cumin (Cuminum cyminum), with a goal to finalize it by July 2017.49

CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES

In countries where the Ayurvedic system of medicine is recognized and practiced (e.g., India, Bangladesh, Bhutan, Malaysia, Nepal, and Sri Lanka), the powdered dried seed of N. sativa, referred to as upakuncika in Sanskrit, is used as a component of preparations for treating abdominal distention with gas, gaseous tumor of the abdomen, diarrhea, and worm infestation.23 Where the Unani system of medicine is recognized and practiced (e.g., Bangladesh, India, Malaysia, Pakistan, and Sri Lanka), the dried seed is used as a component of medicinal formulations to treat asthma, colic, flatulence, weakness of the stomach, hemicrania continua (persistent unilateral headache) and migraine, arthralgia (joint pain), lumbago (lower back pain), hemiplegia (paralysis of one side of the body), Bell’s palsy (paralysis on one side of the face), jaundice, pityriasis (patches on skin), and leukoderma/vitiligo (loss of skin pigmentation). Kalonji is often dispensed as a component of compound Unani medicines known as majoon or halwa. These soft or semi-solid preparations are made with powdered botanicals and mixed with honey, resulting in a consistency like that of the popular confection halva.29 In Siddha medicine — a Dravidian system of medicine originating in the southeastern Indian state of Tamil Nadu, now also practiced in the neighboring states of Karnataka, Kerala, and Andhra Pradesh, as well as in parts of Malaysia, Singapore, and Sri Lanka — the dried seed, referred to as karuncirakam in Tamil, is used as a component of formulations indicated for treatment of conditions including painful gastrointestinal disorders with indigestion, flatulence, jaundice, scalp eczema, scabies, and skin ulcers.39

In the United States, the Food and Drug Administration (FDA) classifies “black cumin (black caraway), Nigella sativa L.” as Generally Recognized as Safe (GRAS) for use as a spice, natural seasoning, or flavoring.28 Nigella is also permitted as a component of dietary supplement products, which require FDA notification within 30 days of marketing if a structure-function claim is made and product manufacturing that conforms with dietary supplement current Good Manufacturing Practices (cGMPs).50

In Canada, both N. sativa seed and seed oil are regulated as medicinal ingredients of licensed natural health products (NHPs, a category of drugs), which require pre-marketing authorization from the Natural and Non-prescription Health Products Directorate. At the time of this writing (April 2017), there were 85 licensed NHPs that list some form of N. sativa as an ingredient, of which 78 list it as a medicinal ingredient and seven as a non-medicinal ingredient.51

For use in cosmetic products, the European Commission Health and Consumers Directorate lists “Nigella Sativa Seed Extract” for perfuming and skin-conditioning functions, and “Nigella Sativa Seed Oil” (fixed oil expressed from the seeds of N. sativa) for emollient, perfuming, and skin-conditioning functions.52

MODERN RESEARCH

There is significant genetic variation and quantifiable differences in chemical and nutrient composition among N. sativa seed chemotypes of Egyptian, Iranian, Syrian, and Turkish origin.53 Such differences may also exist in chemotypes found within a single country. In India, for example, samples of N. sativa seed obtained from 10 different states showed significant variation in chemical constituents and morphology.54

The primary constituents in N. sativa seed are fatty oils (30-35%), mainly glycerol esters of linoleic, oleic, and palmitic acids, and aliphatic hydrocarbons, arachidonic acid (0.01-0.4%), -linolenic acid (0.1-1%), and tocopherols (about 170 mg/kg). The seed also contains essential oil (0.4-2.5%), which is composed mainly of monoterpenes, including -cymene, thymoquinone, -pinene, and carvacrol. The chemical nature of the constituents nigellone and nigellin remains unclear. Nigellone, described as a component of the essential oil, is possibly a polymer of thymoquinone, while nigellin has been described as an alkaloid. There are also traces of isoquinoline alkaloids (nigellicine and nigellimin-N-oxide), an indazole-type alkaloid (nigellidine-4-O-sulfite), and dolabellane-type diterpene alkaloids (nigellamines A1 to A5, B1, B2, and C).55 Analysis of essential oil composition can distinguish N. sativa and N. damascena. The essential oil of N. damascena, which is used in perfumery, contains approximately 8-10% of damascenine, a blue-fluorescing alkaloid. Nigella sativa essential oil does not contain this compound and therefore shows no fluorescence (email from K. Hüsnü Can Başer, April 5, 2017).

In vivo and in vitro studies have shown nigella seed powder and oil to have antibacterial, antifungal, antihistaminic, antihypertensive, anti-inflammatory, antinociceptive, antioxytocic, antiparasitic, antiviral, diuretic, hematological, hepatoprotective, hypoglycemic, immunopotentiating, wound-healing, and respiratory-stimulant properties.54,56

At least 38 clinical studies have investigated N. sativa seed and seed oil for their efficacy for various conditions, including respiratory, diabetic, hepatic, metabolic, mental, and dyspeptic disorders, male infertility, and others.

One 2017 prospective, phase II, randomized, double-blind, placebo-controlled (RDBPC) study explored the effects of cold-pressed N. sativa oil (NSO; 0.7% thymoquinone; Marnys Cuminmar; Cartagena, Spain) on subjects with asthma. For four weeks, participants (N = 80) took either 500 mg of NSO twice daily or placebo. Compared to placebo, the NSO group showed a significant improvement in mean Asthma Control Test scores, as well as a significant reduction in blood eosinophils, which play a major role in asthma inflammation. There was a trend toward improved pulmonary function and peak expiratory flow in the NSO group that did not reach statistical significance, and there was no significant change in total serum immunoglobulin E (IgE) levels between groups. The authors recommend that “future studies should follow patients for a longer period and use additional outcomes to validate the benefits of NSO in asthma.”57

Another RDBPC study, published in 2008, evaluated the effects of a boiled aqueous extract of nigella seed (NS; 50 mg/mL; no additional information provided) on subjects with respiratory symptoms including chest tightness, breathlessness, cough, and wheezing as a result of chemical inhalation. The participants (N = 40) were an average of 48.2 ± 11.91 years old and the exposure had occurred 18-20 years previously. Each participant drank either the NS extract (0.375 mL/kg of body weight) or a placebo solution daily for two months. Participants received medical exams wherein respiratory symptoms were measured at baseline, 30 days, and the end of the intervention. There were no significant differences between groups at baseline. Significant improvements in all symptoms were seen in the NS group at visits two (day 30) and three (day 60) compared to baseline, except for morning wheeze and cough at day 30. All symptoms were significantly improved by the end of the study compared to day 30 in the NS group. Additionally, all symptoms were significantly reduced in the NS group at day 30 and the end of the study compared to placebo.58

Six additional studies have investigated the effects of nigella on respiratory issues. Three of these studies addressed allergic rhinitis: One study found no significant improvement with 0.6-0.8 mg/kg NSO three times daily over six weeks59; one found significant improvement in symptoms over one month with 2 g NS once daily60; and one claimed improvement in symptoms with NSO but did not specify the dosage.61 Another study on asthma, which tested 1 and 2 g/day of NS, found that both doses resulted in significant improvements in markers at six and 12 weeks compared to baseline.62 One study on lower respiratory tract illness in children reported significant improvement compared to baseline in pulmonary index scores and some improvement in peak expiratory flow rate with daily administration of NSO (0.1 mL/kg of body weight) over 14 days.63 Finally, one study that investigated the effect of a NSO nasal spray (22 mg cold-pressed NSO/25 mL spray) on nasal symptoms in elderly patients for two weeks found that nasal dryness, obstruction, and crusting improved significantly with NSO treatment compared to a saline solution.64

At least two studies have assessed the effects of nigella on patients with rheumatoid arthritis (RA). In one RDBPC study from 2014, patients with RA (N = 42) were randomly assigned to receive either 500 mg NSO (produced by Barij Essence Pharmaceutical Co.; Kashan, Iran; soft gel capsules containing 500 mg of cold-pressed NSO) or placebo (paraffin) twice daily for eight weeks. Blood samples were taken at baseline and the end of the study to measure markers of inflammation (serum tumor necrosis factor alpha [TNF-] and interleukin 10 [IL-10]) and oxidative stress (serum malondialdehyde [MDA] and nitric oxide [NO]). The NSO group experienced a significant increase in serum IL-10, and a significant decrease in serum MDA and NO, compared to placebo. No significant changes in other biomarkers were observed between or within groups. Nevertheless, these results suggest that NSO could be a valuable adjunct therapy in RA, as it improves certain markers of inflammation and oxidative stress in patients.65

Another placebo-controlled study, published in 2012, investigated the effects of nigella in female patients with RA. After taking starch-filled placebo capsules twice daily for one month, subjects (N = 40) took 500 mg of cold-pressed NSO twice daily for an additional month. Investigators reported significant improvements in the patients’ Disease Activity Scores (a clinician-rated measure of joint swelling and tenderness) compared to ratings taken both before and after the one-month placebo period.66

At least two studies have investigated the impact of nigella on mental and cognitive health. In one 2013 RDBPC clinical trial, 40 healthy elderly volunteers were randomly assigned to take 500 mg crushed and encapsulated NS (no additional information provided) or placebo twice daily for nine weeks. Compared to baseline, the test group experienced significant differences in scores on various measures of memory, attention, and cognition, including logical memory tests I and II, a digit span memory assessment (total score), and the Rey-Osterrieth complex figure test (30-minute delayed recall and percent score). There were also significant differences compared to baseline in the time taken to complete a letter cancellation test and trail-making tests A and B. The authors suggested that additional studies should be undertaken with large populations of patients with Alzheimer’s disease over a longer period of time to determine if NS can enhance memory, attention, and cognition in that population.67

Another RDBPC study explored the effectiveness of nigella in treating mood, anxiety, and cognition. Young men (N = 48; 14-17 years old) were randomly assigned to take 500 mg crushed and encapsulated NS (no additional information provided) or placebo daily for four weeks. Compared to baseline, there was a statistically significant improvement in scores on the Bond-Lader visual analog scale (a measure of mood) for the NS group, but no statistically significant difference between the NS group and placebo group. There was also a statistically significant decrease in State-Trait Anxiety Inventory scores in the treatment group over four weeks compared to placebo. Both immediate free recall and delayed recall improved significantly over four weeks in the treatment group only. The authors postulated that cognition may have improved due to the improvements in anxiety and mood, and suggested that further long-term studies are warranted.68

A 2016 RDBPC study examined the effect of nigella on Hashimoto’s thyroiditis, an immunological condition that impacts the thyroid gland. Patients with Hashimoto’s (N = 40) were randomly assigned to take 2 g of ground NS (prepared by Goldaru Pharmaceutical Co.; Isfahan, Iran; no additional information provided) daily or placebo. The NS group experienced significantly reduced body weight, body mass index (BMI), and hip and waist circumference over eight weeks compared to the placebo group. Additionally, serum concentrations of thyroid stimulating hormone (TSH) and anti-thyroid peroxidase (anti-TPO) antibodies decreased in the NS group over eight weeks, while serum triiodothyronine (T3) increased. While there was no change in the concentration of nesfatin-1 (a neuropeptide involved in the regulation of hunger and fat storage) during the study, the authors noted that changes in anthropometric variables (weight, BMI, and hip and waist circumference) and thyroid hormones (TSH, anti-TPO, and T3) are often significant predictors of changes in nesfatin-1 concentrations.69

In a 2014 randomized, double-blind, controlled trial, NSO (verified seeds, dried, ground, and extracted with 96% ethanol, which was later evaporated) was compared to fish oil for the treatment of vitiligo, a condition characterized by a loss of skin pigmentation. Patients with vitiligo (N = 52) were randomly assigned to apply NSO or fish oil on lesions twice daily for six months. By the end of the study, Vitiligo Area Scoring Index (VASI) scores had improved significantly in the NSO group compared to the fish oil group. There were no significant changes in VASI scores between groups in the first three months; not until the fourth month of the study did significant improvement appear in the NSO group.70

A 2016 randomized, triple-blind, placebo-controlled trial investigated the effectiveness of NSO in treating cyclic mastalgia. Female patients diagnosed with cyclic mastalgia (N = 156; 25-45 years old) were randomly assigned to apply twice daily 2 g of NSO gel (a gel base combined with cold-pressed NSO; Barij Essence Pharmaceutical Co.; Kashan, Iran), 20 mg of topical diclofenac, or a placebo gel for two menstrual cycles. There were no significant differences in patient characteristics or baseline pain scores between groups. Pain scores in active treatment groups also did not differ significantly at cycles one and two. However, both active treatment groups experienced a significant decrease in pain scores by the end of the study compared to baseline and placebo. The authors posited that thymoquinone, unsaturated fatty acids, and carvacrol may play a part in NSO’s effectiveness for treating cyclic mastalgia. They also stated that the main shortcoming of the study was the lack of follow-up, which might have been helpful since recurrence of cyclic mastalgia is common.71

Two outcomes from a single RDBPC study were published in 2015 and 2016 on NSO and cardiovascular risk, and NSO and inflammation, respectively. Obese women (N = 84; 25-50 years old) took 3 g per day of cold-pressed NSO (Dana Co.; Tabriz, Iran) or placebo and followed a low-calorie diet for eight weeks. In the cardiovascular-risk arm of the study, the women in the NSO group experienced significant decreases compared to baseline in weight, waist circumference, and levels of triglycerides and very-low-density lipoprotein (VLDL). The authors suggested that NSO supplementation combined with a low-calorie diet may reduce cardiometabolic risk factors in obese women, but they noted that more studies are needed to assess the efficacy of NSO as a complementary therapy.72 In the second arm of the study, NSO significantly decreased serum levels of TNF- and high-sensitivity C-reactive protein compared to placebo. No significant changes were seen in IL-6 levels. Based on these findings, the authors concluded that NSO supplementation and calorie-restriction may modulate systemic inflammatory biomarkers in obese women but that more studies are needed to clarify the findings.73

A 2015 study assessed the effects of the previously mentioned NSO preparation on oxidative stress in obese women (N = 50; 25-50 years old). Investigators reported significant weight loss in the NSO group compared to the placebo group after eight weeks. Additionally, significant changes in superoxide dismutase (SOD, a natural antioxidant enzyme) occurred in the NSO group compared to the placebo group.74

Three studies of varying quality have been conducted on nigella for functional dyspepsia. In one RDBPC study, 70 patients diagnosed with functional dyspepsia took either a traditional formula consisting of 5 mL cold-pressed NSO, mineral oil, and honey (Barij Essence Pharmaceutical Co.; Kashan, Iran) or placebo daily for eight weeks. In both groups, significant decreases in dyspepsia severity scores as measured by the Hong Kong index of dyspepsia severity were seen in the second, fourth, and eighth weeks, but mean scores and the rate of Helicobacter pylori infection for the NSO group were significantly lower than in the placebo group at the end of the study. Additionally, there was a significant difference in quality of life between the NSO and placebo groups at eight weeks.75

A 2015 meta-analysis and systematic review assessed 17 randomized, controlled trials that examined the effects of N. sativa on plasma lipid concentrations. The authors suggested that there was a significant association between NS supplementation and reduction in total cholesterol and triglyceride levels. No significant effects were seen on high-density lipoprotein (HDL) cholesterol levels. NSO performed better than NS powder in lowering total serum cholesterol and low-density lipoprotein (LDL) cholesterol, but only NS powder was found to increase HDL cholesterol. The authors recommended that further randomized, controlled trials are needed to explore nigella’s benefits for cardiovascular health.76

FUTURE OUTLOOK

There are no known comprehensive reports available on the conservation status of wild N. sativa in its native habitat. However, it has been cultivated for thousands of years, and the commercial supply is not known to originate from wild populations. Historically, the main producers and exporters of cultivated N. sativa seed have been Egypt, Turkey, Syria,18 and India.12 Because N. sativa seed is widely used in the Indian systems of medicine, the plant is cultivated on a large scale and estimated to be traded in annual quantities in excess of 100 metric tons (MT).20 Certified organic N. sativa seed comes predominantly from farms in Egypt and, to a lesser extent, Turkey.10

Market prices for cultivated N. sativa seed from the two main countries of origin, Egypt and India, have generally been stable. In late 2016, prices for full container load (FCL) quantities of conventional N. sativa seed from India ranged from $2,258 to $2,750 per MT (Free on Board [FOB]* Mumbai Port). Conventional Egyptian material sold for $2,900 per MT (FOB Alexandria Port). Some Egyptian exporters were also offering FCL quantities of fair trade and certified organic N. sativa seed for $3,000 per MT (FOB Alexandria Port).77

The quantities of seed needed for use in the various traditional African and Asian systems of medicine, as well as for culinary use, are already considerable, and due to the significant levels of promising new clinical research, it seems likely that production and demand will increase, especially for value-added forms, such as oils and extracts. 

—Gayle Engels and Josef Brinckmann
 

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