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Journal of Drug Delivery and Therapeutics
Open Access to Pharmaceutical and Medical Research
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Open Access Full Text Article Review Article
A Comprehensive review of Nigella sativa (kalonji) from the Unani perspective
Mahboob Alam1, Shabir Ahmad Bhat2, Shameem Ahmad Rather3, Naseer Ahmed Hakeem 4, Abdul Khalique5, Sana Mobin1, Fauzia Azmi1, Zamal Mariyam 1
1 M.D Scholar, Dept of Moalajat, Regional Research Institute of Unani Medicine, University of Kashmir, Srinagar, India
2 Assistant Professor, Dept. of Moalajat, Regional Research Institute of Unani Medicine, University of Kashmir, Srinagar, India
3 Professor, Department of Moalajat, Regional Research Institute of Unani Medicine, Naseem Bagh, University of Kashmir, Srinagar, Jammu and Kashmir, India
4 Director, Unani and Panchakarma Hospital, Srinagar, Kashmir, India
5 Lecturer, Dept of Ilmul Atfal, State takmeel ut tib College and hospital, Lucknow, India
|
Article Info: _____________________________________________ Article History: Received 24 July 2023 Reviewed 07 Sep 2023 Accepted 26 Sep 2023 Published 15 Oct 2023 _____________________________________________ Cite this article as: Alam M, Bhat SA, Rather SA, Hakeem NA, Khalique A, Mobin S, Azmi F, Mariyam Z, A Comprehensive review of Nigella sativa (kalonji) from the Unani perspective, Journal of Drug Delivery and Therapeutics. 2023; 13(10):121-128 DOI: http://dx.doi.org/10.22270/jddt.v13i10.6239 _____________________________________________ *Address for Correspondence: Mahboob Alam, M.D Scholar, Dept of Moalajat, Regional Research Institute of Unani Medicine, University of Kashmir, Srinagar |
Abstract _____________________________________________________________________________________________________________________ The remarkable therapeutic properties of Nigella sativa, often known as black seed or kalonji are well recognized. The use of N. sativa seeds and its oil has a long history in various traditional food and medical systems. As stated by the holy prophet of Islam (PBUH), Shoneez is important since it can cure all diseases with the exception of death. It is widely used in several conventional medical systems, including Unani Tibb, Chinese medicine, Ayurveda, and Siddha. The goal of the current review is to provide a thorough overview of the literature on scientific studies of the pharmacognostical properties, chemical makeup, and pharmacological activity of the seeds of this plant. The data was collected from various reputed data bases like PubMed, Science direct, Web of Saciences, Google Scholar and Research Gate. The traditional and Unani literature was also searched from the classical books of Greco-Arab medicine in addition to other digital sources. According to traditional Unani literature, N. sativa exhibits a variety of pharmacological properties, including those that are carminative, anti-inflammatory, analgesic, diuretic, emmenagogue, galactagogue, and expectorant. Numerous phytochemical, pharmaceutical, and clinical studies have been conducted on N. sativa, revealing its potential anti-diabetic, anti-cancer, immunomodulator, analgesic, antimicrobial, anti-inflammatory, bronchodilator, renal protective, gastro-protective, antioxidant, and other properties. N. sativa is among the top-ranked evidence-based herbal medications because of its remarkable healing ability. The main bioactive component of the essential oil, thymoquinone, is responsible for the majority of its medicinal capabilities. Nigella sativa is a potent herb which exhibits wide range of pharmaceutical properties, most of which have been confirmed via preclinical and clinical studies. This review may thus be useful for the research community in particular and common people in general to avail the benefits of N. sativa. Keywords: Anti-cancer, Kalonji, Habat-ul-Sauda, Shoneez, Thymoquinone, Nigella sativa, Unani |
Introduction:
Kalonji, a well-known herbal remedy also known as black seed or black cumin, has a rich medicinal value. It is used to treat various degenerative disorders. In botanical terms, it is referred to as Nigella sativa Linn (F - Ranunculaceae). It is one of the magnificent herbs with a rich historical and religious past. 1,2
Various indigenous and traditional medical systems have been using medicinal plants to heal illnesses for many years. N. sativa is a dicotyledonous miraculous herb of the rananculaceae family. 3,4
Taxonomical classification:
Kingdom: Plantae
Subkingdom: Tracheobionta
Super division: Spermatophyta
Division: Magnoliophyta
Class: Magnoliopsida
Order: Ranunculales
Family: Ranunculaceae
Genus: Nigella L.
Species: N. sativa
In Unani literature it is described in the name of Habat-ul-Sauda 5
Among various medicinal plants, Nigella sativa (N. sativa) (family Ranunculacae) is emerging as a miracle herb with a rich historical and religious background since many researches revealed its wide spectrum of pharmacological potential. N sativa is commonly known as black seed. n sativa is native to southern europe, north africa and southwest asia and it id cultivated in many countries in the world like middle eastern mediterranean region, south europe, india, pakistan, syria, turkey, soudia arabia. 6,7
Since ancient times, N. sativa seeds and oil have been widely utilised to cure a wide range of illnesses all throughout the world. Additionally, it is a key medication in the conventional Indian medical system, alongside Unani and Ayurveda.2,3,8
Vernacular name: 9,10,11,12,13,14,15,16,17
Arabic: Habbatul Sauda, Kabodan, Kamun Aswad, Shoneez
Persian: Shoneez, Siyah Dana
Urdu: Kalonji
Hindi: Kalonji, Kalajira, Mangraila
English: Small Funnel, Black Cumin
Bengali: Kala Zeera, Mangrela
Gujrati: Kalaunji Jirum, Kadujeeroo
Kannada: Karijirige
Marathi: Kalaunji-jire, kalerjire
Malyalam: Karinchirakam
Telugu: Peeajila Kara, Nallajilakara
Panjabi: Kavanji
Tamil: Karunjarakam, Karunjiragam
Sanskrit: Susavi, Krishna jiraka, Upakuncika, Karvi, Sthula
Jiraka
Turki: Qarachurak Audi
Unani: Sino, Sheenon, Kamaazaruus
Sindhi: Kalodi
Unani Description:
Properties Temperament (Mizaj): 4
Hot2, Dry2
Hot3, Dry3
Taste (Maza): 4
Slightly bitter
Acrid in taste
Odour (Boo): 4
Pleasant odour like a lemon
Strong smell
Substitute (Badl): 4
Olea europeae (Samaghe zaitoon)
Lepidium sativum (Tukhme Rashaad)
Pimpinella anisum (Anisoon)
Anethum sowa (Sowa Seed)
Hyoscyamus niger (Ajwain Khurasani Seed)
Adverse Effect (Muzir): 4
It affects liver
cause diphteria
harms kidney
lungs and patient with headache
Main Function (Nafa-e-Khas): 4
Diuretic and Emmenagogue (Mudir-e-Baul wa Haiz)
and Jaundice (Yarqaan)
Abortificient (Mukhrij-e-Janeen), Haemerrhoids (Bawaseer)
Corrective (Musleh): 4
Cucumis sativus (Tukhme Khyaar)
Sterculia urens (Kateera)
Drugs of cold temperament (Sard Ashiyaa)
Bumbusa arundinacea (Banslochan)
Vinegar (Sirka)
Cichorium intybus (Kasni)
Important Unani formulations: 4
Habb-e-Hilteet, Jawarish Shoneez, Majoon Kalkalanaj Majoon Fanjnosh, Majoon Kundur
Uses of Kalonji in Therapy and Activities: 3,5,10,18,19,21,22,23,24
Therapeutic uses of kalonji can easily be understood from the Table 1 as given below:
Table 1: Therapeutic Uses of Kalonji
|
Munzij (Coctive), |
Nazla (Cold) |
|
Jali (Detergent), |
Skin diseases (Amraz e jild), Bars (Vitiligo) |
|
Mushtahi (Appetizer), |
Zof e Isthiha (Loss of Appetite) |
|
Muqawwi Jigar (Liver Tonic) |
Amraz-e-kabid (Ailments of liver), Yarqan (Jaundice) |
|
Hazim (Digestive) |
Su-e-hazm (Dyspepsia) |
|
Musakkin e Alam (Analgesic) |
Asabi dard (Neuralgia), Qulanj (Colic) |
|
Mudir-e-tams (Emmenagogue), |
Ehtebas-e-tams (Amenorrhoea) |
|
Mudir-e-baul (Diuretic), |
Qillat-e-baul (Oligouria) |
|
Qatil-e- kirm Shikam (Anthelmintic) |
Kirm Shikam (Worms infestation) |
|
Muqawwi-e-meda (Stomachic) |
Zof-e-meda (Weakness of stomach) |
|
Kasir-e-riyah (Carminative), |
Nafakh-e-shikam (Flatulence) |
Characteristics of Pharmacology:
1. Morphology of the plant: An important Indian medicinal crop called kalonji is grown mostly in the northern Indian states of Panjab, Himachal Pradesh, Bihar, and Assam, with sporadic cultivation also taking place in Assam. 10,13,25,27
N. sativa is an annual blooming plant that reaches heights of 20 to 90 cm. It has finely divided leaves with leaf segments that range in width from narrowly linear to threadlike. The fragile, 5-10 petaled blossoms are typically white, yellow, pink, pale blue, or pale purple in colour. The fruit is a sizable, inflated capsule made up of 3–7 connected follicles, each of which is filled with several seeds. 2,6,27
2. Characteristics of the seeds and powder: The seeds are small, dicotyledenous, trigonus, angular, regular-tuberculer, 2-3.5 mm * 1-2 mm, outwardly black and internally white, with a faintly aromatic and somewhat bitter odour. Transverse section of the seed, viewed under a microscope, reveals a single-layered epidermis made up of elliptical, thick-walled cells that are outwardly coated by a papillose cuticle and internally filled with dark brown material. When seen under a microscope, parenchymatous cells and oil globules are visible in the seed powder.6,7,27
Chemical constituents:
Thymoquinone is the active ingredient in kalonji. 28,29
The seeds produced a yellowish-brown volatile oil with a foul aroma after steam distillation.11,29
Essential oil, Volatile oil, Fixed oil, Steroid, Saponin, Melanthin, Mucilage, Resins, Sugars, Alkaloids, Tannins, Linoleic acid, Palmitic acid, Stearic acid, Palmitoleic acid and Oleic acid, Nigellidine, Nigellicine, Dithymoquinone, Iron, Copper, Zinc, Phosphorus, Calcium. 13,15,17,30
Scientific studies:
The main chemical compounds are thymoquinone (30%-48%), thymohydroquinone, dithymoquinone, p-cymene (7%-15%), carvacrol (6%-12%), 4-terpineol (2%-7%), tanethol (1%-4%), sesquiterpene longifolene (1%-8%), -pinene, and thymol, among others. Additionally, alpha-hederin, a water-soluble pentacyclic triterpene, and saponin, a possible anticancer compound, are present in Kalonji (Kalonji) seeds. 6,24
The chemical constituents found in Kalonji seeds have been described in table 2 as given below:
Table 2: Chemical constituents of Kalonji
|
Protein: |
(26.7%) |
|
Fat: |
(28.5%) |
|
Carbohydrate: |
(24.9%) |
|
Crude Fibre: |
(8.4%) |
|
Total ash: |
(4.8 %) |
|
Vitamins and minerals: |
Cu, P, Zn and Fe etc [15,40] |
|
Saturated fatty acids: |
(30% or less) |
Fatty oil rich in unsaturated fatty acids, mainly linoleic acid (50-60%), oleic acid (20%), eicodadienoic acid (3%) and dihomolinoleic acid (10%). 24,31,32,33
Nephroprotective activity: One of the studies was performed to examine the immunomodulatory and protective effects of Nigella sativa L. against renal tissue damage in mice with Pristane-induced lupus (PIL). The outcomes demonstrated that the Nigella sativa L. group had the lowest levels of Interleukin (IL) (IL-17, IL-6, and IL-23) expression. The Nigella sativa L. group had the lowest and most-near-normal renal damage, according to histological analysis. It has thus been found that Nigella sativa L. has an immunomodulatory impact and can protect mice given PIL from kidney damage. We advise that additional study on the use of Nigella sativa L. as a supplementary supplement in lupus patients be taken into consideration.34
A study found that gentamicin (GM)-related nephrotoxicity in rabbits was protected by the nephro-protective effects of vitamin C and Kalonji oil. Indicators of nephrotoxicity for all the rabbit groups included serum creatinine, blood urea nitrogen, and antioxidant activity. It was discovered that both Kalonji oil and vitamin C had nephroprotective effects since they reduced serum creatinine, blood urea nitrogen, and antioxidant activity as compared to results from the GM control group. They demonstrated a synergistic nephroprotective effect when these two antioxidants were administered together. 24,35
Antidyslipidemic activity:
According to reports, Kalonji proved quite effective in treating dyslipidemia in 20 patients when given in the amount of 1gm in Safoof (powder) form twice day for 60 days. 17,36
According to a different study, kalonji has an antiatherogenic impact by lowering the amount of low-density lipoprotein cholesterol and increasing high-density lipoprotein. level. 17,37
500 mg of kalonji seed powder taken with a statin (10–20 mg) is the recommended dosage for this group. The addition of Nigella sativa results in a significant (P0.05) reduction in cholesterol, LDL, VLDL, and triglycerides as well as a significant increase in HDL. Thus, it decreased a risk factor for coronary artery disease. 17,38
Hypoglycaemic activity:
According to reports, following 14 days of therapy, Wistar rats' fasting blood glucose levels decreased significantly (p0.01) to 61.3% when given the aqueous extract of kalonji powder at a dose of 500 mg/kg body weight. 17,39
According to a study conducted on 40 diabetic patients, Nigella sativa can be used as an additional medication therapy for metabolic syndrome patients who have poor glycemic control and were found to be a safe and efficient treatment for those with the condition. 17,40
According to another study, treatment with N. sativa (5 mg/kg b.w.) dramatically boosted body weight gain and significantly (p0.001) decreased fasting blood glucose levels compared to the control. Histopathological analysis revealed that N. sativa (5 mg/kg b.w.) significantly preserved pancreatic islet cells and partially regenerated the hepatic glycogen content. When compared to the control, the number of islets, cells, and islets diameter were determined to be statistically significant (p0.01, p0.05). 17,41
In a study, which was conducted to determine the effects of Kalonji (N. sativa) seed ethanol extract on insulin secretion in INS832/13 and β TC-tet lines of pancreatic β-cells and on glucose disposal by C2C12 skeletal muscle cells and 3T3-L1 adipocytes. Treatment with Kalonji (N. sativa) increased glucosestimulated insulin secretion by more than 35% without affecting sensitivity to glucose. The treatment also accelerated β-cell proliferation. Kalonji (N. sativa) increased basal glucose uptake by 55% in muscle cells and approximately 400% in adipocytes. It is concluded that in vivo. Anti hyperglycemic effects of Kalonji (N. sativa) seed extract are attributable to a combination of therapeutically relevant insulinotropic and insulin-like properties. 17,42
In another study, it was found that effect of the seeds of Kalonji (N. sativa) have glucose lowering effect in rats. Further study on the plant mixture containing Kalonji (N. sativa) revealed that the blood glucose lowering effect was due to the inhibition of hepatic gluconeogenesis and the plant extract mixture may prove to be useful therapeutic agent in the treatment of non-insulin dependent diabetes mellitus. 17,43
Anticancer activity:
It has been shown that N. sativa's methanolic extract significantly inhibits the growth of the cancer cells HL-60 and U-937, with IC50 values of 13.70 g/ml and 28.31 g/ml, respectively.17,44
Another study shown that the essential oil of Nigella sativa prevents or delays metastasis by rapidly reducing the volume of the initial tumour at the site of induction in mice. 17,45
In a different investigation, ethanolic extract of N. sativa shown anticancer efficacy in mice with the ehlrich ascites tumour. 17,46
Another study used tumour cell lines, fibrosarcoma, murine, and squamous cell carcinoma to demonstrate the anticancer effect of thymoquinone and thymohydroquinone. 24,47
Thymoquinone and diosgenin together dramatically decreased tumour volume and mass and enhanced apoptosis in a mouse xenograft model. 24,48
The cytotoxicity assay indicated that (biologically synthesized nano thymoquinone) Tb NPs may have anticancer action at concentrations that are much lower than those of (chemically
synthesized nano thymoquinone) Tc NPs. These (nano-thymoquinone) nTQ particles also demonstrated antibacterial activity, eliminating the possibility of bacterial and fungal infections through an expanded zone of inhibition. The findings indicated that the biosynthesized nTQ had more activity due to its capacity to reduce the risk of microbial infections and boost cancer cell death. These results might support the usage of the nTQ biosynthesis method rather than the chemosynthesis method. N. sativa seeds are an excellent and affordable option for both medical treatments and natural food additives. When compared to pure chemical approaches, the currently used procedure is straightforward, secure, affordable less expensive, environmentally friendly, and harmless. The cytotoxicity of the cell line and the antibacterial activity for biological and chemical techniques were also examined in this study, and the results demonstrated that the biological (Thymoquinone) TQ had improved or was on par with synthetic chemical activity in terms of activity. As a result, this work creates new prospects for the efficient conversion of natural chemicals into nanoparticles, which is beneficial for a variety of applications. Our study's findings may have intriguing applications as food additives and other biological medication compositions. 49
Antibacterial activity:
The antibacterial efficacy of the crude Kalonji (N. sativa) extracts against diverse bacterial isolates, including 16 gramme negative and 6 gramme positive samples, was examined. Multiple antibiotic resistances, particularly against gram-negative drugs, were present in this strain. Raw Kalonji (N. sativa) extracts appeared to have some effect on a few of the test organisms. The water and crude alkaloid extracts were the most useful extracts. More gram-negative isolates than gram-positive ones were impacted. 24,43,50
In a study, it was discovered that N. sativa, a phytogenic additive, may replace (Bacitracin methylene disalicylate) BMD, a common in-feed antibiotic, to improve grill performance, particularly when the birds are at risk of necrotizing enteritis. 51
Dermatological effects of Nigella sativa:
Anti-fungal activity:
Another study found that the methanolic Kalonji (N. sativa) extracts had a potent antifungal impact on various strains of Candida albicans. Candida albicans colonies were created in the liver, spleen, and kidneys via an intravenous inoculum. Mice treated with the plant extract 24 hours after the inoculation had a significant inhibition of the organism's growth in all organs under investigation. Additionally, it has been noted that Kalonji (N. sativa) aqueous extract inhibits the development of candidiasis in mice. 24,52
In another study at a dosage of 1 mg/ml, thymoquinone, thymohydroquinone, and thymol also showed antifungal activity against a variety of clinical isolates, including dermatophytes, moulds, and yeasts. 53,54
Wound healing:
Moreover, ether extract of N. sativa seed applied topically onto staphylococcal-infected skin in mice enhanced healing by reducing total and absolute differential WBC counts, local infection and inflammation, bacterial expansion and tissue impairment. 54,55
In Psoriasis:
By using a mouse tail model for psoriasis and the sulforhodamine B assay with human keratinocyte cell lines HaCaT, the ethanolic extract of N. sativa seed was assessed for antipsoriatic activity in both vivo and in vitro. The ethanolic N. sativa extract resulted in significant epidermal differentiation. 54,56
In Vitiligo:
Patients who applied N. sativa oil to their vitiligo lesions twice daily for six months saw a significant decline in the vitiligo area scoring index with no adverse side effects.54,57
In Acne vulgaris:
In a clinical study, after two months of treatment, N. sativa oil lotion 10% significantly decreased the mean lesion count of papules and pustules. In the test group, 58% of patients had a good response to treatment, 35% had a moderate response, and 7% had none at all. Patients' satisfaction with their care was found to be full in 67% of cases, partial in 28% of cases, and nonexistent in 5% of cases. In contrast, the lesions in the control group did not significantly shrink after two months, and only 8% of them responded favourably to treatment, 34% responded moderately, and 58% did not respond at all. In this group, 8% of patients reported complete, 24% partial, and 68% no satisfaction with their treatment. The 10% N. sativa oil lotion group saw no negative side effects. The antibacterial, immunomodulatory, and anti-inflammatory properties of N. sativa oil, according to the scientists, were responsible for the outcomes. 54,58
In Skin cancers:
The authors hypothesised that thymoquinone could be an immunotherapeutic drug that could be used not only as an adjuvant therapy for melanoma but also in the management and prevention of metastatic melanoma. 6,54
Antibacterial:
When used as a side-effect-free treatment for newborns with staphylococcal pustular skin infections, N. sativa extract produced outcomes that were nearly identical to those of topical mupirocin. 54,59
Topozada et al. (1965) were first to report the antibacterial effect of the phenolic fraction of N. sativa oil. 54,60
Antiviral activity:
In a study, Zafar et al. discovered that in healthy volunteers, Kalonji (N. sativa) helped to improve the ratio of helper T cells (T4) to suppressor T cells (T8) and boosted natural killer (NK) cell activity. The human immune deficiency virus protease is inhibited by Kalonji (N. sativa) extract as it boosts immunity, however the active principle(s) responsible for this activity have not been discovered. 24,61,62,63
Immunomodulatory activity:
In a study, the immune-suppressing and cytotoxic effects of the volatile oil from Kalonji seeds were examined in a Long-Evans rat model created to assess the impact of Kalonji seeds on certain immunological components with a particular antigen (typhoid TH). According to the findings, typhoid vaccination-induced antibody production was reduced by nearly twofold after treatment with kalonji oil. 24,64
It has been shown that Nigella sativa's aqueous extract significantly and dose-responsively increases splenocyte proliferation. Additionally, Nigella sativa's aqueous extract encourages splenocytes to secrete Th2 cytokines rather than Th1 cytokines. The aqueous extract of Nigella sativa considerably reduces the release of IL-6, TNFalpha, and NO by primary macrophages; this suggests that Nigella sativa has anti-inflammatory actions in vitro. 65
Thus, it is clear that NS plays a key role in modulating immune system® which can further be elicited by the following research. 66
In a study published in 2004, Nazrul Islam et al. [80] investigated the immunosuppressive and cytotoxic effects of NSEO (Nigella sativa essential oil) in a rat model. After giving NSEO and typhoid antigen injections to Long-Evans rats for 30 days, the authors examined peripheral immune cells (lymphocytes, monocytes, neutrophils, and eosinophils), as well as serum immunoglobulins. The experimental animals' neutrophil counts were markedly reduced by NSEO while their lymphocyte and monocyte numbers were elevated. Serum immunoglobulin levels dropped in animals receiving NSEO treatment. 67,68
In this study it was demonstrated that essential oil sourced from Nigella sativa seeds has a potential proapoptotic and antiproliferative effect on human T lymphocytes in vitro. TQ, one of the NSEO components, may be responsible for these properties. However, it should be emphasized that there is only a few percent of the TQ in NSEO. So TQ is probably not the only one responsible for such strong immunomodulatory properties of NSEO. Meanwhile, even though p-cymene seems to have some pronecrotic properties, at the same time, it at least partially counteracts some of the effects of TQ. Our results could explain the immunosuppressive effect of NS seeds, extracts, or oils in patients suffering from diseases resulting from hypersensitivity reactions, like asthma or rheumatoid arthritis, but adverse skin reactions in other patients after applying the oil. Therefore, additional studies are necessary to determine in what form NS can be used safely in patients suffering from allergic or autoimmune diseases. In previous work, we tested the immunomodulatory effect of Nigella sativa (NS) fatty oil. Our results demonstrated that unrefined, obtained by cold pressing black cumin seed oil inhibited lymphocytes’ proliferation and induced their apoptosis in a dose-dependent manner. In this study, we examined the immunomodulatory properties of essential oil (EO) obtained from the NS seeds by hydrodistillation and its two main constituents: thymoquinone (TQ) and p-cymene. We analyzed the proliferation, activation phenotype, and apoptosis rates of human T lymphocytes stimulated with an immobilized monoclonal anti-CD3 antibody in the presence of serial ethanol dilutions of tested oil or serial distilled water dilutions of tested compounds with flow cytometry. Our results showed that NSEO significantly inhibited the proliferation of CD4+ and CD8+ T lymphocytes, induced cell death in a dose-dependent manner, and reduced the expression of CD28 and CD25 antigens essential for lymphocyte activation. TQ inhibited the proliferation of T lymphocytes and induced cell death, particularly in high concentrations. Meanwhile, p-cymene did not influence lymphocyte proliferation. However, its high concentration induced cell necrosis. These results show that the essential oil from Nigella sativa has powerful immunomodulatory properties, which, at least partially, are related to the TQ component. 69
Cardiovascular activity:
In a different investigation, the effects of Kalonji (N. sativa) and its active ingredient thymoquinone on the heart and arterial blood pressure of rats under anaesthesia were assessed. The arterial blood pressure and heart rates are decreased by both drugs in a dose-dependent manner. Atropine dramatically counteracted these effects, mostly by activating muscarinic and 5-hydroxytryptaminergic mechanisms. These results were statistically comparable to those of the widely used hypertension medication nifedipine. It was determined that the drug's effects were partially attributable to its diuretic action, which was equivalent to frusemide. 24,70
Contraceptive and anti-fertility activity:
In a study, it was discovered that oral administration of hexane extract of kalonji seeds at a concentration of 2 g/kg daily on days 1 through 10 postcoitum prevented pregnancy in experimental rats. 24,71
Hepato-protective activity:
In a different study, male Wistar rats were given an aqueous extract of kalonji seeds to test for hepatoprotective efficacy against carbon tetrachloride-induced hepatotoxicity. To ascertain the hepatoprotective potential, many biochemical variables were examined. A substantial hepatoprotective effect against carbon tetrachloride-induced liver damage was seen in the aqueous extract, demonstrating the presence of hepatoprotective action. 24,72
Gastro-protective activity:
In a study, the anti-ulcer potential of Kalonji (N. sativa) aqueous suspension was investigated on experimentally induced gastric ulcers and basal gastric secretion in rats. It was discovered that Kalonji has an anti-ulcer effect due to its antioxidant and anti-secretory activities, which may be prostaglandin-mediated. 24,73
Antioxidant and antiarthritic activity:
In a study, it was evaluated that thymoquinone component of Kalonji (N. sativa) showed the antioxidant and antiarthritic activity in Wistar rat by collagen induced arthritis. Oral administration of thymoquinone significantly reduced the levels of pro-inflammatory mediators [IL-1β, IL-6, TNF-α, IFN-γ and PGE (2)] and increased level of IL-10. 24,74
Anti-allergic activity:
In a study, the thymoquinone dimer "Nigellone," which was extracted from the volatile oil of Kalonji (N. sativa), effectively reduced symptoms in individuals with bronchial asthma without causing any harm. 64
Patients with allergic conditions such as allergic rhinitis, atopic eczema, and bronchial asthma who received kalonji oil had lower immunoglobulin E and eosinophil counts. 24,75
In allergic rhinitis:
In a study Nigella sativa oil was aimed to compare with mometasone furoate, a topical steroid, on a rat model in the prevention of allergic rhinitis symptoms, in which total of 28 numbers 2-4 months-old Wistar Hannover rats weighing 250-350 gm was randomly divided into four groups of seven, which included control, allergic rhinitis, mometasone furoate, and Nigella sativa oil groups. Loss of cilia, an increase of goblet cells, vascular proliferation, inflammatory cell count, eosinophil infiltration, and the degree of hypertrophy in chondrocytes were assessed by light microscopy. According to the findings obtained from this study, it was found that anti-inflammatory and anti-allergic effects of Nigella sativa oil as equally effective as mometasone furoate in the treatment of experimentally generated allergic rhinitis. 76
Adjunctive intervention in obesity management: or as a beneficial dietary element in treating obesity and associated issues:
In this study, N. sativa supplementation may have advantages in lowering body composition indicators that increase BW (body weight) and BMI (body mass index). Sensitivity analysis revealed the positive effects of N. sativa supplementation on waist and hip circumference. It might be recommended as a beneficial dietary element for treating problems like obesity. In addition, it is advised to take supplements for about 8 weeks of treatment. Overall, this study's findings are in favour of using N. sativa supplements as an additional weight-management strategy. When compared to the placebo group, N. sativa treatment dramatically decreased BW and BMI. However, no appreciable drops in WC (waist circumference), HC (hip circumference), or WHR (waist-hip ratio) were identified. According to the current meta-analysis, supplementing people with N. sativa significantly reduced their body weight and BMI but not their WC, HC, or WHR. As a result of our findings, N. sativa supplementation is suggested as an additional strategy in the management of obesity. 77
Conclusion:
N. sativa is clearly potent herb which exhibits wide range of pharmaceutical properties, most of which have been confirmed via preclinical studies & only a small portion has been evaluated through randomized clinical trials. This review may thus be useful for the research community in particular and common people in general to avail the benefits of N. sativa
Conflict of interest: None
Funding: None
Author contribution:
Study design: Mahboob Alam, Shabir Ahmad Bhat
Data collection: Mahboob Alam
Drafting of manuscript: Mahboob Alam, Shabir Ahmad Bhat
Critical revision: Mahboob Alam, Shabir Ahamd bhat, Shameem Ahmad Rather
Abbreviation: BW (body weight), BMI (body mass index), WC (waist circumference), HC (hip circumference), N. Sativa (Nigella Sativa), TQ (thymoquinone), EO (essential oil), NSEO (Nigella sativa essential oil).
References:
1. Ahmad W, Khan RM, Zeenat F, et al. Therapeutics, phytochemistry and pharmacology of an important Unani drug kalonji (Nigella sativa Linn): A review. European journal of pharmaceutical and medical research. 2017; 4(7):329-346
2. Goreja WG, Black Seed: Nature’s Miracle Remedy. Amazing Herbs Press, New York, 2003.
3. Ahmad A, Husain A, Mujeeb, M., et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pacific Journal of Tropical Biomedicine. 2013;3(5):337-52. https://doi.org/10.1016/S2221-1691(13)60075-1
4. Areefa A, Mohd A, Shah CS, A Review om Nigella sativa (Kalonji) Seeds: A Universal Healer. CELLMED. 2020;10(2):11.1-11.14. https://doi.org/10.5667/CELLMED.2020.0011
5. Ghani N, Khazainul Advia. Idara Kitab Us Shifa, 2010; pp. 1061-1062.
6. Ahmad I, Muneer KM, Tamimi IA, Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome. Toxicol Appl Pharmacol. 2013;270(1):70-76 https://doi.org/10.1016/j.taap.2013.03.027.
7. Khare CP, Encyclopedia of Indian medicinal plants. Springes-Verlag Berlin Heidelberg, New York, 2004.
8. Sharma PC, Yelne MB, Dennis TJ, Database on medicinal plants used in Ayurveda. CCRAS, New Delhi. 2005; pp. 420-440.
9. Anonymous, Medicinal Plants of India. Vol.2. ICMR, New Delhi. 1987; pp. 337-40.
10. Anonymous, Standardization of Single Drug of Unani medicine. Part 2. CCRUM, New Delhi. 1992; pp. 196-200.
11. Anonymous, The Unani Pharmacopeia of India.Vol.1. New Delhi. 2007; pp. 42-43.
12. Das PN, Kumar U, Agros’s Dictionary of Medicinal Plants, Jodhpur. 2005; pp. 226.
13. Khare CP, Indian Medicinal Plants. Springer Science, New Delhi. 2007; pp. 439.
14. Nadkarni KM, Indian Materia Medica, Vol. 1. Popular Prakashan Private Limited Mumbai. 1982; pp. 854-57.
15. Nadkarni KM, Indian Plants and Drugs. Srishti Book Distributers, New Delhi. 2005; pp. 259-60.
16. Pullaiah T, Encyclopaedia of World Medicinal Plants, Regency Publication, New Delhi. 2006; Vol. 3, pp. 1409.
17. Shamim Ahmed, Alam A, Ahmad Z, Shoneez (Nigella sativa) and its therapeutic effect in Unani Medicine – A Review, International Journal of Pharma Sciences and Research. 2015;6 (1):12-14
18. Baitar AAI, Al Jami ul Mufradat al Adviya wal Aghziya. Vol 4. Central Council for Research in Unani Medicine, New Delhi. 2003; pp. 397-399.
19. Daba MH, Abdel RMS, Hepatoprotective activity of thymoquinone in isolated rat hepatocytes. Toxicol Lett. 1998;95(1):23-29 https://doi.org/10.1016/s0378-4274(98)00012-5
20. Ghaznavi KM, Tibbe-e-Nabvi aur Jadid Science, Al-Faisal Nasheeran wa Tajeera-e- Kutab. Urdu Bazar Lahore, Pakistan. 1991; pp. 228-36.
21. Hakim, MA, Bustanul Mufradat. Idara Kitabul Shifa, Delhi. 2002; pp. 174-175.
22. Hkm Safiuddin; Unani Advia Mufreda. Qaumi Council Farogh Urdu Zaban. pp. 230-231.
23. Kabiruddin M, Makhzan ul Mufradat wa Khawas ul Advia. Siddiqui Publications. Ynm, Lahore, Pakistan. pp. 170-171.
24. Bashir F, Akhtar J, Anjum N, et al. Kalonji (nigella sativa): transformation from herb to multifunctional medicine. Journal of Emerging Technologies and Innovative Research. 2018;5(8):132-141
25. Anonymous, The Wealth of India. raw material. Vol.7. Publication & Information Directorate CSIR. New Delhi. 1997; pp. 63-65, 91-92.
26. Nasir A, Siddiqui MY, Mohsin M, Therapeutic Uses of Shoneez (Nigella sativa Linn.) Mentioned in Unani System of Medicine - A Review, International Journal of Pharmaceutical and Phytopharmacological Research. 2014; 47-49
27. Warrier Pk, Nambiar VPK, Ramankutty C, Indian Medicinal Plants. A Compendium of 500 Species, Orient Longman pvt. Ltd., Madras. 1994; pp. 139-142
28. Amin B, Hosseinzadeh H, Black Cumin (Nigella sativa) and Its Active Constituent, Thymoquinone: An Overview on the Analgesic and Anti-inflammatory Effects. Planta Med. 2016;82(1-2):8-16. https://doi.org/10.1055/s-0035-1557838
29. Sana SH, Ashraf S, Kalonji (Nigella sativa Linn) a comprehensive review on ethnopharmacological properties with special focus on its Unani perspective. International Journal of Unani and Integrative Medicine. 2019;3(2):29-30
30. Anonymous, The useful Plants of India. CSIR. New Delhi. 2006; pp. 399.
31. Bourgou S, Ksouri S, Bellila A, et al. Phenolic composition and biological activities of Tunisian Nigella sativa L. shoots and roots, Comptes Rendus Biologies. 2008;331(1):48-55. https://doi.org/10.1016/j.crvi.2007.11.001
32. Cheikh-Rouhou S, Besbes S, Lognay G, et al. Sterol composition of black cumin (Nigella sativa L.) and Aleppo pine (Pinus halepensis Mill.) seed oils, Journal of Food Composition and Analysis. 2008;21(2):162-168. https://doi.org/10.1016/j.jfca.2007.09.001.
33. Nickavar B, Mojab F, Javidnia K, et al. Chemical Composition of the Fixed and Volatile Oils of Nigella sativa L. from Iran. Zeitschrift für Naturforschung C. 2014;58(9-10):629-631. https://doi.org/10.1515/znc-2003-9-1004
34. Hikmah Z, Endaryanto A, Ugrasena ID, et al. Nigella sativa L. as immunomodulator and preventive effect on renal tissue damage of lupus mice induced by pristane. Heliyon. 2022; 8(4):1-9. https://doi.org/10.1016/j.heliyon.2022.e09242.
35. Saleem U, Ahmad B, Rehman K, et al. Nephro-protective effect of vitamin C and Nigella sativa oil on gentamicin associated nephrotoxicity in rabbits”. Pak J Pharm Sci. 2012;25(4):727–730.
36. Rasheed A, Siddiqui MA, Khan JA. Therapeutic evaluation of Kalonji (Nigella sativa) in dyslipidemia. A Randomized control trial. Medical Journal of Islamic World Academy of Sciences. 2014;22(3):111-116.
37. Bhatti IU, Rahman FU, Khan MA, et al. Effect of prophetic medicine Kalonji (Nigella sativa L.) on lipid profile of human beings: an in vivo approach. World Applied Science Journal. 2009;6(8):1053-1057. http://www.idosi.org/wasj/wasj6(8)/7.
38. Zahida T, Siraj Z, Ahmad N, et al. The effect of Nigella sativa (Kalonji) on lipid profile in patients with stable coronary artery disease in Multan, Pakistan. Pakistan journal of nutrition. 2011;10(2):162-167. https://doi.org/10.3923/pjn.2011.162.167
39. Alam S, Reddy SK, Baig A, et al. Evaluation of anti-diabetic and anti-lipidimic potential of kalongi sugar powder water extract in Streptozocin induced diabetic rats. International Journal of Pharmacy and Pharmaceutical Sciences. 2013;5(1):94-96
40. Najmi A, Nasiruddin M, Khan RA, et al. Therapeutic Effect of Nigella Sativa in Patients of Poor Glycemic Control. Asian Journal of Pharmaceutical and Clinical Research. 2012;5(3):224-228.
41. Alimohammadi S, Hobbenaghi R, Javanbakht J, et al. 2013. Protective and antidiabetic effects of extract from Nigella sativa on blood glucose concentrations against streptozotocin (STZ)-induced diabetic in rats: an experimental study with histopathological evaluation. Diagn Pathol. 2013;8(137):1-7. https://doi.org/10.1186/1746-1596-8-137.
42. Zaoui A, Cherrah Y, Alaoui K, et al. Effects of Nigella sativa fixed oil on blood homeostasis in rat. J Ethnopharmacol. 2002;79(1):23-26. DOI: 10.1016/s0378-8741(01)00342-7.
43. Mohamed AM, EL-Sharkawy FZ, Ahmed SAA, et al. Glycemic Control and Therapeutic Effect of Nigella sativa and Curcuma longa on Rats with streptozotocin-induced Diabetic Hepatopathy. Journal of Pharmacology and Toxicology. 2009;4(2):45-57. DOI: https://doi.org/10.3923/jpt.2009.45.57.
44. Raval BP, Shah TG, Patel JD, et al. Potent anticancer activity of Nigella Sativa Seeds. Archives of Applied Science Research. 2010;2(1):52-56.
45. Ait Mbarek L, Ait Mouse H, Elabbadi N, et al. Anti-tumor properties of blackseed (Nigella sativa L.) extracts. Braz J Med Biol Res. 2007;40(6):839-47. https://doi.org/10.1590/s0100-879x2006005000108.
46. Musa D, Dilsiz N, Gumushan H, et al. Antitumor activity of an ethanol extract of Nigella sativa seeds. Biologia, Bratislava. 2004; 59(6):735-740
47. Hannan A, Saleem S, Chaudhary S, et al. 2008. Anti-bacterial activity of Nigella sativa against clinical isolates of methicillin resistant Staphylococcus aureus. J Ayub Med Coll Abbottabad. 2008;20(3):72-74.
48. Das S, Dey KK, Dey G, et al. 2012. Antineoplastic and Apoptotic Potential of Traditional Medicines Thymoquinone and Diosgenin in Squamous Cell Carcinoma. PLoS ONE. 2012; 7(10): e46641. https://doi.org/10.1371/journal.pone.0046641.
49. Gnanasekaran P, Roy A, Natesh NS, et al. Removal of microbial pathogens and anticancer activity of synthesized nano-thymoquinone from Nigella sativa seeds, Environmental Technology & Innovation. 2021; 24. https://doi.org/10.1016/j.eti.2021.102068.
50. Ma CM, Miyashiro H, Hattori M, et al. Screening of traditional medicines for their inhibitory effects on human immunodeficiency virus protease. J. Tradit. Med. 1994; 11(4): 416-417.
51. Manjunatha V, Nixon JE, Mathis GF, et al. Nigella sativa as an antibiotic alternative to promote growth and enhance health of broilers challenged with Eimeria maxima and Clostridium perfringens. Poultry Science. 2023; 102(8):102831. https://doi.org/10.1016/j.psj.2023.102831.
52. Bita A, Rosu A, Calina D, et al. An alternative treatment for Candida infections with Nigella sativa extracts. European Journal of Hospital Pharmacy: Science and Practice. 2012; 19(2):162. http://dx.doi.org/10.1136/ejhpharm-2012-000074.203
53. Taha M, Azeiz A, Saudi W, Antifungal effect of thymol, thymoquinone and thymohydroquinone against yeasts, dermatophytes and non-dermatophyte molds isolated from skin and nails fungal infections. Egypt. J. Biochem. Mol. Biol. 2010; 28(2):109–126. http://dx.doi.org/10.4314/ejbmb.v28i2.60802.
54. Aljabre SHM, Alakloby OM, Randhawa MA, Dermatological effects of Nigella sativa, Journal of Dermatology & Dermatologic Surgery. 2015; 19(2):92-98. https://doi.org/10.1016/j.jdds.2015.04.002.
55. Abu-Al-Basal MA, 2011. Influence of Nigella sativa fixed oil on some blood parameters and histopathology of skin in staphylococcal infected BALB/c mice. Pak. J. Biol. Sci. 2011; 14(23):1038–1046. https://doi.org/10.3923/pjbs.2011.1038.1046.
56. Dwarampudi LP, Palaniswamy D, Nithyanantham M, et al. Antipsoriatic activity and cytotoxicity of ethanolic extract of Nigella sativa seeds. Pharmacogn Mag. 2012; 8(32)268-72. https://doi.org/10.4103/0973-1296.103650.
57. Ghorbanibirgani A, Khalili A, Rokhafrooz D, Comparing Nigella sativa Oil and Fish Oil in Treatment of Vitiligo. Iran Red Crescent Med J. 2014; 16(6): e4515. https://doi.org/10.5812/ircmj.4515.
58. Abdul-Ameer N, Al-Harchan H, Treatment of acne vulgaris with Nigella Sativa oil lotion. Iraqi Postgraduate Medical Journal. 2010; 9(2):140-144
59. Rafati S, Niakan M, Naseri M, Anti-microbial effect of Nigella sativa seed extract against staphylococcal skin Infection. Med J Islam Repub Iran. 2014; 28(42):1-4
60. Toppozada HH, Mazloum HA, el-Dakhakhny M, 1965. The antibacterial properties of the Nigella sativa l. seeds. Active principle with some clinical applications. J Egypt Med Assoc. 1965; 48: Suppl:187-202.
61. El-Kadi A, Kandil O, Effect of Nigella sativa (the black seed) on immunity. In: Proceedings of the Fourth International Conference on Islamic Medicine, Kuwait. 1986; 344–348.
62. Morsi NM, Antimicrobial effect of crude extracts of Nigella sativa on multiple antibiotics-resistant bacteria. Acta Microbiol Pol. 2000; 49(1):63–74.
63. Zafar K, Noorul H, Nesar A, et al. Pharmacological Activity of Nigella Sativa: A Review. World Journal of Pharmaceutical Sciences. 2016; 4(5):234-241.
64. Torres MP, Ponnusamy MP, Chakraborty S, et al. Effects of thymoquinone in the expression of mucin 4 in pancreatic cancer cells: implications for the development of novel cancer therapies. Mol Cancer Ther. 2010; 9(5):1419-31. DOI:10.1158/1535-7163.MCT-10-0075.
65. Majdalawieh AF, Hmaidan R, Carr RI, Nigella sativa modulates splenocyte proliferation, Th1/Th2 cytokine profile, macrophage function and NK anti-tumor activity. J Ethnopharmacol. 2010; 131(2):268-75. DOI:10.1016/j.jep.2010.06.030
66. Bhat SA, Rather SA, Iqbal A, et al. Immunomodulators for Curtailing COVID- 19: a Positive Approach. Journal of drug delivery and therapeutics. 2020; 10(3):286-294. DOI https://doi.org/10.22270/jddt.v10i3-s.4085
67. Islam SN, Begum P, Ahsan T, et al. Immunosuppressive and cytotoxic properties of Nigella sativa. Phytother Res. 2004; 18(5):395-398 DOI: https://doi.org/10.1002/ptr.1449.
68. Ciesielska-Figlon K, Wojciechowicz K, Wardowska A, et al. The Immunomodulatory Effect of Nigella sativa" Antioxidants. Natural and Synthetic Antioxidants. 2023; 12(7):1-13. https://doi.org/10.3390/antiox12071340.
69. Ciesielska-Figlon K, Daca A, Kokotkiewicz A, et al. The influence of Nigella sativa essential oil on proliferation, activation, and apoptosis of human T lymphocytes in vitro. Biomed Pharmacother. 2022; 153. 113349. DOI: 10.1016/j.biopha.2022.113349
70. A Zaoui, Cherrah N, Mahassini K, et al. Acute and chronic toxicity of Nigella sativa fixed oil, Phytomedicine, 2002; 9(1):69-74.https://doi.org/10.1078/0944-7113-00084.
71. Keshri G, Singh MM, Lakshmi V, et al. Post-coital contraceptive efficacy of the seeds of Nigella sativa in rats. Indian J Physiol Pharmacol. 1995; 39(1):59-62.
72. Mohideen S, Ilavarasan R, Sasikala E, et al. Hepato-protective Activity of Nigella sativa Linn. Indian journal of pharmaceutical sciences. 2003; 65(5):550-551.
73. Al Mofleh IA, Alhaider AA, Mossa, JS, et al. Gastroprotective effect of an aqueous suspension of black cumin Nigella sativa on necrotizing agents-induced gastric injury in experimental animals. Saudi J Gastroenterol. 2008; 14(3):128–134.
DOI: 10.4103/1319-3767.41731.
74. Umar S, Zargan J, Umar K, et al. Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats. Chem Biol Interact. 2012; 197(1):40-46. DOI: 10.1016/j.cbi.2012.03.003.
75. Kalus U, Pruss A, Bystron J, Effect of Nigella sativa (black seed) on subjective feeling in patients with allergic diseases. Phytother Res. 2003; 17(10):1209-1214. DOI: https://doi.org/10.1002/ptr.1356
76. Gul R, Tansuker HD, Cengiz AB, et al. Effects of nigella sativa oil on allergic rhinitis: an experimental animal study. Braz J Otorhinolaryngol. 2022; 88(5):148-S155. DOI: 10.1016/j.bjorl.2022.09.003
77. Naghsh N, Moridpour AH, Kavyani Z, et al. The effect of Nigella sativa (black seed) supplementation on body weight and body composition: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials. Journal of Functional Foods. 2023; 105:105565 https://doi.org/10.1016/j.jff.2023.105565.