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Nigella sativa L. Scientific name: Nigella sativa L. Synonym: Nigella cretica Mill. Family: Ranunculaceae Genus: Nigella Species: sativa Common Name: Kalonji, fennel flower, nutmeg flower, black caraway, Roman coriander. Parts Used: Dried fruits, Seeds. Plant Description: Nigella sativa grows to 20–30 cm (7.9–11.8 in) tall, with finely divided, linear (but not thread-like) leaves. The flowers are delicate, and usually coloured pale blue and white, with five to ten petals. N. sativa fruit is a large and inflated capsule composed of three to seven united follicles, each containing numerous seeds. Chemical Constituents: N. sativa seeds contain fixed oils (36% to 38%), proteins, alkaloids, saponin (melanin), and essential oil (0.4% to 2.5%). The fixed oil is composed mainly of unsaturated fatty acids (linoleic and oleic acids). The major component of the essential oil is thymoquinone (28% to 57%). Four alkaloids have been isolated: nigellicine and nigellidine (indazoles), and nigellimine and nigellimine N-oxide (isoquinolines).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. Thymoquinone, dithymoquinone (nigellone), thymohydroquinone, and thymol are considered the main active constituents.

Isolated active chemical constituents of Nigella sativa L.

Thymoquinone Dihydrothymoquinone Thymol

Thymohydroquinone Nigellicine Nigellidine

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Nigellimine Palmitic acid

Arginine Methionine Lysine

Action of Herb: Analgesic (Pain-Killing), anti-bacterial, anti-inflammatory, anti-ulcer, anti-cholinergic, anti-fungal, anti-hypertensive, anti-oxidant, anti-spasmodic, anti-viral, bronchodilator, gluconeogenesis inhibitor (anti-diabetic), hepato-protective (liver protecting), hypotensive, insulin sensitizing, interferon inducer, leukotriene antagonist, renoprotective (kidney protecting), tumor necrosis factor alpha inhibitor, anthelmintic, carminative, diaphoretic, digestive, diuretic, emmenagogue, galactogogue, parasiticide, stimulant. Medicinal Uses: Kalanji has been used for a number of illnesses and conditions including GI disorders, hypertension, diabetes, inflammation, cough, bronchitis, headache, eczema, fever, dizziness, and influenza. Studies have been conducted on its immunoprotective and anticancer effects; anti-inflammatory, analgesic, and antioxidant actions; and anti-diabetic, anti-hypertensive, anti-microbial, and anti-parasitic properties. More human studies are needed before kalanji can be recommended for any indication. Dosage:1-2 grams, 3 grams, for hot temperament-2gms, for cold temperament-7 grams.

Adults (18 years and older) For acne, inhalation of vapor of hot water with 1/2 teaspoon of N. sativa oil has been used. For addiction (opiates), 500 milligrams of dried black seeds has been taken by mouth three times daily for up to 12 days. For allergies, 40-80 milligrams per kilogram of black seed oil has been taken by mouth three times daily for up to eight weeks. As an antifungal, the affected area of skin is wiped with cider vinegar, followed by application of N. sativa oil. The process is repeated if necessary. For anxiety, 1/2 teaspoon of N. sativa oil has been taken by mouth with herbal tea. For arthritis, one teaspoon of N. sativa oil with one teaspoon of olive oil has been taken by mouth three times daily. For atopic dermatitis, an ointment containing 15% black seed oil has been applied to the skin for four weeks. For bruises, one teaspoon of N. sativa oil with one teaspoon of olive oil has been taken by mouth three times daily.

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For cold symptoms, one teaspoon of N. sativa oil has been taken by mouth three times daily. For colic, N. sativa oil has been warmed and used to massage the abdomen. For cough, the back and chest have been rubbed with N. sativa oil. For diabetes, 2.5 milliliters of N. sativa oil has been taken by mouth twice daily for six weeks, in addition to existing metformin. For diarrhea, one teaspoon of N. sativa oil with a cup of yogurt has been taken by mouth twice daily. For earache, 1/2 teaspoon of N. sativa oil mixed with 1/2 teaspoon of olive oil has been warmed and dripped into the ear, followed by placement of a hat or scarf over the ear. For headache, 1/2 teaspoon of N. sativa oil has been taken by mouth after a meal three times daily. For hair loss, 1/2-1 teaspoon of N. sativa oil has been applied to the scalp after the scalp has been stroked thoroughly with lemon, left for 15 minutes, then washed and dried. For headache, the forehead and sides of the head and part of the face near the ears have been rubbed with N. sativa oil. For high blood lipids, 2.5 milliliters of N. sativa oil has been taken by mouth twice daily for six weeks, in addition to existing lipid-lowering agents. For high blood pressure, 100 and 200 milligrams of boiled extract has been taken by mouth twice daily for eight weeks. Based on traditional use, one teaspoon of N. sativa oil has been taken by mouth in any hot drink with two cloves of garlic before breakfast. For influenza, one teaspoon of N. sativa oil has been taken by mouth three times daily. For muscle soreness, one teaspoon of N. sativa oil with one teaspoon of olive oil has been taken by mouth three times daily. For respiratory disorders N. sativa boiled water extract (0.375 milliliters of a 50 milligrams per milliliter solution per kilogram) has been taken by mouth for two months. For asthma, 15 milliliters of a 0.1% boiled extract per kilogram has been taken by mouth daily for three months. For asthma, 50 or 100 milligrams of boiled N. sativa extract per kilogram has been taken by mouth. For asthma, the back and chest have been rubbed with N. sativa oil. For asthma and cough, inhalation of vapor of boiling water with one teaspoon of N. sativa oil has been used. For rheumatic diseases, one teaspoon of N. sativa oil with one teaspoon of olive oil has been taken by mouth three times daily. For sinusitis, one teaspoon of N. sativa oil has been taken by mouth daily in chronic sinusitis cases; in acute sinusitis cases, one teaspoon of N. sativa oil has been taken by mouth three times daily. Inhalation of N. sativa oil through the nose via a vapor bath has been used. For stomach disorders, mint tea with lemon taken by mouth with one teaspoon of N. sativa oil three times daily or until symptoms are relieved. Children (under 18 years old) For allergies, 40-80 milligrams of black seed oil per kilogram has been used three times daily for up to eight weeks. For epilepsy, an aqueous extract of N. sativa seed (40 milligrams per kilogram per hour) has been used together with standard treatment for four weeks. Side Effects: allergic dermatitis Contraindications: diabetes, low blood pressure, surgery, Drug Interactions: N. sativa may interfere with the action of certain types of cancer therapies, such as radiation therapy or chemotherapy, which destroy cells that grow rapidly. Additionally, concomitant use of N. sativa and anti-hypertensive drugs may cause a sudden drop in your blood

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pressure levels. Ginkgo biloba, garlic and saw palmetto concomitant use with N. sativa may increase risk of bleeding, agents processed by the kidneys. N. sativa may also interact with analgesics, anthelmintics, antianxiety agents, anti-arthritic agents, anti-asthma drugs, antibiotics, anti-cholinergics, anti-convulsant agents, anti-fungals, anti-histamines, anti-lipemic agents, antineoplastic agents, antiobesity agents, antiprotozoals, antipyretics, antiretroviral agents, anti-ulcer agents, anti-virals, brucellosis vaccine, cardiovascular agents, cisplatin, COX-2 inhibitors, cyclosporin A, diuretics, doxorubicin, fertility agents, gastrointestinal agents, gentamicin, hepatotoxic agents, hormonal agents, ibuprofen, ifosfamide, immunosuppressants, leukotriene receptor antagonists, levodopa, neurologic agents, nicotinamide, nonsteroidal anti-inflammatory agents (NSAIDs), oxytetracycline, oxytocics, pentylenetetrazol, permeation enhancers, radioprotective drugs, renally eliminated agents, reserpine, respiratory agents, rotenone, smooth muscle relaxants, warfarin. Microscopic study of N. sativa Margout et al. (2013) carried out microscopic study of N. sativa seeds and observed: brick red external tegument consisting of polygonal cells that were very slightly embossed; grey-colored albumen consisting of thin-walled cells; several oil droplets; tissue surrounding the albumen was orange-brown consisting of a single layer of polygonal cells that were almost aligned.

Figure: Cross-sections of the external teguments of N. sativa

MargoutD, Kelly MT, MeunierS, AuingerD, Yves PelissierY,LarroqueM. 2013. Morphological, microscopic and chemical comparison between Nigella sativa L. cv(black cumin) and Nigella damascena L. cv. Journal of Food,

Agriculture & Environment; 11(1):165-171. Phytochemical analysis of N. sativa Phytochemical analysis of N. sativa seeds extract was carried out by Ishtiaq et al. (2013). See the table below.

Table: Phytochemical analysis of N. sativa seed extracts

+ = weakly present, ++ = moderately present, +++= strongly Present, - = Not present

Int. J. Agric. Biol., Vol. 15, No. 6, 2013 Ishtiaq S, Ashraf M, Hayat MQ, Asrar M. 2013. Phytochemical analysis of Nigella sativa and its anti-bacterial

activity against clinical isolates identified by ribotyping. Int J AgricBiol; 15: 1511–1156.

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Thin layer chromatography of N. sativa Suthar et al. (2010) carried out thin-layer chromatography of methanolic, ethanolic and aqueous extracts of N. sativa using Diethylether: Benzene (1:1) solvent system. See the figures below.

A B C Figure: A) Chromatographic finger printing of the plant extracts. B) Chromatographic analysis at UV 254 nm. C) Chromatographic analysis at UV 366 nm. Chromatographic finger printing of plant extracts. 1. Thymoquinone standard. (fraction-1), 2.Methanolic extract.(fraction-2), 3.Ethanolicextract. (fraction-3). 4. Water extract. (fraction-4) Suthar MP, Patel PN, Shah TG, Patel RK. 2010. In vitro Screening of Nigella sativa Seeds for Antifungal Activity.

International Journal of Pharmaceutical and Applied Sciences; 1(2): 84-91. UV-Visible spectroscopy of N. sativa Velho-Pereira et al. (2012) carried out UV-Visible spectroscopy of N. sativa extract.

Figure: UV-Visible Spectroscopy of N. sativa extract

Velho-Pereira R, Kumar A, Pandey BN, Mishra KP, Jagtap AG. 2012. Radioprotection by macerated extract of Nigella sativa in normal tissues of fibrosarcoma bearing mice. Indian Journal of Pharmaceutical Sciences; 74(5):

403-414.

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FT-IR spectroscopy of N. sativa Mahesar et al. (2014) carried out FT-IR spectroscopy of N. sativa commercial and fresh extracted oils. See the figure below.

Figure: FTIR spectra of commercial N. sativa oil (A) and freshly extracted oil from N. sativa seed (B).

Mahesar SA,Kandhro AA,Khaskheli AR, Talpur MY, Sherazi STH. 2014. SB-ATR FTIR Spectroscopic Monitoring of Free Fatty Acids in Commercially Available Nigella sativa (Kalonji) Oil. Journal of Spectroscopy: 1-5.

GC-MS analysis of N. sativa Velho-Pereira et al. (2012) carried out GC-MS analysis of N. sativa extract.

Figure: GC-MS of N. sativa extract

Velho-Pereira R, Kumar A, Pandey BN, Mishra KP, Jagtap AG. 2012. Radioprotection by macerated extract of Nigella sativa in normal tissues of fibrosarcoma bearing mice. Indian Journal of Pharmaceutical Sciences; 74(5):

403-414.

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Anti-microbial activity of N. sativa Gerige et al. (2009) reported antimicrobial activity against 19 microbes by disc diffusion method.

Table: Antimicrobial activity of the N. sativa volatile oil by Disc diffusion method.

Nt=not tested, Clindamycin 2mg/ml for S. aureus, Gentamicin 2mg/ml for Ps. aeruginosa, Proteus vulgaris; Tetracycline3mg/ml E. coli and B. subtilus Clotrimazole 5mg/ml for C. albicans; Nystain 10mg/ml for A. nigerand T. mentagrophytes. MFBF: number of strains from the collection of microorganisms of the Dept. of Microbiology and biotechnology, Anantapur. MTCC: Microbial type culture collection centre. Gerige SJ, Gerige MKY, RaoM, Ramanjaneyulu. 2009. GC-MS Analysis of Nigella sativa Seeds and Antimicrobial

Activity of its Volatile oil.Braz. Arch. Biol.Technol; 52(5): 1189-1192. Anti-hypertensive effect of N. sativa Najmi et al. (2013) carried out an open labeled study to test the efficacy of N. sativa as an anti-hypertensive in patients of metabolic syndrome. The results of the study revealed that N. sativa can be used as add on drug therapy in patients of metabolic syndrome with elevated blood pressure. Table: Variables of Blood Pressure and Lipid Metabolism At baseline and after the intervention period in

both groups

Data are mean ± SD; †significantly different from baseline (P < 0·001)

Najmi A, Nasiruddin M, Khan RA, Haque SF. 2013. Indigenous herbal product Nigella sativa proved effective as an anti-hypertensive in metabolic syndrome. Asian J Pharm Clin Res; 6(1): 61-64.

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Table: Post treatment Mean ± SD of standard and N. sativa group

Data are mean ± SD; ‡ significantly different from the standard group (P value < 0.001)

Najmi A, Nasiruddin M, Khan RA, Haque SF. 2013. Indigenous herbal product Nigella sativa proved effective as an anti-hypertensive in metabolic syndrome. Asian J Pharm Clin Res; 6(1): 61-64.

Immunomodulatory effect of N. sativa Boskabady et al. (2011) evaluated the effect of N. sativa extract on lung pathology and blood interleukin-4 (IL-4) and interferon-γ (IFN-γ) of sensitized guinea pigs. The revealed the preventive effect of N. sativa extract on lung inflammation of sensitized guinea pigs. The preventive effects of long-term administration of hydro-ethanolic extract of N. sativa (during sensitization period, i.e., (32±1) d) on pathological changes of the lung and the level of cytokines (IL-4 and IFN-γ) were examined. The results showed increased IL-4 and IFN-γ in sensitized guinea pigs. Histological evaluations of the lung tissues also showed the infiltration of eosinophils and lymphocytes in the lung parenchyma, epithelial damage, mucosal plug, oedema, basement membranethickening, and muscular hypertrophy in sensitizedguinea pigs.

Figure: Photographs of a lung specimen in the control (a), sensitized (b), and low (c) and high (d) doses of N. sativa extract treated sensitized guinea pigs. The photograph of the sensitized group showed local epithelial necrosis (N), mucosal plug (P), severe eosinophil infiltration (EI), and lymphocyte infiltration (LI), but these changes were improved in the treated animals with both doses of the extract. Magnification: (a, b, c) 10×40; (d) 10×60

Boskabady MH, Keyhanmanesh R, Khameneh S, Doostdar Y, Khakzad MR. 2011. Potential immunomodulation effect of the extract of Nigella sativa on ovalbumin sensitized guinea pigs. J Zhejiang Univ-Sci B (Biomed &

Biotechnol); 12(3):201-209.

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Analgesic effect of N. sativa Bashir and Qureshi (2010) carried out the analgesic activity to study the effect of ethanolic extract of N. sativa seeds on experimentally-induced pain in albino mice. The results of the study exhibited that ethanolic extract of N. sativa possessed significant analgesic effect.

Table: Effect of ethanolic extract of N. sativa and Diclofenac sodium on writhing in mice.

*p < 0.001 as compared to control.

Bashir MU, Qureshi HJ. 2010. Analgesic effect of Nigella sativa seeds extract on experimentally induced pain in albino mice. Journal of the College of Physicians and Surgeons Pakistan; 20 (7): 464-467.

Neuro-pharmacological studies on N. sativa Bano et al. (2014) evaluated the behavioral effect of aqueous extract of N. sativa seeds in rats using open field activity, home cage, elevated plus maze and light dark behavioral modules. The oral administration of aqueous extract of N. sativa for six weeks increased locomotive activity in rats in the tested behavioral models. Galactagogue action ofN. sativa Al-Snafi et al. (2014) evaluated the galactagogue effect of N. sativa seeds on lactating mice and observed that N. sativa significantly increased serum prolactin level and the weight of the Litter as compared to the controlgroup.

Table: Serum prolactin level in females given control diet in comparison of female kept on N. sativa containing diet.

Al-Snafi AE, Majid WJ, Talab TA. 2014. Galactagogue action of Nigella sativa seeds. IOSR Journal of Pharmacy;

4(6): 58-61. Table: The increase in the weight of the litter of the female mice kept on N. sativa containing diet

compared with control.

*Mean of the means of litter weight of all mothers in the group

Al-Snafi AE, Majid WJ, Talab TA. 2014. Galactagogue action of Nigella sativa seeds. IOSR Journal of Pharmacy; 4(6): 58-61.

Effectiveness of N. sativa in eradication of H. pylori infection in non-ulcer dyspeptic patients: Salem et al. (2015) evaluated the efficacy of N. sativa in eradication of H. pylori infection in non-ulcer dyspeptic patients. The results of the study revealed that N. sativa seeds possess

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clinically useful anti H. pylori activity, comparable to triple therapy (Clarithromycin +Amoxicillin + Omeprazole). A preliminary study on the prophylactic effect of N. sativa against Cyclophosphamide in the ovarian follicles of matured adult mice Kamarzaman et al. (2014) carried out study to assess the follicle preservation in mature female mice with the provision of N. sativa oil against effects of cyclophosphamide which can cause ovarian follicular loss.The results of the study exhibited prophylactic activity of N. sativa in the reproductive system of female mice. See the tables below.

Table: Mean ± SD total distribution of normal and degenerated follicles after cyclophosphamide and N. sativa oil exposures at 5 days.

a = No significant different between groups. b = Significantly different between groups, p<0.05. c = Significantly different between groups, p<0.001. Kamarzaman S, Shaban M, Rahman SA. 2014. The prophylactic effect of Nigella sativa against cyclophosphamide in the ovarian follicles of matured adult mice: A preliminary study. The Journal of Animal & Plant Sciences; 24(1):

81-88. Table: Mean ± SD diameters of the ovaries in the control, cyclophosphamide alone and

cyclophosphamide co-treated with N. sativa oil groups.

*Significantly different from control groups, p<0.05. † Significantly different from cyclophosphamide 5-days group, p<0.05. Kamarzaman S, Shaban M, Rahman SA. 2014. The prophylactic effect of Nigella sativa against cyclophosphamide

in the ovarian follicles of matured adult mice: A preliminary study. J Animal & Plant Sciences; 24(1): 81-88. Hypolipidemic effects of N. sativa in menopausal women Ibrahim et al. (2014) carried out randomized control trial to evaluate hypolipidemic effects of N. sativa in menopausal women. The results of the study showed that N. sativa caused significant decrease in TC, LDL and TG, and slight increase in HDL among menopausal women receiving N. sativa powder at a dose of 1 g daily for two months compared to placebo group. Preventive effect of N. sativa against Amphotericin B induced nephrotoxicity Majeed and Tahir (2014) evaluated the Amphotericin B induced nephrotoxicity and its prevention by administration of N. sativa extract in albino mice. The results of the study revealed that N. sativa when co-administered with Amphotericin B significantly contained serum urea and serum creatinine level simplying thereby that Amphotericin B induced nephrotoxicity was significantly reduced. However, when N. sativa extract was given after Amphotericin B, the

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toxic effects of the drug persisted unabated thus indicating that N. sativa protects but do not ameliorate the toxic effects of the drug. Hepato-protective effect of N. sativa Jaswal and Shukla (2015) evaluated the effect of aqueous extract of N. sativa on CCl4 induced liver toxicity in rats. The results of the study confirmed the presence of hepato-protective activity in N. sativa aqueous extract. Anti-osteoporotic effects of N. sativa Atlan et al. (2007) carried out anti-osteoporotic study on steptozocin-induced diabetic rats and the results of the study revealed that the N. sativa was more effective in reversing the osteoporotic changes and improving the bone strength of steptozocin-induced diabetic rats, when used with parathyroid hormone, than either treatment alone. Effects of N. sativa on lipid profile in patients with stable coronary artery disease Tasawar et al. (2011) assessed the effects of N. saitva on the lipid profile in eighty cardiac patients that visited Ch. Pervaiz Elahi Institute of Cardiology, Multan. The eighty subjects were divided into two groups (interventional and non-interventional) through random stratification (n = 40/group) by weight. The interventional group was given N. sativa and statin while non-interventional group was given only statin daily. The results of the study revealed that N. sativa significantly changed lipid profile in a therapeutically beneficial way in stable coronary artery patients that underwent treatment in the study. Gastro-protective effect of N. sativa Al Mofleh et al. (2008) determined the effect of an aqueous suspension of N. sativa seeds against various necrotizing agents and indomethacin-induced gastric ulcer in rats. The results of the study displayed that oral administration of an aqueous suspension of N. sativa prevents gastric mucosal injuries caused by ethanol and strong alkalies and also inhibited gastric acid secretions. Anti-cancer activity of N. sativa Salomi et al. (1992) carried out anti-tumour activity of N. sativa seed extract and found that the crude methanolic extract of theN. sativa seeds exhibited a strong cytotoxic action on Elrichascites carinoma, Dalton’s ascites lymphoma and sarcoma 180 whereas exerting minimal cyto-toxicity to the normal lymphocytes. In another study carried out by Farah and Begum(2003), the aqueous and alcoholic extract of N. sativa alone or in combination with H2O2 as an oxidative stress or were found to be effective in in vitro inactivating MCF-7 breast cancer cells. Anti-malarial activity of N. sativa Various extracts of N. sativa found to show anti-plasmodial activity against both in vivo and in vitro plasmodia infections. It shows 100% inhibition of the parasite growth (Plasmodium falciparum) at concentration 50 µg/ml. N. sativa showed dose-dependent activity against parasite in the research works carried out by Abdulelah et al.(2007) and El-Hadi et al. (2010). References Abdulelah HAA, Zainal-Abidin BAH. 2007. In vivo anti-malarial tests of Nigella sativa (Black Seed) different

extracts. Am. J. Pharmacol. Toxicol; 2: 46-50. Al Mofleh IA, Alhaider AA, Mossa JS, Al-Sohaibani MO, Al-Yahya MA, Rafatullah S, Shaik SA. 2008. Gastro-

protective Effect of an Aqueous Suspension of Black Cumin Nigella sativa on Necrotizing Agents-Induced Gastric Injury in Experimental Animals. Saudi J Gastroenterol; 14(3): 128–134.

Al-Snafi AE, Majid WJ, Talab TA. 2014. Galactagogue action of Nigella sativa seeds. IOSR Journal of Pharmacy; 4(6): 58-61.

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Altan MF, Kanter M, Donmez S, Kartal ME, Buyukbas S. 2007.Combination therapy of Nigella sativa and human parathyroid hormone on bone mass, biomechanical behavior and structure in streptozotocin-induced diabetic rats.ActaHistochem; 109(4): 304-14.

Bano F, Ahmed A, Parveen T,Haider S. 2014. Anxiolytic and hyperlocomotive effects of aqueous extract of Nigella sativa L. seeds in rats. Pak J PharmSci; 27(5): 1547-1552.

Bashir MU, Qureshi HJ. 2010. Analgesic effect of Nigella sativa seeds extract on experimentally induced pain in albino mice. Journal of the College of Physicians and Surgeons Pakistan; 20 (7): 464-467.

Boskabady MH, Keyhanmanesh R, Khameneh S, Doostdar Y, Khakzad MR. 2011. Potential immunomodulation effect of the extract of Nigella sativa on ovalbumin sensitized guinea pigs. J Zhejiang Univ-Sci B (Biomed &Biotechnol); 12(3): 201-209.

El-Hadi MA, Bakri YM, Yousif G. 2010. Mohammed and Hassan S. Khalid. Antiplasmodial Activity of Some Medicinal Plants Used in Sudanese Folk-medicine. Environ. Health Insights; 4: 1-6.

Farag MA, El Sayed AM, El Banna A, Ruehmann S. 2015. Metabolomics reveals distinct methylation reaction in MeJA elicited Nigella sativa callus via UPLC–MS and chemometrics. Plant Cell, Tissue and Organ Culture (PCTOC); 122: 453-463.

Farah IO, Begum RA. 2003. Effect of Nigella sativa and oxidative stress on the survival pattern of MCF-7 breast cancer cells. Biomed SciInstrum; 39: 359-364.

Gerige SJ, Gerige MKY, Rao M, Ramanjaneyulu. 2009. GC-MS Analysis of Nigella sativa Seeds and Antimicrobial Activity of its Volatile oil.Braz. Arch. Biol.Technol; 52(5): 1189-1192.

Gholamnezhad Z, Rafatpanah H, Sadeghnia HR, Boskabady MH. 2015. Immunomodulatory and cytotoxic effects of Nigella sativa and thymoquinone on rat splenocytes. Food and Chemical Toxicology; 86, 72-80.

Ibrahim RM, Hamdan NS, Mahmud R, Imam MU, Saini SM, Rashid SNA, Ghafar SAA, Latiff LA, Ismail M. 2014. A randomised controlled trial on hypolipidemic effects of Nigella sativa seeds powder in menopausal women. Journal of Translational Medicine; 12: 82.

Ishtiaq S, Ashraf M, Hayat MQ, Asrar M. 2013. Phytochemical analysis of Nigella sativa and its anti-bacterial activity against clinical isolates identified by ribotyping.Int J AgricBiol; 15: 1511–1156.

Jaswal A, Shukla S. 2015. Therapeutic efficacy of Nigella sativa Linn.seed extract against CCl4 induced hepatic injury in wistar rats. Indian Journal of Experimental Biology; 53: 44-50.

Kamarzaman S, Shaban M, Rahman SA. 2014. The prophylactic effect of Nigella sativa against cyclophosphamide in the ovarian follicles of matured adult mice: A preliminary study. The Journal of Animal & Plant Sciences; 24(1): 81-88.

Mahdavi R, Heshmati J, Namazi N. 2015. Effects of black seeds (Nigella sativa) on male infertility: A systematic review. Journal of Herbal Medicine; 5, 133-139.

Mahesar SA, Kandhro AA, Khaskheli AR, Talpur MY, Sherazi STH. 2014. SB-ATR FTIR Spectroscopic Monitoring of Free Fatty Acids in Commercially Available Nigella sativa (Kalonji) Oil. Journal of Spectroscopy: 1-5.

Majdalawieh AF, Fayyad MW. 2015.Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: A comprehensive review. International Immunopharmacology; 28, 295-304.

Majeed N, Tahir M. 2014. Effect of Nigella sativa extract on renal functions in Amphotericin B induced nephrotoxicity in mice. Biomedica; 30(1): 1-4.

Margout D, Kelly MT, Meunier S, Auinger D, Yves Pelissier Y, Larroque M. 2013. Morphological, microscopic and chemical comparison between Nigella sativa L. cv (black cumin) and Nigella damascena L. cv. Journal of Food, Agriculture & Environment; 11(1):165-171.

Salem EM, Yar T, Bamosa AO, Al-Quorain A, Yasawy MI, Alsulaiman RM, Randhawa MA. 2010. Comparative Study of Nigella sativa and Triple Therapy in Eradication of Helicobacter pylori in Patients with Non-Ulcer Dyspepsia. The Saudi Journal of Gastroenterology; 16(3): 207-14.

Salomi NJ, Nair SC, Jayawardhanan KK, Varghese CD, Panikkar KR. 1992. Antitumour principles from Nigella sativa seeds. Cancer Lett; 63(1): 41-46.

Suthar MP, Patel PN, Shah TG, Patel RK. 2010. In vitro Screening of Nigella sativa Seeds for Antifungal Activity. International Journal of Pharmaceutical and Applied Sciences; 1(2): 84-91.

Tasawar Z, Siraj Z, Ahmad N, Lashari MH. 2011. The Effects of Nigella sativa (Kalonji) on Lipid Profile in Patients with Stable Coronary Artery Disease in Multan, Pakistan. Pakistan Journal of Nutrition; 10 (2): 162-167.

Velho-Pereira R, Kumar A, Pandey BN, Mishra KP, Jagtap AG. 2012. Radioprotection by macerated extract of Nigella sativa in normal tissues of fibrosarcoma bearing mice. Indian Journal of Pharmaceutical Sciences; 74(5): 403-414.