Medicinal plants have been used for treating diseases for several decades in various indigenous and traditional systems of medicine. Among the various potential medicinal plants, N. sativa is a dicotyledonous miraculous herb of rananculaceae with a strong historical and religious background (Ahmad et al., 2013). The seeds of N. sativa are the sources of the active ingredient which have been utilized for thousand years as a spice and food preservative, as well as a defending and therapeutic remedy for several disorders (Sultana et al., 2015). Historical use of N. sativa has been mentioned in various religious and ethnic books (Tembhure et al., 2014). In Islam, it is considered as one of the greatest form of healing medicine existed as a remedy for all diseases except death in one of the saying of Prophet Muhammad It is also commended for use on consistent basis in Tibb-e-Nabwi (Prophetic Medicine) (Ahmad et al.,2013; Tembhure et al., 2014; Paarakh, 2010). N. sativa seeds are identified as the curative black cumin in the holy bible; it is also described as the melanthion (little black seed) by Hippocrates and Dioscordes. In the Greco Arab/ Unani-Tibb system of medicine which construct from the work Hippocrates and others Unani physician, his contemporary Galen and Ibn- Sina has regarded N. sativa as a valuable remedy in hepatic and digestive disorder. The famous book of medicine by Ibn-Sina “The cannon of medicine (980-1037) revealed historical importance of N. sativa as seeds that stimulates the body’s energy and help recovery from fatigue and dispiritedness” (Tembhure et al., 2014; Paarakh, 2010). In ayurvedic medicine, the seeds are employed for action like astringent, bitter, stimulant, diuretic, emmenagogue, anti-helminthic and used in jaundice, intermittent fever, dyspepsia, paralysis, piles and skin diseases etc (Paarakh, 2010). The aim of current review is to emphasize the traditional uses, pharmacological investigations that has been carried out on the plant so that the therapeutic potential of the said herb can be further explored for the betterment of humanity. Further study should be performed to investigate its aptitude.

Taxonomic classification

Synonym of N. sativa in various languages(Tembhure et al., 2014; Dymock et al., 2005; Anonymous, 1992; Satyavati et al., 1987)

English: Black cumin, Love-in-a-mist, Fennel flower, Nutmeg flower, Damascena, Devil in the Bush; Arabic: Habatut Barakah; Shuneez; Habbat-us-sauda; Kamune-asvad; Persian: Siyadanah; Hindi: Kalonji, Kalajira; Sankrit: Krishana – Jiraka, Upakunchika,Kaalaajaajee, Sushavee,Ajaji, Kalvanjika, Kalika; Bengali: Mungrela; Malyalam: Karun shiragani; Tamil: Karun shiragam; Talugu: Nillajila; Kannar: Karijirigi

Habitat

N. sativa is a small elegant herb, mostly attained and cultivated in India, Southern Europe, Pakistan, Syria, Turkey, Saudi Arabia and is a native of Southern Europe, North Africa and South West Asia. In India, it is found in Punjab, Himachal Pradesh, Gangetic plains, Bihar, Bengal, Assam, Maharashtra (Sultana et al., 2015; Paarakh, 2010).

Macroscopic feature of plant

It is an annual flowering plant ascending upto 30-60cm with linear-lanceolated leaves and has tap root; the flowers are white, yellow, pink or pale purple color, 5-10 petals on solitary long peduncle; sepals are ovate, acute and clawed. A fruit capsule comprise of 3-7 united follicles, each enclosing black seeds of size 0.2cm x 0.1cm are dicotyledonous, flattened, oblong, tubercular having rough testa containing white oily kernel; slightly aromatic in odor, taste bitter and takes about 10-15 days to germinate. Flowering and fruiting occur from January to April and is cultivated in dry soil in month of November till April (Forounzafar et al., 2014; Phulwaria et al., 2014; Ahmad et al., 2013; Paarakh, 2010; Dymock et al., 2005; Anonymous., 1992; Kirtikar et al., 1987).

Microscopic feature of seed

Transverse section of seed demonstrate single layer of epidermis comprising of elliptical, thick-walled cells covered externally by papillose cuticle. 2-3 layers of parenchymatous cells, a reddish-brown pigmented layer composed of tangentially elongated cells, followed by rectangular, radially elongated cells. Endosperm consists of moderately thick-walled polygonal cells, numerous oil filled globules and embryo entrenched in it (Paarakh, 2010; Ahmad et al., 2013; Anonymous, YNM).

Properties

Temperament (Mizaj): Hot², Dry² (Khan, 2014; Ghani, YNM; Kabiruddin, YNM; Anonymous, 1992) Hot³, Dry³ (Ghani, YNM; Hakeem, YNM).

Taste (Maza): Slightly bitter (Khan, 2014; Kabiruddin, YNM; Anonymous, 1992; Hakeem, YNM), Acrid in taste (Ghani, YNM)

Odour (Boo): Pleasant odour like a lemon (Dymock et al., 2005), strong smell (Hakeem, YNM; Khan, 2014).

Adverse Effect (Muzir): It affect liver (Khan, 2014; Ghani, YNM), cause diphteria (Kabiruddin, YNM; Hakeem, YNM), harms kidney (Hakeem, YNM; Ghani, YNM), lungs and patient with headache (Ghani, YNM).

Main Function (Nafa-e-Khas): Diuretic and Emmenagogue (Mudir-e-Baul wa Haiz) and Jaundice (Yarqaan) (Kabiruddin, YNM; Hakeem, YNM), Abortificient (Mukhrij-e-Janeen), Haemerrhoids (Bawaseer) (Hakeem, YNM).

Corrective (Musleh): Cucumis sativus (Tukhme Khyaar) (Khan.,2014; Ghani, YNM), Sterculia urens (Kateera) (Ghani, YNM; Kabirruddin, YNM; Anonymous, 1992; Hakeem, YNM), Drugs of cold temperament (Sard Ashiyaa) (Kabirruddin, YNM; Hakeem, YNM), Bumbusa arundinacea (Banslochan) (Ghani, YNM; Anonymous, 1992), Vinegar (Sirka) (Ghani, YNM; Anonymous, 1992; Hakeem, YNM), Cichorium intybus (Kasni) (Ghani, YNM)

Substitute (Badl): Olea europeae (Samaghe zaitoon) (Khan, 2014; Ghani, YNM), Lepidium sativum (Tukhme Rashaad) (Khan, 2014; Ghani, YNM), Pimpinella anisum (Anisoon) (Kabirruddin, YNM; Khan, 2014; Ghani, YNM; Hakeem, YNM), Anethum sowa (Sowa Seed) (Khan, 2014; Hakeem, YNM), Hyoscyamus niger (Ajwain Khurasani Seed) (Ghani, YNM; Anonymous, 1992; Khan, 2014)

Important Unani formulations: Habb-e-Hilteet, Jawarish Shoneez, Majoon Kalkalanaj (Kabiruddin, YNM; Anonymous, 1992; Anonymous, YNM); Majoon Fanjnosh, Majoon Kundur (Anonymous, YNM)

Special Use of N. sativa by Ancient Unani Physician:

Externally:

⬥ Jaundice (Yarqaan) - Use as nasal drop (qutoor) by mixing kalonji with mother milk (Kabiruddin, YNM; Ghani, YNM; Khan, 2014; Kirtikar et al., 1987; Anonymous, YNM)

Ayurvedic description (Satyavati et al., 1987)

⬥ Properties

Taste (Rasa): Bitter (Kattu), Pungent (Tikta); Properties (Guna): Lightness (Laghu), Dryness (Rooksha), Sharp (Teekshna); Potency (Veerya): Hot (Ushna).

⬥ Action/ use-

Appetizer (Rochana), Carminative (Deepana), Digestive (Paachana), Pacifier (Vaatakaphahara), Eliminate foul smell (Daurgandhya-naashana), Brass (Pittala), Nootropic drug (Medhya), Purify uterus (Garbhaashayashodhaka), Beneficial for eye (Chakshushya), Phantom tumour (Gulmahara), Decrease emesis (Chardihara), Helps in diarrhoea (Atisaarahara) (vitiated condition of vata and kapha).

Afaal (Pharmacological Action) and Mawaqae istimal (Indications)

Extensive phytochemical studies has been done to isolate and identify the chemical composition of N. sativa. Seeds include 36 to 28% fixed oil, proteins, alkaloid, saponin and 0.4 to 2.5% essential oil (Forouzanfar et al., 2014; Tembhurne et al., 2014). Pharmacological properties of black cumin is mainly due to presence of Thymoquinone (TQ). Important active volatile constituents of N. sativa are thymoquinone (30%-48%), thymohydroquinone, dithymoquinone, nigellone that is the only component of the carbonyl fraction of the oil (Ahmad et al., 2013), α and β-pinene, d-limonene, d-citronellol, p-cymene and thymol (Forouzanfar et al., 2014). Other component present in it are p-cymene (7%-15%), carvacrol (6%-12%), 4-terpineol (2%-7%), t-anethol (1%-4%), sesquiterpene longifolene (1%-8%) (Ahmad et al., 2013; Tembhurne et al., 2014).

Seeds contain two different types of alkaloids i.e. isoquinoline alkaloids e.g. nigellicimine and nigellicimine-N-oxideand pyrazol alkaloids or indazole ring bearing alkaloids which include nigellidine and nigellicine. Moreover, it also contain alpha-hederin, a water soluble pentacyclic triterpene and saponin, a potential anticancer agent (Sultana et al., 2015; Ahmad et al., 2013). Flavonoids present in seed are quercetin and kaempferol 3-glucosyl (1-2) galactosyl (1-2) glusoside and quercitin–3-(6-ferulolyl glucosyl) (1-2) galactosyl (1-2) glucoside (Merfort et al., 1997). Other than those triglycoside quercetin 3-glucoside, kaempferol 3-glucoside and rutin were also isolated from the seeds of N. sativa (Tembhurne et al., 2014).

The nutritional component of seeds contain protein (26.7%), fat (28.5%), carbohydrates (24.9%), crude fibre (8.4%) and total ash (4.8 %), vitamins and minerals like potassium, phosphorus, sodium, iron are main element and Copper, Magnesium, Manganese. Zinc and Calcium found at low levels (AI-Jassir., 1992; Sultana et al., 2015). The seeds contain carotene which is converted by the liver to vitamin A. Root and shoot are reported to contain vanillic acid (Ahmad et al., 2013).

The fixed oil comprise of unsaturated fatty acids which includes: arachidonic, eicosadienoic (3%), linoleic (50-60%), linolenic, oleic (20%) (Sultana et al., 2015) and saturated fatty acid comprise of palmitic (12.5%), stearic and myristic acid (Tembhurne et al., 2014; Nickavara et al., 2003). Beta-sitosterol, cycloeucalenol, cycloartenol, sterol esters and sterol glucosides are also found (Forouzanfar et al., 2104). α-sitosterol is a major sterol, which accounts for 44% and 54% of the total sterols in Tunisian and Iranian varieties of N. sativa oils, pursued by stigmasterol (6.57-20.92% of total sterols) (Sultana et al., 2015).

Numerous chemical components reported are nigellone, avenasterol-5-ene, nigellone, nigellicine, nigellimine, nigellimine-N-oxide,avenasterol-7-ene,campesterol, cholesterol, citrostadienol, lophenol, obtusifoliol, stigmastanol, stigmasterol-7-ene, β-amyrin, butyro- spermol, cycloartenol, 24-methylene-cycloartanol, taraxerol, tirucallol, 3-O-[β-D-xylopyranosyl(1→3)-α-L-rhamnopyranosyl(1→2)-α-L-arabinopyranosyl]-28-O-[α-L-rhamnopyranosyl(1→4)-β-D-glucopyranosyl(1→6)-β-D-gluco-pyranosyl] hederagenin, volatile oil (0.5-1.6%), fatty oil (35.6-41.6%), oleic acid, esters of unsaturated fatty acids with C-15 and higher terpenoids, esters of dehydrostearic and linoleic acid, aliphatic alcohol, melanthin, melanthigenin, bitter principle, tannin, resin, protein, reducing sugar, glycosidal saponin, 3-O-[β-D-xylopyranosyl-(1→2)-α-L-rhamno-pyranosyl-(1→2)-β-D-glucopyranosyl]-11-methoxy-16, 23-dihydroxy-28-methylolean-12-enoate,stigma-5, 22-dien- 3-β-D-gluco-pyranoside,cycloart-23-methyl-7, 20, 22- triene-3β, 25-diol, nigellidine-4-O-sulfite, N. mines A3, A4, A5, C, N. mines A1, A2, B1, andB2 (Sultana et al., 2015; Ahmad et al ., 2013; Paarakh et al., 2010).

Traditionally seed of N. sativa are used in middle-eastern folk medicine for treating several diseases for more than 2000 years (Forouzanfar et al., 2014). There is extensive historical description of folklore usage of N. sativa seeds and their oil in Indian and Arabian civilization as food and medicine (Ahmad et al., 2013). The seeds were used as pungent appetizer, aromatic, thermogenic, diuretic, expectorant, purgative, anthelmintic, emmenagogue, antibacterial, anti-inflammatory, anodyne, febrifuge, galactagogue stimulant, sudoriferous, sedative and carminative (Sala, 1997). It is used for treatment of wide range of disease conditions related to respiratory system, digestive tract, kidney and liver function, cardiovascular system, skin care, fertility and immune system as well as for general health(Ahmad et al., 2013; Aklaque, 2018; Phulwaria, 2018). Roasted seeds are given internally to stop the vomiting (Ahmad et al., 2013; Sultana et al., 2015).

In Indian and Arabian system of medicine, seeds are used for skin diseases, jaundice, gastrointestinal problems, anorexia, conjunctivitis, diarrhea, dyspepsia, rheumatism, diabetes, hemorrhoids, helminthiasis, hypertension, halitosis, intrinsic hemorrhage, paralysis, amenorrhea, dysmenorrhea anorexia, asthma, cough, bronchitis, headache, fever, influenza and eczema (Forouzanfar et al., 2014; Sala, 1997; Kirtikar, 1987). It is also traditionally used by Iranian therapists as a treatment for mastalgia (Aklaque, 2018).

In case of skin eruptions, seeds powder are mixed with sesamum oil for local application (Kirtikar, 1987). Externally the oil is used as an antiseptic and local anesthetic. Due to its countless uses nigella has earned the Arabic approbation of ‘Habbat ul Barakah’, meaning the seed of blessing (Ahmad et al., 2013; Phulwaria, 2018).

It is generally used to increase lactation in nursing mothers, to fight against parasitic infections, and to boost their immune system. Since they have very low level of toxicity seeds are also used in food like flavoring additive in the breads and pickles (Sultana et al., 2015).

표-사무실입력

There is a prevalent use of herbal drug as traditional medicine and is gaining global popularity. One of them is N. sativa which have been used since antiquity as a natural therapy for various diseases and also their use were stated in Bible, Tibb-e-Nabwi, Cannon of Medicine and Ayurvedic literature. A lot of studies validate its significance in folk medicine as antihypertensive, anti-inflammatory, immune stimulant, analgesic, anti-microbial, anti-fungal, anti-oxidant, and as an anti-cancer. Further work can be desired to discover the pharmacokinetics, biochemical and therapeutic activities of active constituents and their collaboration with modern drugs. Cellular and molecular target of various constituent of N. sativa seed may be explored to get more effective and safer drug. Further thorough Clinical studies on N. sativa should be done so that humanity can be benefited.