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. 2022 Sep 13;11(18):2826. doi: 10.3390/foods11182826

A Narrative Review on Various Oil Extraction Methods, Encapsulation Processes, Fatty Acid Profiles, Oxidative Stability, and Medicinal Properties of Black Seed (Nigella sativa)

Muhammad Abdul Rahim 1, Aurbab Shoukat 2, Waseem Khalid 1, Afaf Ejaz 1, Nizwa Itrat 3, Iqra Majeed 3, Hyrije Koraqi 4, Muhammad Imran 1,*, Mahr Un Nisa 3, Anum Nazir 3, Wafa S Alansari 5, Areej A Eskandrani 6, Ghalia Shamlan 7, Ammar AL-Farga 5
Editors: Katarzyna Ratusz, Iwona Scibisz, Małgorzata Wroniak
PMCID: PMC9498113  PMID: 36140949

Abstract

The current review investigates the effects of black seed (Nigella sativa) on human health, which is also used to encapsulate and oxidative stable in different food products. In recent decades, many extraction methods, such as cold pressing, supercritical fluid extraction, Soxhlet extraction, hydro distillation (HD) method, microwave-assisted extraction (MAE), ultrasound-assisted extraction, steam distillation, and accelerated solvent extraction (ASE) have been used to extract the oils from black seeds under optimal conditions. Black seed oil contains essential fatty acids, in which the major fatty acids are linoleic, oleic, and palmitic acids. The oxidative stability of black seed oil is very low, due to various environmental conditions or factors (temperature and light) affecting the stability. The oxidative stability of black seed oil has been increased by using encapsulation methods, including nanoprecipitation, ultra-sonication, spray-drying, nanoprecipitation, electrohydrodynamic, atomization, freeze-drying, a electrospray technique, and coaxial electrospraying. Black seed, oil, microcapsules, and their components have been used in various food processing, pharmaceutical, nutraceutical, and cosmetics industries as functional ingredients for multiple purposes. Black seed and oil contain thymoquinone as a major component, which has anti-oxidant, -diabetic, -inflammatory, -cancer, -viral, and -microbial properties, due to its phenolic compounds. Many clinical and experimental studies have indicated that the black seed and their by-products can be used to reduce the risk of cardiovascular diseases, chronic cancer, diabetes, oxidative stress, polycystic ovary syndrome, metabolic disorders, hypertension, asthma, and skin disorders. In this review, we are focusing on black seed oil composition and increasing the stability using different encapsulation methods. It is used in various food products to increase the human nutrition and health properties.

Keywords: black seed (Nigella sativa), extraction methods, fatty acid composition, oxidative stability, encapsulation, food applications, health benefits

1. Introduction

Black seed (Nigella sativa) is an annual flowering plant in the Ranunculaceae family and Plantae kingdom. Black seeds are mostly found in western Asia, the Mediterranean North Sea area, and western and southern Europe. The black seed is also described in the Bible as the “healing black seed”, Hippocrates and Discroides termed it as Melanthion, and Pliny coined it Gith [1]. According to the world’s agricultural production, the production of oil seed is 40.29 million metric tons in Pakistan; in all the world, it is 607.3 million metric tons [2]. According to the Unani Tibb medical system, Nigella sativa. has proved very helpful in curing many health disorders. Nigella sativa has been used since ancient times in various civilizations of the world, and it is recommended as a “miracle cure” because it has the potential to cure several diseases and regulate the process of natural healing in the human body [3]. According to Indian medicinal culture, seeds can be consumed as a bitter, anthelmintic, astringent, jaundice, stimulant, intermittent fever, diuretic, paralysis, emmenagogue, piles, skin diseases, and dyspepsia [4,5]. They can be utilized in the form of an anti-cancerous, -diabetic, -bacterial, hepato-toxic, -parasitic, and -fungal, as well as a therapeutic agent. Black seeds in herbal medicines are consumed directly as an active ingredient or in the form of herbal tea. The black seed extract has the tendency to show anti-oxidant and -inflammatory properties. It has been used by patients to suppress coughs, disintegrate renal calculi, impede the carcinogenic process, treat abdominal pain, diarrhea, flatulence and polio, exert choleretic and uricosuric activities [4,6]. According to former literature, Nigella sativa seeds show various properties against different kinds of cancer, such as blood, [7] skin, [8] cervical, [9] colon, [10] hepatic, [11] prostate, [12] breast, and renal [13]. The extract, seeds, and oil of Nigella sativa have proved to manage oxidative stress, hypertension, and diabetes, as well as [14] ulcers, [15] epilepsies, [16] fatty liver, [17] asthma, [18] arthritis, [19] inflammatory disorders, [20] cancers, [21], and parasitic diseases [22,23], in humans [24].

Nigella sativa is consumed in folk and Unani medicines in Pakistan. By following the previous literature, Nigella sativa has great potential for disease curing and health improvement; more research work has been needed to convert the herbal medicinal culture to new medicine systems. The thymoquinone contains a carbonyl polymer called Nigellon. Oil of N. sativa seeds and its active ingredients reveal therapeutic functions such as antiviral, antimicrobial, lowering the blood sugar level, antitumor, anti-oxidation, muscle relaxation, and anti-inflammatory [25,26,27,28]. Formerly, different kinds of chemical compounds were isolated from various species of Nigella sativa [29]. Hence, Nigella sativa has 84 g fiber, 216 g protein, 45 g ash, 38 g moisture, 406 g fat, 249 g free nitrogen extract, 60 mg zinc, 105 mg iron, 527 mg phosphorus, 15.4 mg thiamin, 18 mg copper, 57 mg niacin, 0.16 mg folic acid, and 1860 mg calcium per kg [30]. Nigella sativa is recognized as an annual herbaceous plant, which is included in the family Ranunculaceae and largely cultivated in different regions of southern Europe, as well as a few areas of Asia [31], which includes Saudi Arabia, Pakistan, Syria, India, and Turkey [32]. The colors of its flowers are mainly white, pink, yellow, light blue, or lavender, and its flower makeup has 6–10 petals. The fruity portion of the plant is a bulky and balloon-like capsule, which carries many black seeds with a bitter and aromatic taste [4]. The farming time for Nigella sativa falls between November and April, and its germination period is completed two weeks after seed sowing. However, the fruits are usually obtained from plants from January to April [33]. Nigella sativa seed oil and their active ingredients have been used in many dishes for chilling and flavoring [34]. About 28–36% fixed oil is present in Nigella sativa seeds, and it consists of a diverse range of unsaturated fatty acids, such as linolenic, arachidonic, linoleic, and eicosadienoic acids. In contrast, saturated fatty acids are myristic, stearic, and palmitic acids [35]. The other components of seed oil are citronellyl acetate, cholesterol, carvone, campesterol, α-spinasterol, stigmasterol, p-cymene, β-sitosterol, palmitoleic, oleic, citronellol, nigellone, and limonene [36]. The fixed oil contains 12.5% of oleic, linoleic, and palmitic acids; the volatile oils contain carvone, trans-anethole, limonene, and p-cymene [37]. The oil also contains considerable amounts of carbohydrates, amino acids, fixed or volatile oils, and proteins [32]. However, the versatility in the pharmacological properties of seeds is mainly due to the presence of quinine constituents, the most abundant of which is thymoquinone. The volatile oils of black seeds have larger quantities of thymoquinone. Gali-Muhtasib et al. [38] explained that thymoquinone, flavonoids, alkaloids, and tannins are the active ingredients of black seeds, extracted with ethyl alcohol and cold water [39]. Nowadays, Nigella sativa oil is categorized as functional oil because it has a high content of omega-9 (oleic, 15–24%) and -6 (linoleic, 54–70%) fatty acids, as well as others found in minor amounts [40]. This crude oil has a protective effect, mostly on nerve cells [41] and the liver [42]. In addition to other biological functions, Nigella sativa crude oil a carries small amount of volatile oil and exhibits functional properties, due to thymoquinone. This crude oil is safe and largely utilized in dietary supplements because it has less toxic effects [43]. The key constituent of oil is thymoquinone, which performs its function as an anti-epileptic agent [44]. This extract also contains tannins, terpenes, alkaloids, glycosides, saponins, steroids, and flavonoids [45]. Biologically active compounds of Nigella sativa are not stable during different chemical reactions, and their prescribed amount was not appropriate for clinical research. The Nigella sativa seeds also have unsaturated fatty acid esters with nigellimin, terpene alcohols, saponin, and the alkaloid nigellidine [46,47]. According to Agbaria et al. [48], the unroasted seeds have less anti-proliferative activity than the pretreated heated seeds (50–150 °C, about 10 min) for the milling process. Initially, the oxidation process was low; it was enhanced during storage (about 55 days) and leveled off [49]. To overcome all of the above-mentioned issues, different encapsulation techniques have been used for black seed oil and their active components. It is the most successful method for protecting thymoquinone (Figure 1). Today’s black seed oil is microencapsulated with emulsification processes spray-drying and nanoprecipitation. This encapsulated black seed oil has high phytochemical content, which improves the nutritional status of food items. Nigella sativa oil is consumed as a functional ingredient in food systems. It can be utilized in the form of flavoring and seasoning agents during food product development [50,51]. The objective of this research is to provide a narrative review of black seeds and its active ingredients, with different oil extraction methods and a characterization of different encapsulation processes, fatty acid profiles, oxidative stability, and medicinal properties. Black seed contain a high content of bioactive compounds, in order to define its intrinsic pharmaceutical and nutraceutical actions and provide future research directions for identifying novel drugs. Although other authors have previously reviewed some aspects of chemical properties, the effects of various pretreatments on its stability, and quality analysis studies, our review provides a more comprehensive analysis of the related studies.

Figure 1.

Figure 1

Nigella sativa oil extraction and its chemical composition.

2. Extraction of Oil from Nigella sativa Seeds by Using Different Novel Techniques

2.1. Cold Pressing

Oil can be extracted from Nigella sativa seeds by using the different methods. According to the Kiralan et al. [52], the cold pressing method is suitable for extracting Nigella sativa oil from seeds. In this method, mechanical pressing was used for the pressing of seeds at a temperature of 25 °C. Furthermore, the separation of oil and crushed seed fiber has been performed by soaking the solution for one night at a 25 °C temperature. After that, filtered oil was obtained by using a glass funnel and Watman #4 filter paper (0.45 μm, Vivascience AG, Hannover, Germany).

2.2. Supercritical Fluid Extraction

Another innovative method for the extraction of Nigella sativa oil from seeds was used by Mohammed et al. [53]. The supercritical fluid extraction equipment (FeyeCon Development B.V. Weesp, Netherlands) was used for Nigella sativa seed oil extraction, by using a stainless steel grinder (Waring Commercial, Torrington, CT, USA) for 3–4 min; the crushed dried seeds were obtained, placed the material in a 50-L container of extractor, and sealed tightly. The system used an automatic back pressure regulator for maintaining the temperature at 40 °C for 1 h; the pressure was 600 bar, and the flow rate of injected liquid carbon dioxide (CO2) was 150 L/h.

Rao et al. [54] also chose the supercritical fluid extraction method for Nigella sativa seed oil extraction. In its instrumentation, it contained a syringe pump with 260 mL capacity, controller system (ISCO 260D), and ISCO series 2000 SCF extraction system (SFX 220), consisting of a dual chamber extraction module with two 10 mL stainless steel vessels. Hence, about 5 g of ground black seeds were added in a stainless steel cell (10 mL). Then, the standard quantity of supercritical carbon dioxide (SC CO2) (50–400 mL) was flushed into the cell at a 1 mL/min flow rate. The final concentration of the extract was collected in the cold trap. After optimization of supercritical fluid extraction conditions, the lower yield of 0.84% (508 °C, 400 bar, and 100 mL) and higher yield of 31.7% (508 °C, 100 bar, and 200 mL) were obtained at optimum levels.

2.3. Soxhlet Extraction

Dinagaran et al. [55] used the soxhlet apparatus for Nigella sativa oil extraction from black seeds. For this purpose, Nigella sativa seeds were collected from different regions of India, including Tamil Nadu, Triplicane, and Chennai. During the sieving process, the small and contaminated seeds were removed at room temperature. In this process, the seeds were first ground using a tabletop mixture, hexane was used for extraction of seed oil for approximately 2 h in a soxhlet apparatus, and the extracted oil was stored at room temperature in a selected amber glass bottle until use. Nigella sativa seed has 28–35% fixed oil, which mainly consists of unsaturated fats. Through gas chromatography–mass spectrometry (GC-MS) analysis, 32 different compounds were found in black seeds.

2.4. Hydro Distillation (HD) Method

Kokoska et al. [56] selected the hydro distillation (HD) method for the extraction of oil from Nigella sativa seeds. In the first step, the seeds were ground at 25 °C. Then, they weighed the 70 g sample to be used for further analysis. The average yields were achieved and figured on a dry weight basis. For attaining essential oil through the HD method, they used a water holding flask for placing the material. It is called a Clevenger-type apparatus because the flask is directly connected to the condenser. After 2 h of continuous processing, a yield of 0.29 wt/wt of pale-yellow oil was obtained.

Burits and Bucar [57] also chose the same technique for oil isolation, and an Austrian pharmacopoeia (Clevenger apparatus) was used as standard apparatus in the whole process. The results were not satisfactory because the oil extracted had lower quantities of essential oil, with only 3% thymoquinone content, while Soxhlet extraction yielded 48% thymoquinone content.

2.5. Microwave-Assisted Extraction (MAE)

Abedi et al. [58] performed the oil extraction through a domestic microwave oven (Daewoo Electronics KOC-154KWR Microwave Oven) with a frequency of 2450 MHz. Initially, they took 50 g of ground seeds and selected a 500 mL round-bottomed flask for the soaking of seeds in 50 mL of water for about half an hour. After that, the Clevenger apparatus was fixed with a flask and utilized 450 W of power for heating (30 min). However, the essential oil was leached out in the n-hexane solvent. Only 0.33% essential oil yield was achieved by using MAE extraction conditions (power 450 W, moisture content 50%, and time 30 min).

2.6. Ultrasound-Assisted Extraction

Moghimi et al. [59] used an ultrasound-assisted extraction method for oil extraction. For one treatment, a sample of 500 g was transferred to the 1.5-l container that was placed in the ultrasonic bath. Several optimization conditions were selected, including the time (30, 45, and 60 min) and ultrasound pretreatment power (30, 60, and 90 W) at a fixed frequency of 25 kHz. After completing this process, the oil was isolated by using a screw press at 33 rpm speed. The maximum results of 39.93% extraction efficiency were achieved at power of 90 W and time of 60 min, while the minimum results of 27.29% extraction efficiency were achieved at power of 30 W and time of 30 min.

2.7. Steam Distillation

For the prevention of the side effects of degradation, steam distillation was performed at a low temperature. In 100 mL of distilled water, 10 g of seeds were added and mixed. This mixture was quantitatively transferred into the separatory funnel. This process of extraction was performed three times; a total of 10 mL of diethyl ether was added at every step, and the funnel was shaken vigorously. Sodium sulfate was used to dry the organic layer, and 0.4% was the obtained yield after evaporation in the water bath [60]. The steam distillation process was used by Kokoska et al. [56]. A glass column-containing material was interpolated between the condenser and flask. The yield of oil that was extracted by steam distillation was 0.39%, and the color of the oil was pale yellow.

2.8. Accelerated Solvent Extraction (ASE)

A 1 g sample of black seeds in powdered form was taken in a stainless steel cell with a 34 mL capacity. The conditions were set: 100 atm pressure, 10 min static time, 20% rinse volume, 2 extraction cycles, 30 s purge time, and 26 mL of solvent volume. P1-P9 black seed samples from Pakistan, Indian, and Saudi Arabian were treated with n-hexane as P1-P3, methanol (MeOH), and dichloromethane (DCM) at 40 °C, P4-P6 with MeOH, DCM, and n-hexane at 50 °C; the same procedure was performed for P7-P9 at 70 °C. The results reveal that the solvent with high yield, following n-hexane, was MeOH, whereby the yield and recovery observed was 2.5 g (12.5%) for Saudi Arabia, 2.2 g (11%) for Pakistan, and 2.04 g (10.2%) for Indian black seed sample [61] (Table 1).

Table 1.

Different extraction methods of Nigella sativa seeds oil.

Extraction Method Solvent Used Advantage Disadvantage Yield/Efficiency Source
Cold pressing Hexane Involves no heat or chemical treatments during oil extraction Provides low yield 27% [62]
Supercritical fluid extraction SC CO2 Rich in antioxidants High cost 31.7% [54]
Soxhlet extraction Methanol Low in cost Residues of solvent has been left behind in the extracted oil 29.9% [55]
Hydro distillation (HD) method Water Very simple method and instrument, shorter extraction time, free from organic components, less labor consumption, good in quality, lower cost with good efficiency High energy is required for extraction 0.29% [56]
Microwave-assisted extraction (MAE) n-hexane Free from organic solvent, less time with maximum yield Additional filtration or centrifugation required to remove the solid residue 0.33% [58]
Ultrasound-assisted extraction Hexane Less energy and solvent consumption, reduced time of extraction 39.93 [59]
Steam distillation Sodium sulphate Performed at a low temperature to prevent from degradation More time consuming, due to the low pressure of rising steam 0.40% [60]
Accelerated solvent extraction MeOH, DCM, and n-hexane A latest and efficient method for extraction 2.5 g, 2.2 g, and 2.04 g [61]

3. Fatty Acid Profile of Extracted Oil

Nigella sativa seed oil, extracted from black seeds, contain a considerable amount of polyunsaturated fatty acids (PUFAs), with a minor amount of long-chain polyunsaturated fatty acids. The fatty acids composition of black seed oil contains the lauric (0.6%), myristic (0.16%), palmitic (11.4%), margaric (0.07%), stearic (3.2%), palmitoleic (1.15%), margaroleic (0.04%), oleic (8.1%), eicosenoic (0.4%), linoleic (55.6%), linolenic (2.45%), behenic (0.87%), erucic (1.0%), lignoceric (0.02%), eicosapentaenoic (5.98%), and docosahexaenoic (2.97%) acids. The results of another research work showed that black seed oil is higher in components such as linoleic (427.8 g/kg) and oleic (294.3 g/kg) acids, while it also contains other constituents, such as that of the lauric, myristic, myristoleic, pentadecanoic, palmitic, palmitoleic, heptadecanoic, heptadecenoic, stearic, elaidic, oleic, linoleic, linoleic, linolenic, arachidic, gadoleic, eicosadienoic, behanic, erucic, and lignoceric acids. Moreover, the fatty acid profile of black seed oil showed the concentration of linoleic acid to be the highest (58.9%), with prominent oleic (28.1%), palmitic (12.5%), and stearic (3.1%) acids, respectively [63,64,65]. In another recent research work, carried out by Farhan et al. [66], the fatty acid composition of black seed oil was made up of the myristic (0.24%), palmitic (11.10%), palmitoleic (0.23%), heptadecanoic (0.56%), stearic (2.60%), oleic (24.6%), linoleic (58.8%), arachidic (0.22%), linolenic (0.4%), eicosenoic (0.18%), eicosadienoic (0.22%), eicosatrienoic (0.74%), and behenic (0.11%) acids. However, black seed oil contains a high percentage of triacylglycerides, especially acyl groups of oleate and linoleate, which are considered essential and omega-rich sources. Black seed oil contains omega-3 (Ω-3), -6 (Ω-6), and -9 (Ω-9) fatty acids, as well as bioactive compounds, which are used to reduce the risk of cardiovascular disease, inflammation, hypertension, oxidative stress, hormonal disorders, chronic cancer, diabetes, neurodegenerative diseases, metabolic, and skin disorders, while also improving immunity and blood vessel circulation [67,68] (Table 2).

Table 2.

Fatty acids profile of Nigella sativa seed oil.

Carbon Chain Chemical Name Procurement Oil Extraction Method Percentage (%) Chemical Formula Chemical Structure References
Saturated fatty acids
C12:0 Lauric acid Iran Hydrodistillation 0.6 C12H24O2 graphic file with name foods-11-02826-i001.jpg [37]
C14:0 Myristic acid Middle East Soxhlet extraction 0.16 CH3(CH2)12COOH graphic file with name foods-11-02826-i002.jpg [69]
C16:0 Palmitic acid Izmir Steam distillation 11.4 C16H32O2 graphic file with name foods-11-02826-i003.jpg [70]
C17:0 Margaric acid Konya, Turkey Microwave-assisted extraction 0.07 C17H34O2 graphic file with name foods-11-02826-i004.jpg [52]
C18:0 Stearic acid Moroco Solvent extraction 3.2 C18H36O2 graphic file with name foods-11-02826-i005.jpg [62]
Monounsaturated fatty acids
C16:1 Palmitoleic acid Tunisia Cold solvent method 1.15 C16H30O2 graphic file with name foods-11-02826-i006.jpg [71]
C17:1 Margaroleic acid Turkey Soxhlet extraction 0.04 C18H30O2 graphic file with name foods-11-02826-i007.jpg [52]
C18:1 Oleic acid India Solvent extraction 8.1 C18H34O2 graphic file with name foods-11-02826-i008.jpg [72]
C20:1 Eicosenoic acid Germany Method ISO 659:1998 0.4 C20H38O2 graphic file with name foods-11-02826-i009.jpg [73]
Polyunsaturated fatty acids (PUFAs)
C18:2 Linoleic acid India Soxhlet extraction 55.6 C18H32O2 graphic file with name foods-11-02826-i010.jpg [55]
C18:3 Linolenic acid Isfahan, Iran Modified Bligh–Dyer method 2.45 C18H30O2 graphic file with name foods-11-02826-i011.jpg [74]
Long chain polyunsaturated fatty acids
C20:3 Eicosatrienoic acid Saudi Arabia Soxhlet extraction method 0.74 C20H34O2 graphic file with name foods-11-02826-i012.jpg [66]
C20:5 Eicosapentaenoic acid Iraq Soxhlet extraction method 5.98 C20H30O2 graphic file with name foods-11-02826-i013.jpg [64]
C22:6 Docosahexaenoic acid 2.97 C22H32O2 graphic file with name foods-11-02826-i014.jpg

4. Oxidative Stability of Extracted Oil

The initial concentration of black seed oil primary oxidation products was very low, but enhanced, during the storage time of 55 days and then flattened. During this storage period of 55 days, nanoparticles of less encapsulated efficiency increased their peroxide values. The peroxide value of these nanoparticles was lower than the initial value of peroxide [49]. Due to the increase in temperature, the peroxide values also increased. The peroxide value of unencapsulated black seed oil was more than nanoparticles [75]. During storage, the secondary oxidation product formation was determined by the p-anisidine value [76]. In the unencapsulated black seed oil, the p-anisidine value was more than in nanoparticles, which showed that the effect of encapsulation is protective [77]. The totox values at the same temperature and storage time were observed. At 25 and 60 °C, the highest totox were determined in unencapsulated samples at the end of storage time. The increase in the totox value of the encapsulated samples was less because of the extra layer provided by the coaxial process [78]. The stability of black seed oil is improved using the various micro- and nano-encapsulation techniques at optimum conditions. It also provides many advantages, including improved thermal and chemical stability, preservation of the taste and flavor, controlled and targeted release, and the improved bioavailability of natural pigments [79].

Technologies to Extend the Oxidative Stability of Black Seeds Oil

Different technologies have been used to improve the oxidative stability of black seed oil and its components, as presented in Table 3. The high concentration of thymoquinone is present in black seed oil; as reported by Ravindran et al. [80], this compound is sensitive to oxygen, light, heat, moisture, and food processing or storage conditions. The thymoquinone in black seed oil is protected by encapsulation. The microencapsulation is achieved by the emulsification process, [50] spray-drying [51], and nanoprecipitation [81]. These processes take more time and involve hot gas streams; therefore, they are not appropriate for bioactive substances that are heat sensitive [82]. For sensitive compounds, alternative techniques are required to overcome the drawbacks of the conventional method of encapsulation.

Table 3.

Technologies use to enhance the oxidative stability of black seed oil and their components.

Source/Component Method Capsulation Efficiency/Yield Peroxide Value Size Detection Particle Size Conclusion References
Thymoquinone Nanoprecipitation Nanoparticles 97.5% - Transmission electron Microscopy 150 and 200 nm Thymoquinone nanoparticles showed that the higher bioavailability; therefore, it can be used as anti-proliferative, anti-inflammatory, and chemo sensitizing agents against many disorders in humans and animals. [80]
Black seed oil Ultra-sonication and spray-drying Micro- and nano-encapsulation - 100 μg Fe3+ Electron microscope Microencapsulation = 250 nm to 400 nm; nanoencapsulation = 50 to 188 nm The oxidative stability of encapsulated materials was improved during storage, and its stability was close to fresh oil. [50]
Oleoresin Spray-drying Encapsulation 84.2 to 96.2% - Static light scattering instrument 3.08 to 11.84 μm Microcapsules can be used as a functional ingredient in various processed food and meat products, as well as in nutraceutical and other pharmaceutical applications with maximum stability. [51]
Nigella sativa seeds oil Nanoprecipitation Nanoparticles 70% to 84%. - Malvern particle size analyzer 230 to 260 nm The stability of nanoparticles was significantly improved after 30 days of storage. These nanoparticles can be used to improve skin penetration and reduce systemic concentration. [81]
Black seed oil Electrohydrodynamic atomization Encapsulation 67.201% to 104.50% - Olympus light microscope Oil emulsion = 282.93 to 463.23 nm The results revealed that the emulsion with lecithin exhibited the higher emulsion stability (3% and 1%). [125]
Black seed oil Freeze-drying Encapsulation 63% to 87% - Inverse phase microscopy 173 to 382 nm The stability of encapsulation showed that the liposomal preparation was stable at ambient conditions for one month. [96]
Black seed oil Electrospray technique Microencapsulation 100% - Digital microscope Less than 3 mm This study indicated the palatability was significantly improved in encapsulation, without reducing thymoquinone stability. [126]
Black seed oil Coaxial electrospraying Encapsulation 65.3% to 97.2% 19.50 to 30.57 meq O2/kg Field emission scanning electron microscope 116 to 257 nm Nanoencapsulation of black seed oil significantly improved the oxidative stability, due to form the coaxial structures. [127]
Black cumin seed oil Freeze-drying Encapsulation Plasmolyzed loaded yeast encapsule = 59.97%; non-plasmolyzed loaded yeast encapsule—39.18% Scanning electron microscopy - The stability of encapsulated black cumin seed oil with yeast cell of S. cerevisiae was successfully increased in suitable condition, compared to black seed cumin oil and nonplasmolysed yeast cell. [128]

The recently developed process for encapsulation technology is electrospraying. It is an alternative to conventional processes. This process is cost-effective and simple to produce a variety of nanoparticles. There is no need for heat during drying, and the formation of smaller encapsulates of 1–5 m is gaining importance in temperature-sensitive bioactive encapsulation [83]. This process includes a polymer solution; its surface is charged by an electrostatic field of high voltage and produces ultrathin droplets at room temperature after evaporation of solvent, resulting in the formation of dried capsules of micro and nano sizes [84].

An alternative procedure can be used for the black seed oil encapsulation with zein. Zein is a prolamin protein that is water insoluble and obtained from maize. This protein is hydrophobic in nature and used in coating materials for food. It is reported as a favorable and protective matrix used in the electrospraying process for bioactive compound encapsulation [85]. The atomization of solution polymer is involved in this process by a pneumatic injector, and a high electric field is used for nebulization. In this procedure, the evaporation of the solvent, by air at room temperature in a drying chamber, results in free-flowing powder containing encapsulated material being collected [86]. The efficiency of the electrospraying process is increased by EAPG and used in the industrial production of omega-3 capsules that are electro sprayed and used for food application [87].

For the ease and protection of handling, it involves the incorporation of functional or sensitive core substances, which are called encapsulates in the wall material [51]. In this process, thin coatings are used on dispersions, small liquid droplets, and solid particles [88]. The particles range in size from 1 to 1000 μm and have a core that is coated with synthetic or natural shells called microcapsules [89,90]. These microcapsules are used for the protection of oils from environmental factors [91]. This microencapsulation increases the shelf life of black seeds. The microencapsulation also helps in the regulation of the release rate of the oil, in order to sustain the absorption and maintain an appropriate concentration for the production of the desired effects [92]. The encapsulation of oils can be achieved via various methods, but electrohydrodynamic atomization (EHDA) is one of the most important for the production of nano- and micro-sized structures [93,94]. Various factors, such as the nozzle size, applied voltage, flow rate, and distance of the collection of the polymeric solution that is required to produce the desired size of particles or morphology, must be taken into account [95]. In the microencapsulation process, an electrospray technique is also used for the fabrication of a wide range of particle sizes [96]. To overcome the viscosity and surface tension of the polymeric solution, which leads to the distortion of particles at the needle tip, electrostatic forces are applied [97]. A jet of high charge density is produced, and then an array of charged beads of sizes ranging from millimeters to micrometers is produced by the shattering of the jet [98]. These droplets drop into a solution for cross-linking. The electrospraying process has been applied for the preparation of particles that are synthesized from synthetic and natural polymers [99]. The economically feasible and most common process for the encapsulation of powdered ingredients is spray-drying [100,101]. Different investigations into microencapsulation by spray-drying have been performed to check its protective effects against oxidation [102,103,104].

The anti-oxidant and -bacterial activities of essential oils can be improved by the emulsification process [105]. An emulsion can be defined as the dispersion of an immiscible liquid into another liquid, and this dispersion is stable [106]. It is difficult to protect encapsulated material from leaking and changing in its composition when small molecules are allowed to penetrate through the wall material during a specific time period [107]. To overcome this problem, a pre-encapsulation process and solid wall material are recommended [108,109,110,111]. Emulsification can be achieved before encapsulation [112,113]. This emulsion-based system has developed from the encapsulation process of dispersion of lipophilic ingredients in aqueous media. Various processes have been used for emulsion preparation, such as high-speed mixers, colloid mills, ultrasonic homogenization, and high-pressure homogenizers [114]. In the encapsulation process, the efficiency and stability of average-sized particles is difficult to maintain because particles of larger size have better protective effects, as compared to smaller ones; however, in the food matrix, they present low dispersion [110].

Encapsulation is commonly used to achieve food ingredients or any other components with a diameter of 1–1000 microns. Furthermore, when such terms are fulfilled, this methodology can allow for the sustained release of the encapsulated core [115]. Fatty acids, as well as artificial ingredients and coloring agents, have all been encapsulated using a spray dryer [116]. Encapsulation is also extensively used in various food industries to integrate oil aromas in a spray-dried form because it is cost-effective, versatile, can be used in a continuous mode, and yields better particles [117]. The most widely accepted encapsulation technology, used throughout the food market to encapsulate omega-3 fatty acids (PUFAs), is spray-drying [118]. Despite the short holding time of encompass in the drying medium (up to 60–80 °C), the oxidation of omega 3 PUFA is caused by temperature increment of encapsulate (up to 60–80 °C) during the spray-drying application’s falling-rate time frame [119]. Freeze-drying, but at the other hand, which also works under room temperature (e.g., vacuum and low temperature), has a lower bandwidth, and is expensive. Furthermore, the magnitude of encapsulates produced by the spray- and freeze-drying mechanisms is quite huge (10–100 m), which may have an adverse impact on the final enhanced product’s organoleptic characteristics [120]. Spray-drying is accomplished by converting a slurry emulsification from a fluid to a powder in a running condition by solubilizing the core materials in water to produce an emulsification in fluid state and feeding this emulsion into the hot form of media (100–300 °C) to evaporate water. The dried item can be obtained as powder or flocculated particles [121]. Spray-drying encapsulation has four different steps: (i) creating a stable emulsion; (ii) homogenizing the dispersion; (iii) atomizing the emulsion; and (iv) dehydrating the atomized particles. To achieve maximum concentration of the polymeric chains and inhibit any variability induced by temperature variations, the very first step is usually carried out by solubilizing the wall materials in filtered water, as well as emulsification, or dissipating using a stirring rod 24 h at 25 °C [122]. Based on the emulsification properties of the wall materials, core materials are blended with an aqueous medium of the internal walls; then, the emulsification agent can be added before entering the second phase. The created emulsion, which contains the wall, as well as core components, should be stable until the drying phase [123]. Spray-drying is the most cost-effective technique of encapsulation, when compared to other encapsulation methodologies. The encapsulation of oils incorporates a range of variables, such as inlet and outlet temperatures, total dissolved solids, and the form of internal walls used, all of which have significant effects on the resulting product’s quality [124].

5. Functionality in Food Applications

Natural foods that are high in nutrients and may have biological activities are in high demand among modern consumers (Table 4). This needs to motivate food makers and studies to develop novel food formulations that are supplemented with various substances [76]. Several earlier researches suggested enhancing the nutritional value of food products by adding oils high in phytochemicals. Nigella sativa oil has been proposed as a useful component in food [129]. Nigella sativa (Klonji) is a valued seasoning, with a particular aroma and flavor, that has been used in pickles, baked goods, confectionary, sauces, salads, and savory foods [130]. The seeds have been discovered to be utilized as a seasoning and flavoring agent in Indian and Middle Eastern cooking [131]. Nigella sativa seeds are used as a spice in a variety of cuisines [132]. To make a bitter qizha paste, the seeds are crushed [133]. Curries, veggies, and pulses all benefit from the dry-roasted seeds. They can be used in recipes with pod fruit, vegetables, salads, and chicken as a spice. Black seeds are used as part of the spice mixture in several cultures [134]. Black seed is also used in tresses cheese, a Middle Eastern braided string cheese known as majdouleh or majdouli. Black seed (Klonji) is a plant that is used as a food preservative, as well as a medicinal powder [25]. The biological actions of black seed oil are attributed to the presence of phytochemical molecules, known as thymoquinone, according to Hassanien et al. [135].

Table 4.

Food applications of black seed and their oil.

Procurement Type Preparation Method Product Name Quantity and Ratios Analysis Results References
Malaysia Nigella sativa oil Supercritical fluid extraction Ice cream 3%, 5%, 10%
5%, 10%, and 15%
Physiochemical stability Nigella sativa oil was significantly improved the stability of ice cream under optimize storage conditions. [138]
Iran Oil microcapsules Goff and Hartel’s method Ice cream 3 and 5% Antioxidants and phenolic content The results indicated that, in fortified ice cream, the resistance of melting, minerals, and activity of antioxidant significantly improved. [145]
Mansoura Black seed oil and powder Dried hot-air oven Ground mutton Black seed oil (1%, 2%, and 3%): powder (2%, 4%, and 6%) Antibacterial and antioxidant effect The results obtained by using 3% black seed oil and 4% powder in meat showed a decrease in the bacterial contamination, due to their anti-microbial properties. [146]
Poland Nigella sativa oil Convection–steam oven Pork patties 1.88% and 3.76% Sensory evaluation and antioxidant Nigella sativa oil significantly improved the antioxidant activity of fortified patties. [147]
India Black seed oil Ultrasound Skim milk 7% Physiochemical stability and size of emulsion Stable emulsions of 7% black seed oil and milk were produced at lower time. [148]
Polska Black seeds Freeze dried Chicken meat 15 g Antioxidant, phenolic contents, lipid oxidative stability, and microbial and sensory properties The addition of prepared extract was significantly decreased the oxidation, while the stability of chicken meat was significantly improved during stored at 4 °C, due to good antimicrobial properties of black seed. [144]
Turkey Black cumin oil - Mayonnaise 5, 10, and 20% Color, sensory, phenolic compounds, and oxidation Mayonnaise formulated with black cumin oil was showed that the reduction in oxidation rate and improve the shelf life and flavor, as compared to other treatments. [142]
Belgium Black cumin seed oil - Bread 1 and 3 mL/100 g Dough characteristics and bread analysis Bread prepared with black cumin oil has been revealed to have good antifungal activity. [149]
India Black cumin seeds - Cookies 2%, 4%, 6%, and 8% Chemical composition and sensory analysis The results indicated that the good quality of product was prepared at 4% and rich in nutritional properties, as compared to other treatments. [150]
Pakistan Black cumin seed oil Solvent extraction method Cookies 1, 2, 3, 4, and 5% Physicochemical, phenolic contents, peroxide value, and sensory analysis Black cumin seed oil had a positive impact on the physicochemical, peroxide value, and sensory analysis of cookies, due to the good nutritional properties. [151]
Egypt Black cumin seed oil Cold pressed Soft cheese 0.1% and 0.2% Microbial, physicochemical, sensory analysis Black cumin seed oil was improved the nutritional profile of cheese and antimicrobial activity against pathogens. [135]
Erzurum Black cumin - Meat balls 0.50 and 1% Physicochemical and antioxidant properties The concentration of heterocyclic aromatic amines in fortified meatballs was significantly reduced, while the antioxidant properties and phenolic compounds was increased, as compared to control. [152]
Turkey Black cumin honey - Yogurt 0, 2.5%, 5%, 10%, and 15% Phytochemical and antioxidants analysis Results showed that, generally, the addition of black cumin honey in yogurt resulted in a significant increase of total phenolic contents and antioxidants activities. [153]

Nigella sativa oil was utilized to fortify the ice-cream product, since oil-in-water nanoemulsion may readily be added to dairy products to boost their nutritional content. Because of their functional qualities in food processing, nano emulsions have been incorporated to a variety of food systems [136,137]. Nanoemulsion was used to incorporate Nigella sativa oil into an ice cream product. The NSO nanoemulsion improved the physical qualities of ice cream, as well as customer acceptance. Sensory evaluation of the various samples found that the ice cream sample with 5% nanoemulsion obtained the most acceptance from the panelists. The results showed that NSO nanoemulsion can be used to fortify ice cream [138]. As a result, it might be used as an innovative component in ice cream, with a wide range of black seed oil health benefits. However, because black seed oil has a bitter or strong peppery flavor in the mouth and may affect the taste of ice cream food products, it was recommended that the amount of black seed oil nano emulsion not be raised by 10% [71].

Mayonnaise is one of the world’s oldest and most extensively used sauces. Oil (70–80 percent), egg yolk, vinegar, and seasonings make up traditional mayonnaise. Mayonnaise is particularly sensitive to spoiling and auto-oxidation, due to its high oil content [139]. Consumers are increasingly interested in natural foods and preservatives, in order to live healthier lives. As a result, the food industry has been on the lookout for new and interesting spice flavors for ethnic and cross-cultural cuisines [140]. Because of their antioxidant characteristics [78] and health advantages, black seeds (Nigella sativa) and their crude or essential oils are widely employed in functional foods, nutraceuticals, and pharmaceutical products [135,141]. Mayonnaises supplemented with black seeds had superior oxidative stability, compared to mayonnaise made with SFO. The phenolic chemicals in black seeds, particularly thymoquinone, may play a role in oxidative stability. Using it in mayonnaise recipes as a natural antioxidant source could help reduce oxidation, hence improving shelf life and flavor [142].

Chicken meat is high in easily digestible proteins, including omega enrich, lipids with a high PUFAs content, vitamins, and minerals. The increased degree of PUFAs in chicken flesh increases oxidative processes, thus resulting in a quicker loss of meat quality, when compared to other varieties of meat. Physicochemical qualities, biochemical and physiological profiles, and food hygiene all suffer from lipid oxidation. Furthermore, undesirable bacteria, initiated from animals, slaughterhouses, processing, and high temperatures, can contaminate chicken meat. Herbs and spices have been used for curing meat to give it a distinct flavor and keep it from spoiling during storage [143]. Plants and their extracts have a good effect on meat quality, which has been attributed to their high antioxidant and antibacterial activity. There has not been much research into the effectiveness of black seed extract in the muscle food system. The antioxidant capabilities of black seed have been used to protect meat products from oxidation. Black seed extract has the potential to significantly extend the shelf life of raw ground chicken flesh. It also ensures that the microbiological quality of the chicken flesh is maintained. The extract of black seeds improved the oxidative stability and safety of meat, changed the color of the samples dramatically, and stabilized the pH. The antioxidant capacity of black seed extracts was high in the lipid and protein fractions, whereas the ABTS•+ radical scavenging activity of black seed extracts was much lower [144].

6. Health Benefits of Nigella sativa

Nigella sativa are considered seeds of blessing in Arabic folk medicines. N. sativa are widely used in treatment of communicable and non-communicable diseases. The common issues of health, such as the common cold, chronic migraine headaches, and mild abdominal pain can be cured with the N. sativa tea. Black cumin was also used by ancient Chinese for improved liver function. Medicinal plants, such as black cumin, are used for curing of respiratory track ailments, including asthma, bronchitis, and rheumatism. Across middle Asia and southern countries, the digestive system is the most important system of the body for overall health and immunity of the body. Black cumin can help with the overall improvement of digestive functions, with an astonishing potential to treat the malfunction of digestive system organs. This seed of blessing can improve anorexia among patients and enhance the digestibility of food. The extract of black cumin can treat diarrhea, indigestion, and vomiting. Moreover, N. sativa has the potential to treat menstrual pain, and it is helpful for amenorrhea management. Roasted black cumin is recommended for vomiting as a quick remedy. The anti-viral power of these seeds can enhance immunity and is used for seasonal viral ailments. The therapeutic intervention also includes anti-bacterial, -inflammatory, -septic, and -fungal conditions. The health benefits of black cumin oil for skin conditions includes curing eczema, alopecia, freckles, and leprosy [1,154,155].

The pharmacological and biological activities include a wide range of applications. The powerful anti-inflammatory extract of N. sativa can inhibit the pro-inflammatory cytokines, interleukin 1 beta, and interleukin 6 (IL-6). The consumption of 500 µL of N. sativa for a month can improve the condition of chest congestion and treat sneezing. This extract can ameliorate allergic arthritis and hypertrophy of sinusitis patients. The bio active compound thymoquinone (TQ) possess hepatoprotective and nephroprotective power. The thymoquinone in black cumin has a strong antioxidant potential and treats lipid peroxidation. This is the most important bioactive compounds found in black cumin for the protection of heart diseases. The antiproliferative and proapoptotic activities of black cumin is astonishing in the prevention of abnormal lipid levels. The cardioprotective effects of N. sativa protects myoblast cells; it also protects against toxicity [156,157].

The properties result in the cell arrest and apoptosis of mutant cells. The anti-carcinogenic activity modulates the mutant cell into self-suicide and prevents cancer cell metastasis. A different animal trial described the positive outcomes of black cumin seed oil in the protection from cardiotoxicity. Black cumin seed oil can treat cardiac tissue damage and lower oxidative stress. Moreover, human trials at the dosage of 500 mg explained the neuroprotective potential. The better concentration, with improved memory and enhanced cognitive abilities, are the marvelous positive outcomes of N. sativa Oil consumption [158]. In addition to all these therapeutic applications of black cumin, a rat study explained the mechanism regarding Parkinson’s treatment by reducing oxidative stress, along with an increased amount of superoxide dismutase in the midbrain. The immunity enhancing properties are not only confined to neuroprotection, but also ameliorate the joint inflammation and lower the level of C reactive proteins. Both humoral and cellular immunity can be modulated by the usage of the blessed seeds from the prevention to treatment of simple to complex conditions (Figure 2) [159].

Figure 2.

Figure 2

Nigella sativa health benefits.

6.1. Medicinal Properties of Nigella sativa

Besides its medical properties, Nigella sativa also possess numerous pharmacological and biological activities and have been used as nutraceutical purposes and pharmaceutical alternatives, similar to dietary supplements that claim to have physiological benefits that could protect against chronic diseases. The medicinal properties of Nigella sativa are shown in Figure 3 [160].

Figure 3.

Figure 3

Medicinal properties of Nigella sativa.

6.2. Antiviral Activity of Nigella sativa against Other Medically Important Viruses

Viruses require a living cell for multiplication and cause disease in those cells and individuals. Black cumin seeds can help in the treatment of viral infections. The notorious virus in the human population for adverse outcomes includes hepatitis C virus (HCV) and HIV [161,162].

6.2.1. Antiviral Activity of Nigella sativa against Human Immunodeficiency Virus

A pilot study was conducted by Maideen and Mohamed [163] regarding the N. sativa seeds for patients of AIDS. AIDS is a life-threatening disease that starts from asymptomatic stage of disease and progresses to symptomatic after years. HIV is the main cause of this condition, which not only a treat to life in itself, but also includes opportunistic infections to the person. This virus directly attacks the immune cells and deteriorates the immunity of the patient. A concoction based on N. sativa and honey was given to 51 patients in that study for 5 months. The results showed that the concoction, along with anti-retroviral therapy, was found to be effective in the reduction of the viral load. It enhances the overall immunity of the patients and increases the immune cells. The concoction increased the differentiation of CD4 cells among patients. These results promote the blessing seeds importance for HIV treatment. Globally hepatitis c is a viral disease and affects more than 179 million people. Hepatitis, due to any virus, results in liver cancer and causes miserable life conditions [164]. A self-controlled pilot study conducted in Egypt explained the potential of hepatic cell protection. N. sativa seed oil capsules of 450 mg potency were given to 30 patients with hepatitis. The oil of blessing seeds significantly reduced the viral load from the baseline values. Additionally, the controlled blood sugar level, with increased overall antioxidant capacity, were seen among patients. Improvements were seen in the liver function tests, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactose dehydrogenase (LDH), and serum alpha-fetoprotein (AFP). The overall health of patients was improved via a decrease in the viral load, replication, and oxidative stress. Hepatitis B is more dangerous and life threatening, according to WHO. Millions of people suffer from this virus and end up with hepatocellular carcinoma. N. sativa being anti-viral, hepatoprotective, immune-protective, and anti-inflammatory is the best solution, with multiple health benefits [165].

6.2.2. Antiviral Activity of Nigella sativa against SARS-CoV-2

N. sativa is famous for its medicinal worth from centuries against pathogens. The application as anti-SARS-CoV-2 agents enlightened its worth during pandemic of COVID-19. N. sativa tea with honey can ease the symptom of COVID-19 and improve immunity [166,167,168].

6.3. Role of Nigella sativa against Asthma

Asthma is a chronic inflammatory disorder of the respiratory tract. The inflammatory cells involved in this condition are eosinophils, t cells, macrophages, neutrophils, epithelial, and mast cells. Different environmental factors that are involved in the worsening of asthma include seasonal allergies and dust. Inflammation may be present in both allergic and non-allergic asthma. Mast cells cause inflammation in the air ways among patients of asthma. Black cumin seeds inhibit inflammation. Thymoquinone can inhibit leukotriene formation in human blood, through the inhibition of various enzyme activity. Thymoquinone functions as an anti-oxidant, with anti-inflammatory and -allergic potency to treat airway hypersensitivity-related diseases, including asthma. Bronchodilation and anti-allergic actions of extract of blessing seeds was also proven in preclinical studies [18,169].

6.4. Antioxidant Activity and Bioactive Compounds of Nigella sativa

Inflammation and oxidative stress are the root causes of all kinds of diseases at certain level ranges, from flu to all chronic diseases. Reactive oxygen species, hydroxyl, and free iron, along with other free radicals, are normally produced in every cell of the body during normal metabolism. Toxins come with the normal diet eaten by a person. These toxins can contribute to an imbalance between the pro-oxidant and antioxidant level. This condition leads to various diseases. Antioxidants protect from the damage of free radicles and prevent metabolic and chronic conditions. They protect from inflammation and reduce the burden of disease by lowering the risk of pathogen attacks. Phenols and flavonoids are powerful antioxidants that prevent all kinds of free radicals, and N. sativa contain a variety of antioxidants [170,171]. In Virto research explains the different antioxidant activities of different extracts containing phenolic compounds. Another study showed syringic acid, p-coumaric acid, thymoquinone, and Vitamin E. The antioxidant effect of the black seed extracts contained astonishing usage in the traditional and alternative medicine [172]. Black cumin was used for the low testosterone level by ancient Arabic people. Black seed oil can improve muscle mass and stamina, as well as increase testosterone levels. These properties make this oil a treatment for infertility [173]. Aging can cause prostate enlargement and become a reason of urine incontinency among old age males. Black seed oil can treat prostatitis and provide relief from this condition [174].

7. Conclusions

There is a lot of evidence showing that black seed, black seed oil, and its active constituents have effective anti-oxidant, -microbial, -parasite, -viral, -fungal, -inflammation, and -diabetics properties against many disorders in humans and animals—it is a relatively safe food, with a long, remarkable history in the traditional medicinal system. It can be used as a drug in the pharmaceutical and nutraceutical industries, due to its anti-microbial properties. It is suggested that a new drug can be characterized and developed from the active ingredients of the black seed. For this purpose, researchers and scientists can apply many new technologies to reach that goal. Experimental or clinical research work is needed to further assess the effects on the body. Furthermore, industries should change their attitudes and strategies and invest in natural compounds that have great potential, according to their biological properties.

Acknowledgments

This research did not receive any specific grant from funding agencies in the public, commercial, or non-profit sectors.

Author Contributions

Conceptualization, M.A.R. and M.I.; methodology, W.K.; software, H.K.; validation, A.S. and A.E.; formal analysis, W.K., N.I. and I.M.; investigation, A.A.-F., G.S. and A.A.E.; data curation, W.S.A. and A.N.; writing—original draft preparation, M.A.R. and W.K.; writing—review and editing, M.U.N., M.I., W.K., M.A.R. and H.K. supervision, W.K. and M.U.N.; project administration, M.A.R.; funding acquisition, A.A.-F., G.S. and A.A.E. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data it is availability within this study.

Conflicts of Interest

The authors declare no conflict of interest.

Funding Statement

This research received no external funding.

Footnotes

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  • 1.Huchchannanavar S., Yogesh L.N., Prashant S.M. The black seed Nigella sativa: A wonder seed. Int. J. Chem. Stud. 2019;7:1320–1324. [Google Scholar]
  • 2.Sands R.D., Suttles S.A. World agricultural baseline scenarios through 2050. Appl. Econ. Perspect. Policy. 2022 doi: 10.1002/aepp.13309. [DOI] [Google Scholar]
  • 3.Goreja W.G. Black seed. Nature’s Miracle Remedy. Karger Publishers; Basel, Switzerland: 2003. [Google Scholar]
  • 4.Ahmad A., Husain A., Mujeeb M., Khan S.A., Najmi A.K., Siddique N.A., Damanhouri Z.A., Anwar F. A Review on Therapeutic Potential of Nigella sativa: A Miracle Herb. Asian Pac. J. Trop. Biomed. 2013;3:337–352. doi: 10.1016/S2221-1691(13)60075-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Warrier P.K., Nambiar V.P.K., Ramankutty C. Indian Medicinal Plants: A Compendium of 500 Species. Orient Blackswan; Hyderabad, India: 2004. p. 4. [Google Scholar]
  • 6.Al-Khalaf M.I., Ramadan K.S. Antimicrobial and Anticancer Activity of Nigella sativa Oil—A Review. Aus. J. Basic Appl. Sci. 2013;7:505–514. [Google Scholar]
  • 7.El-Mahdy M.A., Zhu Q., Wang Q.E., Wani G., Wani A.A. Thymoquinone Induces Apoptosis through Activation of Caspase-8 and Mitochondrial Events in P53-Null Myeloblastic Leukemia Hl-60 Cells. Int. J. Cancer. 2005;117:409–417. doi: 10.1002/ijc.21205. [DOI] [PubMed] [Google Scholar]
  • 8.Salomi M.J., Satish C.N., Panikkar K.R. Inhibitory Effects of Nigella sativa and Saffron (Crocus sativus) on Chemical Carcinogenesis in Mice. Nutr. Cancer. 1991;16:67–72. doi: 10.1080/01635589109514142. [DOI] [PubMed] [Google Scholar]
  • 9.Effenberger K., Breyer S., Schobert R. Terpene Conjugates of the Nigella sativa Seed-Oil Constituent Thymoquinone with Enhanced Efficacy in Cancer Cells. Chem. Biodivers. 2010;7:129–139. doi: 10.1002/cbdv.200900328. [DOI] [PubMed] [Google Scholar]
  • 10.Chehl N., Chipitsyna G., Gong Q., Yeo C.J., Arafat H.A. Anti-Inflammatory Effects of the Nigella sativa Seed Extract, Thymoquinone, in Pancreatic Cancer Cells. HPB. 2009;11:373–381. doi: 10.1111/j.1477-2574.2009.00059.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Thabrew M.I., Mitry R.R., Morsy M.A., Hughes R.D. Cytotoxic Effects of a Decoction of Nigella sativa, Hemidesmus indicus and Smilax glabra on Human Hepatoma Hepg2 Cells. Life Sci. 2005;77:1319–1330. doi: 10.1016/j.lfs.2005.01.022. [DOI] [PubMed] [Google Scholar]
  • 12.Yi T., Cho S.G., Yi Z., Pang X., Rodriguez M., Wang Y., Sethi G., Aggarwal B.B., Liu M. Thymoquinone Inhibits Tumor Angiogenesis and Tumor Growth Through Suppressing AKT and Extracellular Signal-Regulated Kinase Signaling Pathways. Mol. Cancer Ther. 2008;7:1789–1796. doi: 10.1158/1535-7163.MCT-08-0124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Khan N., Sultana S. Inhibition of Two Stage Renal Carcinogenesis, Oxidative Damage and Hyperproliferative Response by Nigella sativa. Eur. J. Cancer Prev. 2005;14:159–168. doi: 10.1097/00008469-200504000-00012. [DOI] [PubMed] [Google Scholar]
  • 14.Leong X.F., Mustafa M., Jaarin K. Nigella sativa and Its Protective Role in Oxidative Stress and Hypertension. Evid.-Based Complement. Altern. Med. 2013;2013:120732. doi: 10.1155/2013/120732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.El-Dakhakhny M. Effects of Nigella sativa Oil on Gastric Secretion and Ethanol Induced Ulcer in Rats. J. Ethnopharmacol. 2000;72:299–304. doi: 10.1016/S0378-8741(00)00235-X. [DOI] [PubMed] [Google Scholar]
  • 16.Hosseinzadeh H., Parvardeh S., Nassiri-Asl M., Mansouri M.T. Intracerebroventricular Administration of Thymoquinone, the Major Constituent of Nigella sativa Seeds, Suppresses Epileptic Seizures in Rats. Med. Sci. Monit. 2005;11:110. [PubMed] [Google Scholar]
  • 17.Khonche A. Effectiveness of Nigella sativa Oil on Patients with Nonalcoholic Fatty Liver: A Randomized Double-Blind Placebo-Controlled Trial. Acad. J. Med. Plants. 2018;6:307–312. [Google Scholar]
  • 18.Koshak A. Nigella sativa Supplementation Improves Asthma Control and Biomarkers: A Randomized, Double-Blind, Placebo-Controlled Trial. Phytother. Res. 2017;31:403–409. doi: 10.1002/ptr.5761. [DOI] [PubMed] [Google Scholar]
  • 19.Azizi F., Ghorat F., Rakhshani M.H., Rad M. Comparison of the Effect of Topical Use of Nigella sativa Oil and Diclofenac Gel on Osteoarthritis Pain in Older People: A Randomized, Double-Blind, Clinical Trial. J. Herb. Med. 2019;16:100259. doi: 10.1016/j.hermed.2019.100259. [DOI] [Google Scholar]
  • 20.Tavakkoli A. Review on Clinical Trials of Black Seed (Nigella sativa) and Its Active Constituent, Thymoquinone. J. Pharmacopunct. 2017;20:179–193. doi: 10.3831/KPI.2017.20.021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Majdalawieh A.F., Fayyad M.W., Nasrallah G.K. Anti-Cancer Properties and Mechanisms of Action of Thymoquinone, the Major Active Ingredient of Nigella sativa. Crit. Rev. Food Sci. Nutr. 2017;57:3911–3928. doi: 10.1080/10408398.2016.1277971. [DOI] [PubMed] [Google Scholar]
  • 22.Abdulelah H.A.A., Zainal-Abidin B.A.H. In Vivo Anti-Malarial Tests of Nigella sativa (Black Seed) Different Extracts. Am. J. Pharmacol. Toxicol. 2007;2:46–50. [Google Scholar]
  • 23.Okeola V.O., Adaramoye O.A., Nneji C.M., Falade C.O., Farombi E.O., Ademowo O.G. Antimalarial and Antioxidant Activities of Methanolic Extract of Nigella sativa Seeds (Black Cumin) in Mice Infected with Plasmodium yoelli nigeriensis. Parasitol. Res. 2011;108:1507–1512. doi: 10.1007/s00436-010-2204-4. [DOI] [PubMed] [Google Scholar]
  • 24.Bashmail H.A. Thymoquinone Synergizes Gemcitabine Anti-Breast Cancer Activity Via Modulating Its Apoptotic and Autophagic Activities. Sci. Rep. 2018;8:11674. doi: 10.1038/s41598-018-30046-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Salem M.L. Immunomodulatory and therapeutic properties of the Nigella sativa seed. Int. Immunopharmacol. 2005;5:1749–1770. doi: 10.1016/j.intimp.2005.06.008. [DOI] [PubMed] [Google Scholar]
  • 26.Nautiyal O.H. Fruit Oils: Chemistry and Functionality. Springer; Cham, Switzerland: 2019. Black seed (Nigella sativa) oil; pp. 839–857. [Google Scholar]
  • 27.Ojueromi O.O., Oboh G., Ademosun A.O. Effect of black seeds (Nigella sativa) on inflammatory and immunomodulatory markers in Plasmodium berghei-infected mice. J. Food Biochem. 2022:e14300. doi: 10.1111/jfbc.14300. [DOI] [PubMed] [Google Scholar]
  • 28.Janfaza S., Janfaza E. The Study of Pharmacologic and Medicinal Valuation of Thymoquinone of Oil of Nigella sativa in the Treatment of Diseases. Ann. Biol. Res. 2001;23:1953–1957. [Google Scholar]
  • 29.Ahmad I., Tripathi J., Sharma M. Nigella sativa—A Medicinal Herb with Immense Therapeutic Potential (A Systematic Review) Int. J. Biol. Pharm. Res. 2014;5:755–762. [Google Scholar]
  • 30.Takruri H.R., Dameh M.A. Study of the Nutritional Value of Black Cumin Seeds (Nigella sativa) J. Sci. Food. Agric. 1998;76:404–410. doi: 10.1002/(SICI)1097-0010(199803)76:3<404::AID-JSFA964>3.0.CO;2-L. [DOI] [Google Scholar]
  • 31.Hosseini M., Zakeri S., Khoshdast S. The Effects of Nigella sativa Hydro-Alcoholic Extract and Thymoquinone on Lipopolysaccharide-Induced Depression like Behavior in Rats. J. Pharm. Bioallied Sci. 2012;4:219–225. doi: 10.4103/0975-7406.99052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Rajsekhar S., Kuldeep B. Pharmacognosy and Pharmacology of Nigella sativa—A Review. Int. Res. J. Pharm. 2011;2:36–39. [Google Scholar]
  • 33.Paarakh P.M. Nigella sativa Linn.—A comprehensive review. Indian J. Nat. Prod. Resour. 2010;1:409–429. [Google Scholar]
  • 34.Burdock G.A. Assessment of black cumin (Nigella sativa) as a food ingredient and putative therapeutic agent. Regul. Toxicol. Pharmacol. 2022;128:105088. doi: 10.1016/j.yrtph.2021.105088. [DOI] [PubMed] [Google Scholar]
  • 35.Hajhashemi V., Ghannadi A., Jafarabadi H. Black Cumin Seed Essential Oil, As A Potent Analgesic and Anti-inflammatory Drug. Phytother. Res. 2004;18:195–199. doi: 10.1002/ptr.1390. [DOI] [PubMed] [Google Scholar]
  • 36.Rastogi R.P., Mehrotra B.N. Compendium of Indian Medicinal Plants. Reprinted ed. Volume 3. Central Drug Research Institute; Lucknow, India: 1993. pp. 452–453. [Google Scholar]
  • 37.Nickavar B., Mojab F., Javidnia K., Amoli M.A. Chemical Composition of the Fixed and Volatile Oils of Nigella sativa from Iran. Z. Naturforsch. C. 2003;58:629–631. doi: 10.1515/znc-2003-9-1004. [DOI] [PubMed] [Google Scholar]
  • 38.Gali-Muhtasib H., El-Najjar N., Schneider-Stock R. The Medicinal Potential of Black Seed (Nigella sativa) and Its Components. Adv. Phytomed. 2006;2:133–153. [Google Scholar]
  • 39.Mohsen Z.A., Gheni S.W., Hussein J.M. Study of The Effect of Black Seed Extract in Some Bacteria That Cause Urinary Tract Infection. J. Kerbala Univ. 2009;7:156–160. [Google Scholar]
  • 40.Tulukcu F. A Comparative Study on Fatty Acid Composition of Black Cumin Obtained from Different Regions of Turkey, Iran and Syria. Afr. J. Agric. Res. 2011;6:892–895. [Google Scholar]
  • 41.Hobbenaghi R., Javanbakht J., Sadeghzadeh S.H., Kheradmand D., Abdi F., Jaberi M., Mohammadiyan M., Khadivar F., Mollaei Y. Neuroprotective Effects of Nigella sativa Extract on Cell Death in Hippocampal Neurons Following Experimental Global Cerebral Ischemia-Reperfusion Injury in Rats. J. Neuro Sci. 2014;337:74–79. doi: 10.1016/j.jns.2013.11.019. [DOI] [PubMed] [Google Scholar]
  • 42.Develi S., Evran B., Kalaz E., Koçak-Toker N., Erata G. Protective Effect of Nigella sativa Oil Against Binge Ethanol-Induced Oxidative Stress and Liver Injury in Rats. Chin. J. Nat. Med. 2014;12:495–499. doi: 10.1016/S1875-5364(14)60077-7. [DOI] [PubMed] [Google Scholar]
  • 43.Sultan M., Butt M., Karim R., Ahmad A., Suleria H., Saddique M. Toxicological and Safety Evaluation of Nigella sativa Lipid and Volatile Fractions in Streptozotocin Induced Diabetes Mellitus. Asian Pac. J. Trop. Dis. 2014;4:S693–S697. doi: 10.1016/S2222-1808(14)60709-X. [DOI] [Google Scholar]
  • 44.Kamil Z.H. Spectacular Black Seeds (Nigella sativa) Medical Importance Review. Med. J. Babylon. 2013;10:1–9. [Google Scholar]
  • 45.Al-Zendi S.K.J., Jasim A.N., AL-Mousawi A.H. The Effect of Hot Water and Ethanol Extract of Nigella sativa in Immune System of Albino Mice. Um Salamah J. Sci. 2009;6:235–243. [Google Scholar]
  • 46.Sharma N., Ahirwar D., Jhade D. Medicinal and pharmacological potential of Nigella sativa: A review. Ethnobot. Rev. 2009;13:946–955. [Google Scholar]
  • 47.Khan M.A., Afzal M. Chemical Composition of Nigella sativa Linn: Part 2 Recent Advances. Inflammopharmacology. 2016;24:67–79. doi: 10.1007/s10787-016-0262-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Agbaria R., Gabarin A., Dahan A., Ben-Shabat S. Anti-Cancer Activity of Nigella sativa (Black Seed) and Its Relationship with the Thermal Processing and Quinine Composition of the Seeds. Drug Des. Dev. Ther. 2015;9:3119–3124. doi: 10.2147/DDDT.S82938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Miguel G.A., Jacobsen C., Prieto C., Kempen P.J., Lagaron J.M., Chronakis I.S., García-Moreno P.J. Oxidative Stability and Physical Properties of Mayonnaise Fortified with Zein Electrosprayed Capsules Loaded with Fish Oil. J. Food Eng. 2019;263:348–358. doi: 10.1016/j.jfoodeng.2019.07.019. [DOI] [Google Scholar]
  • 50.Abdel-Razek A.G., Badr A.N., El-Messery T.M., El-Said M.M., Hussein A.M.S. Micro-Nano Encapsulation of Black Seed Oil Ameliorate Its Characteristics and Its Mycotoxin Inhibition. Biosci. Res. 2018;3:2591–2601. [Google Scholar]
  • 51.Edris A.E., Kalemba D., Adamiec J., Piatkowski M. Microencapsulation of Nigella sativa Oleoresin by Spray Drying for Food and Nutraceutical Applications. Food Chem. 2016;204:326–333. doi: 10.1016/j.foodchem.2016.02.143. [DOI] [PubMed] [Google Scholar]
  • 52.Kiralan M., Özkan G., Bayrak A., Ramadan M.F. Physicochemical properties and stability of black cumin (Nigella sativa) seed oil as affected by different extraction methods. Indus. Crops Prod. 2014;57:52–58. doi: 10.1016/j.indcrop.2014.03.026. [DOI] [Google Scholar]
  • 53.Mohammed N.K., Manap A., Yazid M., Tan C.P., Muhialdin B.J., Alhelli A.M., Meor Hussin A.S. The Effects of Different Extraction Methods on Antioxidant Properties, Chemical Composition, and Thermal Behavior of Black Seed (Nigella sativa) Oil. Evid.-Based Comp. Altern. Med. 2016;2016:6273817. doi: 10.1155/2016/6273817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Rao M.V., Al-Marzouqi A.H., Kaneez F.S., Ashraf S.S., Adem A. Comparative evaluation of SFE and solvent extraction methods on the yield and composition of black seeds (Nigella sativa) J. Liq. Chromatogr. Relat. Technol. 2007;30:2545–2555. doi: 10.1080/10826070701540100. [DOI] [Google Scholar]
  • 55.Dinagaran S., Sridhar S., Eganathan P. Chemical Composition and Antioxidant Activities of Black Seed Oil (Nigella sativa) Int. J. Pharm. Sci. Res. 2016;7:44–73. [Google Scholar]
  • 56.Kokoska L., Havlik J., Valterova I., Sovova H., Sajfrtova M., Jankovska I. Comparison of Chemical Composition and Antibacterial Activity of Nigella sativa Seed Essential Oils Obtained by Different Extraction Methods. J. Food Prot. 2008;71:2475–2480. doi: 10.4315/0362-028X-71.12.2475. [DOI] [PubMed] [Google Scholar]
  • 57.Burits M., Bucar F. Antioxidant Activity of Nigella sativa Essential Oil. Phytother. Res. 2000;14:323–328. doi: 10.1002/1099-1573(200008)14:5<323::AID-PTR621>3.0.CO;2-Q. [DOI] [PubMed] [Google Scholar]
  • 58.Abedi A.S., Rismanchi M., Shahdoostkhany M., Mohammadi A., Mortazavian A.M. Microwave-Assisted Extraction of Nigella sativa Essential Oil and Evaluation of Its Antioxidant Activity. J. Food Sci. Technol. 2017;54:3779–3790. doi: 10.1007/s13197-017-2718-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Moghimi M., Farzaneh V., Bakhshabadi H. The Effect of Ultrasound Pretreatment on Some Selected Physicochemical Properties of Black Cumin (Nigella sativa) Nutrire. 2018;43:18. doi: 10.1186/s41110-018-0077-y. [DOI] [Google Scholar]
  • 60.Sabriu-Haxhijaha A., Popovska O., Mustafa Z. Thin-Layer Chromatography Analysis of Nigella sativa Essential Oil. J. Hyg. Eng. Des. 2020;31:152–156. [Google Scholar]
  • 61.Ahmad R., Ahmad N., Shehzad A. Solvent and Temperature Effects of Accelerated Solvent Extraction (ASE) Coupled with Ultra-High Pressure Liquid Chromatography (UHPLC-DAD) Technique for Determination of Thymoquinone in Commercial Food Samples of Black Seeds (Nigella sativa) Food Chem. 2020;309:125740. doi: 10.1016/j.foodchem.2019.125740. [DOI] [PubMed] [Google Scholar]
  • 62.Gharby S., Harhar H., Guillaume D., Roudani A., Boulbaroud S., Ibrahimi M., Charrouf Z. Chemical Investigation of Nigella sativa Seed Oil Produced in Morocco. J. Saudi Soc. Agric. Sci. 2015;14:172–177. doi: 10.1016/j.jssas.2013.12.001. [DOI] [Google Scholar]
  • 63.Amin S., Mir S.R., Kohli K., Ali B., Ali M. A Study of the Chemical Composition of Black Cumin Oil and Its Effect on Penetration Enhancement from Transdermal Formulations. Nat. Prod. Res. 2010;24:1151–1157. doi: 10.1080/14786410902940909. [DOI] [PubMed] [Google Scholar]
  • 64.Kaskoos R.A. Fatty Acid Composition of Black Cumin Oil from Iraq. Res. J. Med. Plant. 2011;5:85–89. doi: 10.3923/rjmp.2011.85.89. [DOI] [Google Scholar]
  • 65.Soleimanifar M., Niazmand R., Jafari S.M. Evaluation of Oxidative Stability, Fatty Acid Profile, and Antioxidant Properties of Black Cumin Seed Oil and Extract. J Food Meas. Charact. 2019;13:383–389. doi: 10.1007/s11694-018-9953-7. [DOI] [Google Scholar]
  • 66.Farhan N., Salih N., Salimon J. Physiochemical Properties of Saudi Nigella sativa (‘Black Cumin’) Seed Oil. OCL. 2021;28:11. doi: 10.1051/ocl/2020075. [DOI] [Google Scholar]
  • 67.Khan A., Rehman M.U., editors. Black Seeds (Nigella sativa): Pharmacological and Therapeutic Applications. Elsevier; Amsterdam, The Netherlands: 2021. pp. 29–62. [Google Scholar]
  • 68.Fonseca W.F., Ahluwalia P., Bhatt D.N., Ansari S., Tabassum R., Vaibhav K., Ahluwalia M. Black Seeds (Nigella sativa) Elsevier; Amsterdam, The Netherlands: 2022. Black seed (Nigella sativa): Pharmacological and therapeutic applications in endocrine dysfunction; pp. 405–422. [Google Scholar]
  • 69.Babayan V.K., Koottungal D., Halaby G.A. Proximate Analysis, Fatty Acid and Amino Acid Composition of Nigella sativa Seeds. J. Food Sci. 1978;43:1314–1315. doi: 10.1111/j.1365-2621.1978.tb15297.x. [DOI] [Google Scholar]
  • 70.Nergiz C., Ötleş S. Chemical Composition of Nigella sativa Seeds. Food Chem. 1993;48:259–261. doi: 10.1016/0308-8146(93)90137-5. [DOI] [Google Scholar]
  • 71.Cheikh-Rouhou S. Nigella sativa: Chemical Composition and Physicochemical Characteristics of Lipid Fraction. Food Chem. 2007;101:673–681. doi: 10.1016/j.foodchem.2006.02.022. [DOI] [Google Scholar]
  • 72.Saleh F.A., El-Darra N., Raafat K., El Ghazzawi I. Phytochemical analysis of Nigella sativa Utilizing GC-MS exploring its antimicrobial effects against multidrug-resistant bacteria. Pharmacogn. J. 2018;10:99–105. doi: 10.5530/pj.2018.1.18. [DOI] [Google Scholar]
  • 73.Matthaus B., Özcan M.M. Fatty Acids, Tocopherol, and Sterol Contents of Some Nigella Species Seed Oil. Czech J. Food Sci. 2011;29:145–150. doi: 10.17221/206/2008-CJFS. [DOI] [Google Scholar]
  • 74.Khoddami A. Physicochemical Characteristics of Nigella Seed (Nigella sativa) Oil as Affected by Different Extraction Methods. J. Am. Oil Chem. Soc. 2011;88:533–540. doi: 10.1007/s11746-010-1687-6. [DOI] [Google Scholar]
  • 75.Alehosseini A. Electrospun Curcumin-Loaded Protein Nanofiber Mats as Active/Bioactive Coatings for Food Packaging Applications. Food Hydrocoll. 2019;87:758–771. doi: 10.1016/j.foodhyd.2018.08.056. [DOI] [Google Scholar]
  • 76.Sun-Waterhouse D., Zhou J., Miskelly G., Wibisono R., Wadhwa S. Stability of Encapsulated Olive Oil in The Presence of Caffeic Acid. Food Chem. 2001;126:1049–1056. doi: 10.1016/j.foodchem.2010.11.124. [DOI] [Google Scholar]
  • 77.Moomand K., Lim L. Oxidative Stability of Encapsulated Fish Oil in Electrospun Zein Fibres. Food Res. Int. 2014;62:523–532. doi: 10.1016/j.foodres.2014.03.054. [DOI] [Google Scholar]
  • 78.Lutterodt H., Luther M., Slavin M., Yin J., Parry J., Gao J., Yu L. Fatty Acid Profile, Thymoquinone Content, Oxidative Stability and Antioxidant Properties of Cold-Pressed Black Cumin Seed Oils. LWT Food Sci. Technol. 2010;43:1409–1413. doi: 10.1016/j.lwt.2010.04.009. [DOI] [Google Scholar]
  • 79.Ghosh S., Sarkar T., Das A., Chakraborty R. Micro and nanoencapsulation of natural colors: A holistic view. Appl. Biochem. Biotechnol. 2021;193:3787–3811. doi: 10.1007/s12010-021-03631-8. [DOI] [PubMed] [Google Scholar]
  • 80.Ravindran J., Nair H.B., Sung B., Prasad S., Tekmal R.R., Aggarwal B.B. RETRACTED: Thymoquinone Poly (Lactide-Co-Glycolide) Nanoparticles Exhibit Enhanced Anti-Proliferative, Anti-Inflammatory, and Chemosensitization Potential. Biochem. Pharmacol. 2010;79:1640–1647. doi: 10.1016/j.bcp.2010.01.023. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  • 81.Badri W., Asbahani A.E., Miladi K., Baraket A., Agustia G., Nazari Q.A., Errachid A., Fessi H., Elaissari A. Poly (Ε-Caprolactone) Nanoparticles Loaded with Indomethacin and Nigella sativa Essential Oil for the Topical Treatment of Inflammation. J. Drug Deliv. Sci. Technol. 2018;46:234–242. doi: 10.1016/j.jddst.2018.05.022. [DOI] [Google Scholar]
  • 82.Dordevic V., Balanc B., Belscak-Cvitanovic A., Levic S., Trifkovic K., Kalusevic A., Kostic I., Komes D., Bugarski B., Nedovic V. Trends in Encapsulation Technologies for Delivery of Food Bioactive Compounds. Food Eng. Rev. 2015;7:452–490. doi: 10.1007/s12393-014-9106-7. [DOI] [Google Scholar]
  • 83.Jacobsen C., García-Moreno P.J., Mendes A.C., Mateiu R.V., Chronakis I.S. Use of Electrohydrodynamic Processing for Encapsulation of Sensitive Bioactive Compounds and Applications in Food. Ann. Rev. Food Sci. Technol. 2018;9:525–549. doi: 10.1146/annurev-food-030117-012348. [DOI] [PubMed] [Google Scholar]
  • 84.García-Moreno P.J., Mendes A.C., Jacobsen C., Chronakis I.S. Polymers for Food Applications. Springer; Berlin/Heidelberg, Germany: 2018. Biopolymers for the Nano-Microencapsulation of Bioactive Ingredients by Electrohydrodynamic Processing; pp. 447–479. [Google Scholar]
  • 85.Altan A., Aytac Z., Uyar T. Carvacrol Loaded Electrospun Fibrous Films from Zein and Poly (Lactic Acid) for Active Food Packaging. Food Hydrocoll. 2018;81:48–59. doi: 10.1016/j.foodhyd.2018.02.028. [DOI] [Google Scholar]
  • 86.Lagaron J.M., Castro S., Galan D., Valle J.M. Instalación y Procedimiento de Encapsulado Industrial de Sustancias Termolábiles. ES-2674808_A1. Spain Patent. 2019 April 11;
  • 87.Busolo M.A., Torres-Giner S., Prieto C., Lagaron J.M. Electrospraying Assisted by Pressurized Gas as an Innovative High-Throughput Process for the Microencapsulation and Stabilization of Docosahexaenoic Acid-Enriched Fish Oil in Zein Prolamine. Innov. Food Sci. Emerg. Technol. 2018;51:12–19. doi: 10.1016/j.ifset.2018.04.007. [DOI] [Google Scholar]
  • 88.Chan E.S. Preparation of Ca-Alginate Beads Containing High Oil Content: Influence of Process Variables on Encapsulation Efficiency and Bead Properties. Carbohydr. Polym. 2011;84:1267–1275. doi: 10.1016/j.carbpol.2011.01.015. [DOI] [Google Scholar]
  • 89.Jafari S.M., Assadpoor E., He Y., Bhandari B. Encapsulation Efficiency of Food Flavours and Oils during Spray Drying. Dry Technol. 2008;26:816–835. doi: 10.1080/07373930802135972. [DOI] [Google Scholar]
  • 90.Martins I.M., Barreiro M.F., Coelho M., Rodrigues A.E. Microencapsulation of Essential Oils with Biodegradable Polymeric Carriers for Cosmetic Applications. Chem. Eng. J. 2014;245:191–200. doi: 10.1016/j.cej.2014.02.024. [DOI] [Google Scholar]
  • 91.Singh M.N., Hemant K.S.Y., Ram M., Shivakumar H.G. Microencapsulation: A Promising Technique for Controlled Drug Delivery. Res. Pharm. Sci. 2010;2:65. [PMC free article] [PubMed] [Google Scholar]
  • 92.Wan L.Q., Jiang J., Arnold D.E., Guo X.E., Lu H.H., Mow V.C. Calcium Concentration Effects on the Mechanical and Biochemical Properties of Chondrocyte-Alginate Constructs. Cell. Mol. Bioeng. 2008;1:93–102. doi: 10.1007/s12195-008-0014-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 93.Husain O., Lau W., Edirisinghe M., Parhizkar M. Investigating the Particle to Fibre Transition Threshold during Electrohydrodynamic Atomization of a Polymer Solution. Mater. Sci. Eng. C. 2016;65:240–250. doi: 10.1016/j.msec.2016.03.076. [DOI] [PubMed] [Google Scholar]
  • 94.Xie J., Jiang J., Davoodi P., Srinivasan M.P., Wang C.H. Electrohydrodynamic Atomization: A Two-Decade Effort to Produce and Process Micro-/Nanoparticulate Materials. Chem. Eng. Sci. 2015;125:32–57. doi: 10.1016/j.ces.2014.08.061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 95.Baimark Y., Srisuwan Y. Preparation of Alginate Microspheres by Waterin-Oil Emulsion Method for Drug Delivery: Effect of Ca2+ Post-Cross-Linking. Adv. Powder Technol. 2014;25:1541–1546. doi: 10.1016/j.apt.2014.05.001. [DOI] [Google Scholar]
  • 96.Alkhatib H., Mohamed F., Akkawi M.E., Alfatama M., Chatterjee B. Microencapsulation of Black Seed Oil in Alginate Beads for Stability and Taste Masking. J. Drug Deliv. Sci. Technol. 2020;60:102030. doi: 10.1016/j.jddst.2020.102030. [DOI] [Google Scholar]
  • 97.Li X.Y., Zheng Z.B., Yu D.G., Liu X.K., Qu Y.L., Li H.L. Electrosprayed Sperical Ethylcellulose Nanoparticles for an Improved Sustained-Release Profile of Anticancer Drug. Cellulose. 2017;24:5551–5564. doi: 10.1007/s10570-017-1498-0. [DOI] [Google Scholar]
  • 98.Wu Y., MacKay J.A., McDaniel J.R., Chilkoti A., Clark R.L. Fabrication of Elastin-Like Polypeptide Nanoparticles for Drug Delivery by Electrospraying. Biomacromolecules. 2008;10:19–24. doi: 10.1021/bm801033f. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 99.Liu Z.P., Zhang Y.Y., Yu D.G., Wu D., Li H.L. Fabrication of Sustained-Release Zein Nanoparticles via Modified Coaxial Electrospraying. Chem. Eng. J. 2018;334:807–816. doi: 10.1016/j.cej.2017.10.098. [DOI] [Google Scholar]
  • 100.Fernandes B., Borges V., Botrel A. Gum Arabic/Starch/Maltodextrin/Inulin as Wall Materials on the Microencapsulation of Rosemary Essential Oil. Carbohydr. Polym. 2014;101:524–532. doi: 10.1016/j.carbpol.2013.09.083. [DOI] [PubMed] [Google Scholar]
  • 101.Carneiro H., Tonon R., Grosso C., Hubinger M. Encapsulation Efficiency and Oxidative Stability of Flaxseed Oil Microencapsulated by Spray drying Using Different Combinations of Wall Materials. J. Food Eng. 2013;115:443–451. doi: 10.1016/j.jfoodeng.2012.03.033. [DOI] [Google Scholar]
  • 102.Koç M., Güngör O., Zungur A., Yalçın B., Selek İ., Ertekin F., Ötles S. Microencapsulation of Extra Virgin Olive Oil by Spray Drying: Effect of Wall Materials Composition, Process Conditions, and Emulsification Method. Food Bioprocess Technol. 2015;8:301–318. doi: 10.1007/s11947-014-1404-9. [DOI] [Google Scholar]
  • 103.Botrel A., Fernandes B., Borges V., Yoshida I. Influence of Wall Matrix Systems on the Properties of Spray-Dried Microparticles Containing Fish Oil. Food Res. Int. 2014;62:344–352. doi: 10.1016/j.foodres.2014.02.003. [DOI] [Google Scholar]
  • 104.Gallardo G., Guida L., Martinez V., López M., Bernhardt D., Blasco R., Pedroza-Islas R., Hermida L. Microencapsulation of Linseed Oil by Spray Drying for Functional Food Application. Food Res. Int. 2013;52:473–482. doi: 10.1016/j.foodres.2013.01.020. [DOI] [Google Scholar]
  • 105.Sedaghat D.A., Nikbakht N.M., Kassozi V., Nakisozi H., Van D., Meeren P. Recent Advances in Food Colloidal Delivery Systems for Essential Oils and their Main Components. Trends Food Sci. Technol. 2020;99:474–486. doi: 10.1016/j.tifs.2020.03.037. [DOI] [Google Scholar]
  • 106.Bajpai P. Colloid and Surface Chemistry. Biermann’s Handbook of Pulp and Paper. Elsevier Inc.; Amsterdam, The Netherlands: 2018. pp. 381–400. [Google Scholar]
  • 107.Gibbs B.F., Kermasha S., Alli I., Mulligan C.N. Encapsulation in the Food Industry: A Review. Int. J. Food Sci. Nutr. 1999;50:213–224. doi: 10.1080/096374899101256. [DOI] [PubMed] [Google Scholar]
  • 108.Sajid M., Cameotra S.S., Ahmad Khan M.S., Ahmad I. New Look to Phytomedicine: Advancements in Herbal Products as Novel Drug Leads. Elsevier; Amsterdam, The Netherlands: 2018. Nanoparticle-Based Delivery of Phytomedicines: Challenges and Opportunities; pp. 597–623. [Google Scholar]
  • 109.Mellema M., Van Benthum W.A.J., Boer B., Von Harras J., Visser A. Wax Encapsulation of Water-Soluble Compounds for Application in Foods. J. Microencapsul. 2006;23:729–740. doi: 10.1080/02652040600787900. [DOI] [PubMed] [Google Scholar]
  • 110.Alliod O., Valour J.P., Urbaniak S., Fessi H., Dupin D., Charcosset C. Preparation of Oil-In-Water Nanoemulsions at Large-Scale Using Premix Membrane Emulsification and Shirasu Porous Glass (SPG) Membranes. Colloids Surf. A. 2018;557:76–84. doi: 10.1016/j.colsurfa.2018.04.045. [DOI] [Google Scholar]
  • 111.Rahim M.A., Imran M., Khan M.K., Ahmad M.H., Ahmad R.S. Impact of spray drying operating conditions on encapsulation efficiency, oxidative quality, and sensorial evaluation of chia and fish oil blends. J. Food Process. Preserv. 2022;46:e16248. doi: 10.1111/jfpp.16248. [DOI] [Google Scholar]
  • 112.Zhou Y., Sun S., Bei W., Zahi M.R., Yuan Q., Liang H. Preparation and Antimicrobial Activity of Oregano Essential Oil Pickering Emulsion Stabilized by Cellulose Nanocrystals. Int. J. Biol. Macromol. 2018;112:7–13. doi: 10.1016/j.ijbiomac.2018.01.102. [DOI] [PubMed] [Google Scholar]
  • 113.Sharma M., Mann B., Sharma R., Bajaj R., Athira S., Sarkar P., Pothuraju R. Sodium Caseinate Stabilized Clove Oil Nanoemulsion: Physicochemical Properties. J. Food Eng. 2017;212:38–46. doi: 10.1016/j.jfoodeng.2017.05.006. [DOI] [Google Scholar]
  • 114.Reis D.R., Ambrosi A.D., Luccio M. Encapsulated Essential Oils: A Perspective in Food Preservation. Future Foods. 2022;5:100126. doi: 10.1016/j.fufo.2022.100126. [DOI] [Google Scholar]
  • 115.Veiga R.D.S.D., Aparecida D., Silva-Buzanello R., Corso M.P., Canan C. Essential Oils Microencapsulated Obtained by Spray Drying: A Review. J. Essent. Oil Res. 2019;31:457–473. doi: 10.1080/10412905.2019.1612788. [DOI] [Google Scholar]
  • 116.Pellicer J.A., Fortea M.I., Trabal J., Rodríguez-López M.I., Gabaldón J.A., Núñez-Delicado E. Stability of Microencapsulated Strawberry Flavour by Spray Drying, Freeze Drying and Fluid Bed. Powder Technol. 2019;347:179–185. doi: 10.1016/j.powtec.2019.03.010. [DOI] [Google Scholar]
  • 117.Fang Z., Bhandari B. Encapsulation of polyphenols—A review. Trends Food Sci. Technol. 2010;21:510–523. doi: 10.1016/j.tifs.2010.08.003. [DOI] [Google Scholar]
  • 118.Drusch S., Berg S. Extractable Oil in Microcapsules Prepared by Spray-Drying: Localisation, Determination and Impact on Oxidative Stability. Food Chem. 2008;109:17–24. doi: 10.1016/j.foodchem.2007.12.016. [DOI] [PubMed] [Google Scholar]
  • 119.Woo M.W., Bhandari B. Handbook of Food Powders: Processes and Properties. Elsevier Inc.; Amsterdam, The Netherlands: 2013. Spray Drying for Food Powder Production; pp. 29–56. [Google Scholar]
  • 120.Barrow C.J., Wang B., Adhikari B., Liu H. Spray Drying and Encapsulation of Omega-3 Oils. In: Jacobsen C., Nielsen N.S., Horn A.F., Sørensen A.D.M., editors. Food Enrichment with Mega-3 Fatty Acids. Woodhead Publishing Ltd.; Cambridge, UK: 2013. pp. 194–225. [Google Scholar]
  • 121.Costa S.S., Machado B.A.S., Martin A.R., Bagnara F., Ragadalli S.A., Alves A.R.C. Drying by Spray Drying in the Food Industry: Micro-Encapsulation, Process Parameters and Main Carriers Used. Afr. J. Food Sci. 2015;9:462–470. [Google Scholar]
  • 122.Bakry A.M., Abbas S., Ali B., Majeed H., Abouelwafa M.Y., Mousa A., Liang L. Microencapsulation of Oils: A Comprehensive Review of Benefits, Techniques, and Applications. Compr. Rev. Food Sci. Food Saf. 2016;15:143–182. doi: 10.1111/1541-4337.12179. [DOI] [PubMed] [Google Scholar]
  • 123.Gharsallaoui A., Roudaut G., Chambin O., Voilley A., Saurel R. Applications of Spray-Drying in Microencapsulation of Food Ingredients: An Overview. Food Res. Int. 2007;40:1107–1121. doi: 10.1016/j.foodres.2007.07.004. [DOI] [Google Scholar]
  • 124.Mohammed N.K., Tan C.P., Manap Y.A., Muhialdin B.J., Hussin A.S.M. Spray Drying for the Encapsulation of Oils—A Review. Molecules. 2020;25:3873. doi: 10.3390/molecules25173873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 125.Azad A.K., Al-Mahmood S.M.A., Chatterjee B., Sulaiman W.M.A., Elsayed T.M., Doolaanea A.A. Encapsulation of Black Seed Oil in Alginate Beads as A Ph-Sensitive Carrier for Intestine-Targeted Drug Delivery: In Vitro, In Vivo And Ex Vivo Study. Pharmaceutics. 2020;12:219. doi: 10.3390/pharmaceutics12030219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 126.Rushmi Z.T., Akter N., Mow R.J., Afroz M., Kazi M., Matas M., Shariare M.H. The Impact of Formulation Attributes and Process Parameters on Black Seed Oil Loaded Liposomes and their Performance in Animal Models of Analgesia. Saudi Pharm. J. 2017;25:404–412. doi: 10.1016/j.jsps.2016.09.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 127.Atay E., Altan A. Nanoencapsulation of Black Seed Oil by Coaxial Electrospraying: Characterisation, Oxidative Stability and In Vitro Gastrointestinal Digestion. Int. J. Food Sci. Technol. 2021;56:4526–4539. doi: 10.1111/ijfs.15209. [DOI] [Google Scholar]
  • 128.Karaman K. Characterization of Saccharomyces Cerevisiae Based Microcarriers for Encapsulation of Black Cumin Seed Oil: Stability of Thymoquinone and Bioactive Properties. Food Chem. 2020;313:126129. doi: 10.1016/j.foodchem.2019.126129. [DOI] [PubMed] [Google Scholar]
  • 129.Mukhtar H., Qureshi A.S., Anwar F., Mumtaz M.W., Marcu M. Nigella sativa seed and seed oil: Potential sources of high-value components for development of functional foods and nutraceuticals/pharmaceuticals. J. Essent. Oil Res. 2019;31:171–183. doi: 10.1080/10412905.2018.1562388. [DOI] [Google Scholar]
  • 130.Ghaznavi K. Tibb-I-Nabvi (Peace Be Upon Him) Aur Jadeed Science. Volume 1. Faisal Publishers; Lahore, Pakistan: 1988. pp. 231–232. [Google Scholar]
  • 131.Randhawa M.A., Alghamdi M.S. Anticancer Activity of Nigella sativa (Black Seed)—A Review. Am. J. Chin. Med. 2011;39:1075–1091. doi: 10.1142/S0192415X1100941X. [DOI] [PubMed] [Google Scholar]
  • 132.Bngels G., Brinckmann J. Nigella sativa Herbalgram. American Botanical Council; Austin, TX, USA: 2017. [Google Scholar]
  • 133.Miriam B. Is the World Ready for This Palestinian Dish? BBC News—Travel. [(accessed on 28 March 2019)]. Available online: scientificlib.com.
  • 134.Bramen L. Nigella Seeds: What the Heck Do I Do with Those? The Smithsonian Online. 2011. [(accessed on 4 January 2015)]. Available online: smithsonian.com.
  • 135.Hassanien M.F.R., Mahgoub S.A., El-Zahar K.M. Soft Cheese Supplemented with Black Cumin Oil: Impact on Food Borne Pathogens and Quality During Storage. Saudi J. Biol. Sci. 2014;21:280–288. doi: 10.1016/j.sjbs.2013.10.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 136.Anton N. Nano-emulsions and Nanocapsules by the PIT Method: An investigation on the Role of the Temperature Cycling on the Emulsion Phase Inversion. Int. J. Pharm. 2007;344:44–52. doi: 10.1016/j.ijpharm.2007.04.027. [DOI] [PubMed] [Google Scholar]
  • 137.Mahdi J., Yinghe S., Bhandari B. Nano-Emulsion Production by Sonication and Microfluidization—A Comparison. Int. J. Food Prop. 2006;9:475–485. doi: 10.1080/10942910600596464. [DOI] [Google Scholar]
  • 138.Mohammed N.K., Muhialdin B.J., Meor Hussin A.S. Characterization of nanoemulsion of Nigella sativa oil and its application in ice cream. Food Sci. Nutr. 2020;8:2608–2618. doi: 10.1002/fsn3.1500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 139.Depree J.A., Savage G.P. Physical and Flavour Stability of Mayonnaise. Trends Food Sci. Technol. 2001;12:157–163. doi: 10.1016/S0924-2244(01)00079-6. [DOI] [Google Scholar]
  • 140.Raghavan S. Handbook of Spices, Seasonings, and Flavorings. CRC; Boca Raton, FL, USA: 2007. [Google Scholar]
  • 141.El-Abhar H.S., Abdallah D.M., Saleh S. Gastroprotective Activity of Nigella sativa Oil and Its Constituent, Thymoquinone, Against Gastric Mucosal Injury Induced by Ischaemia/Reperfusion in Rats. J. Ethnopharmacol. 2003;84:251–258. doi: 10.1016/S0378-8741(02)00324-0. [DOI] [PubMed] [Google Scholar]
  • 142.Ozdemir N., Kantekin-Erdogan M.N., Tat T., Tekin A. Effect of Black Cumin Oil on the Oxidative Stability and Sensory Characteristics of Mayonnaise. J. Food Sci. Technol. 2018;55:1562–1568. doi: 10.1007/s13197-018-3075-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 143.Ahmad R.S., Imran M., Khan M.K., Ahmad M.H., Arshad M.S., Ateeq H., Rahim M.A. Herbs and Spices-New Processing Technologies. IntechOpen; London, UK: 2021. Introductory Chapter: Herbs and Spices-An Overview. [Google Scholar]
  • 144.Muzolf-Panek M., Kaczmarek A., Tomaszewska-Gras J., Cegielska-Radziejewska R., Szablewski T., Majcher M., Stuper-Szablewska K. A Chemometric Approach to Oxidative Stability and Physicochemical Quality of Raw Ground Chicken Meat Affected by Black Seed and Other Spice Extracts. Antioxidants. 2020;9:903. doi: 10.3390/antiox9090903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 145.Makouie S., Alizadeh M., Khosrowshahi A., Maleki O. Physicochemical, Textural, and Sensory Characteristics of Ice Cream Incorporated with Nigella sativa Seed Oil Microcapsules. J. Food Process. Preserv. 2021;45:e15804. doi: 10.1111/jfpp.15804. [DOI] [Google Scholar]
  • 146.Mahros M.M., Abd-Elghany S.M., Sayed-Ahmed M.Z., Alqahtani S.S., Sallam K.I. Improving the Microbiological Quality, Health Benefits, and Storage Time of Cold-Stored Ground Mutton Supplemented with Black Seed. LWT. 2021;138:110673. doi: 10.1016/j.lwt.2020.110673. [DOI] [Google Scholar]
  • 147.Wojtasik-Kalinowska I., Guzek D., Brodowska M., Godziszewska J., Górska-Horczyczak E., Pogorzelska E., Wierzbicka A. The Effect of Addition of Nigella sativa Oil on the Quality and Shelf Life of Pork Patties. J. Food Process. Preserv. 2017;41:e13294. doi: 10.1111/jfpp.13294. [DOI] [Google Scholar]
  • 148.Anandan S., Keerthiga M., Vijaya S., Asiri A.M., Bogush V., Krasulyaa O. Physicochemical Characterization of Black Seed Oil-Milk Emulsions through Ultrasonication. Ultrason. Sonochem. 2017;38:766–771. doi: 10.1016/j.ultsonch.2016.11.005. [DOI] [PubMed] [Google Scholar]
  • 149.Debonne E., De Leyn I., Verwaeren J., Moens S., Devlieghere F., Eeckhout M., van Bockstaele F. The Influence of Natural Oils of Blackcurrant, Black Cumin Seed, Thyme and Wheat Germ on Dough and Bread Technological and Microbiological Quality. LWT. 2018;93:212–219. doi: 10.1016/j.lwt.2018.03.041. [DOI] [Google Scholar]
  • 150.Pawase P.A., Veer S.J. Utilization of Black Cumin Seed (Nigella sativa) Fractions on Quality Characteristics of Cookies. Int. J. Pharm. Life Sci. 2020;1:16–22. [Google Scholar]
  • 151.Sultan M.T., Butt M.S., Saeed F., Batool R. Nigella sativa Fixed Oil Supplementation Improves Nutritive Quality, Tocopherols and Thymoquinone Contents of Cookies. Br. Food J. 2012;114:966–977. doi: 10.1108/00070701211241563. [DOI] [Google Scholar]
  • 152.Oz E. Inhibitory Effects of Black Cumin on the Formation of Heterocyclic Aromatic Amines in Meatball. PLoS ONE. 2019;14:e0221680. doi: 10.1371/journal.pone.0221680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 153.Okur Ö.D. Determination of Antioxidant Activity and Total Phenolic Contents in Yogurt Added with Black Cumin (Nigella sativa) Honey. Ovidius Univ. Ann. Chem. 2021;32:1–5. doi: 10.2478/auoc-2021-0001. [DOI] [Google Scholar]
  • 154.Abdallah E.M. Black Seed (Nigella sativa) as antimicrobial drug: A mini-review. Nov. Approch. Drug Des. Dev. 2017;3:1–5. [Google Scholar]
  • 155.Yimer E.M. Nigella sativa (Black Cumin): A Promising Natural Remedy for Wide Range of Illnesses. Evid.-Based Complement. Altern. Med. 2019;2019:1528635. doi: 10.1155/2019/1528635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 156.Ahmad F., Ahmad F.A., Ashraf S.A., Saad H.H., Wahab S., Khan M.I., Ali M., Mohan S., Hakeem K.R., Athar T. An updated knowledge of Black seed (Nigella sativa Linn.): Review of phytochemical constituents and pharmacological properties. J. Herb. Med. 2020;25:100404. doi: 10.1016/j.hermed.2020.100404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 157.Bordoni L., Fedeli D., Nasuti C., Maggi F., Papa F., Wabitsch M., de Caterina R., Gabbianelli R. Antioxidant and Anti-Inflammatory Properties of Nigella sativa Oil in Human Pre-Adipocytes. Antioxidants. 2019;8:51. doi: 10.3390/antiox8020051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 158.Sayeed M.S.B., Asaduzzaman M., Morshed H., Hossain M., Kadir M.F., Rahman M. The effect of Nigella sativa Linn. seed on memory, attention and cognition in healthy human volunteers. J. Ethnopharmacol. 2013;148:780–786. doi: 10.1016/j.jep.2013.05.004. [DOI] [PubMed] [Google Scholar]
  • 159.Sedaghat R., Roghani M., Khalili M. Neuroprotective effect of thymoquinone, the Nigella sativa bioactive compound, in 6-hydroxydopamine-induced hemi-parkinsonian rat model. IJPR. 2014;13:227. [PMC free article] [PubMed] [Google Scholar]
  • 160.Kooti W., Hasanzadeh-Noohi Z., Sharafi-Ahvazi N., Asadi-Samani M., Ashtary-Larky D. Phytochemistry, pharmacology, and therapeutic uses of black seed (Nigella sativa) Chin. J. Nat. Med. 2016;14:732–745. doi: 10.1016/S1875-5364(16)30088-7. [DOI] [PubMed] [Google Scholar]
  • 161.Shamim Molla M., Azad A.K., Al Hasib M.A.A., Hossain M.M., Ahammed M.S., Rana S., Islam M.T. A review on antiviral effects of Nigella sativa Pharmacol. Online Newsl. 2019;2:47–53. [Google Scholar]
  • 162.Barakat E.M.F., El Wakeel L.M., Hagag R.S. Effects of Nigella sativa on outcome of hepatitis C in Egypt. World J. Gastroenterol. WJG. 2013;19:2529. doi: 10.3748/wjg.v19.i16.2529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 163.Maideen P., Mohamed N. Miracle Herb to Cure HIV-Black Seeds (Nigella sativa): A Review. Int. J. Med. Rev. 2021;8:116–121. [Google Scholar]
  • 164.Onifade A.A., Jewell A.P., Adedeji W.A. Nigella sativa concoction induced sustained seroreversion in HIV patient. Afr. J. Tradit. Complement. Altern. Med. 2013;10:332–335. doi: 10.4314/ajtcam.v10i5.18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 165.Esharkawy E.R., Almalki F., Hadda T.B. In vitro potential antiviral SARS-CoV-19-activity of natural product thymohydroquinone and dithymoquinone from Nigella sativa. Bioorg. Chem. 2022;120:105587. doi: 10.1016/j.bioorg.2021.105587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 166.Jassey A., Imtiyaz Z., Jassey S., Imtiyaz M., Rasool S. Black Seeds (Nigella sativa) Elsevier; Amsterdam, The Netherlands: 2022. Antiviral effects of black seeds: Effect on COVID-19; pp. 387–404. [Google Scholar]
  • 167.Badary O.A., Hamza M.S., Tikamdas R. Thymoquinone: A Promising Natural Compound with Potential Benefits for COVID-19 Prevention and Cure. Drug. Des. Dev. Ther. 2021;3:1819–1833. doi: 10.2147/DDDT.S308863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 168.Ikhsan M., Hiedayati N., Maeyama K., Nurwidya F. Nigella sativa as an anti-inflammatory agent in asthma. BMC Res. Notes. 2018;11:744. doi: 10.1186/s13104-018-3858-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 169.Alzohairy M.A., Khan A.A., Alsahli M.A., Almatroodi S.A., Rahmani A.H. Protective Effects of Thymoquinone, an Active Compound of Nigella sativa, on Rats with Benzo(a)pyrene-Induced Lung Injury through Regulation of Oxidative Stress and Inflammation. Molecules. 2021;26:3218. doi: 10.3390/molecules26113218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 170.Dajani E.Z., Shahwan T.G., Dajani N.E. Overview of the human investigations of Nigella sativa (Black Seeds): A complementary drug with historical and clinical significance. Gen. Intern. Med. Clin. Innov. 2018;4:2397–5237. doi: 10.15761/GIMCI.1000171. [DOI] [Google Scholar]
  • 171.Dalli M., Azizi S.E., Kandsi F., Gseyra N. Evaluation of the in vitro antioxidant activity of different extracts of Nigella sativa seeds, and the quantification of their bioactive compounds. Mater. Today Proc. 2021;45:7259–7263. doi: 10.1016/j.matpr.2020.12.743. [DOI] [Google Scholar]
  • 172.Block G., Jensen C.D., Norkus E.P., Dalvi T.B., Wong L.G., McManus J.F., Hudes M.L. Usage patterns, health, and nutritional status of long-term multiple dietary supplement users: A cross-sectional study. Nutr. J. 2007;6:30. doi: 10.1186/1475-2891-6-30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 173.Umar Z., Qureshi A.S., Rehan S., Ijaz M., Faisal T., Umar S. Effects of oral administration of black seed (Nigella sativa) oil on histomorphometric dynamics of testes and testosterone profile in rabbits. Pak. J. Pharm. Sci. 2017;30:531–536. [PubMed] [Google Scholar]
  • 174.Ansary J., Giampieri F., Forbes-Hernandez T.Y., Regolo L., Quinzi D., Gracia Villar S., Garcia Villena E., Tutusaus Pifarre K., Alvarez-Suarez J.M., Battino M., et al. Nutritional Value and Preventive Role of Nigella sativa and Its Main Component Thymoquinone in Cancer: An Evidenced-Based Review of Preclinical and Clinical Studies. Molecules. 2021;26:2108. doi: 10.3390/molecules26082108. [DOI] [PMC free article] [PubMed] [Google Scholar]

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Data Availability Statement

The data it is availability within this study.


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