A Comprehensive Review on Medicinal Importance of Nigella Sativa

Black seed (Nigella sativa) is also referred to as a plant that blooms every year in the Ranunculaceae family. Southeast Asia, the coast of the North Sea area, and western and southern Europe are home to the bulk of black seeds. The black seed is also known as “salvation black kernel” in the word of God, Melanthion by Aristotle and Discroides, and Gith by Paul the Elder [1] (Figure 1). Pakistan generates 40.29million metric tons of refined seed, though the world consumption is 607.3million metric tons [2]. The extract of N. sativa has been indicated to be highly beneficial in the treatment of a range of health conditions, depending on the Unani-Tibb healing system. N. sativa has been historically used in many civilizations throughout the entire globe throughout the beginning of time, and it is known as a “miracle cure” because of its capacity to cure a variety of maladies and regulate the process of self-healing in the human body [3]. In Indian medicine, the seeds serve as a sour, a parasitic agent sharp, pigmentation, stimulant in nature, sporadic high temperature, diuretic medication, paralytic, emmenagogue, stakes, dermatological issues, and indigestion treatment [4,5]. They have suppressive-cancer, xenophobic-diabetic, suppressive-bacterial, known to inhibit-parasitic, suppressive-fungal, and cytotoxic-parasitic properties, as well as therapeutic value. Black seeds are used immediately as a therapeutic compound in traditional medicines or as tea with herbs. Black seed extracts have antioxidant and anti-inflammatory qualities. Patients have used it to treat sneeze dissolving stones in the kidneys, halt the carcinogenic process, relieve stomach discomfort, diarrhea, gas, and polio, and it has choleretic and uricosuric qualities [4,6]. N. sativa is utilized in both conventional and Unani medicinal products in Pakistan. According to previous research, N. sativa is a plant that has great potential for sickness repair as well as well as wellness augmentation; yet additional study will be required to transition botanical therapeutic civilization into fresh medicine systems. Nigellon is a thymoquinone-derived carbonyl polymer. The oil and active components of N. sativa seeds have antiviral, antiseptic in nature blood sugar reducing, cancerpreventing, suppressive-oxidation, neuromuscular relaxing, and inflammatory properties [7-9]. Numerous biological compounds have been historically determined in Nigella sativa species [10]. N. sativa is an annual herbaceous plant in the Ranunculaceae family that is widely farmed in many countries of southern Europe as well as a few locations of Asia, including Saudi Arabia, Pakistan, Syria, India, and Turkey [11]. Its blooms are generally white, pink, yellow, light blue, or lavender in color, with 6-10 petals. The fruit of the plant is a bulky and balloon-like capsule containing numerous black seeds with a bitter and pungent flavor. N. sativa grows throughout November and April each year, and its sprouting phase lasts two weeks following seed sowing. Nevertheless, the berries are typically harvested from vines between January and April [12]. N. sativa seeds have oil, and its medicinal properties were previously used to cool and flavor a variety of meals [13]. N. sativa seeds contain 28-36% fixed oil, which contains a variety of unsaturated fats, such as linolenic, arachidonic, linoleic, and eicosadienoic acids. Myristic, stearic, and palmitic acids are examples of saturated fatty acids [14]. This crude oil has a protective impact, primarily on cells in the brain [15] in the hepatocytes [16]. N. sativa crude oil has just a trace of oil that is volatile and displays functional properties due to thymoquinone, as well as other biological activities. In addition to its modest toxicity, this petroleum product is frequently utilized in nutritional supplements [17] (Figure 2).

Figure 1:Graphical abstract.

Figure 2:A) Nigella sativa seeds B) Nigella sativa plant.

The molecular compound Thymoquinone (TQ) can be identified in black seed vital oil and has been believed to be vital for many of the seed’s therapeutic effects [18]. TQ is recognized for its capacity to inhibit the degradation of lipids and neutralize free radicals. Similarly, combination of TQ with ifosfamide raises the indication of treatment effectiveness and protects non-malignant tissues from the harm induced by chemotherapy [19]. Investigators encountered the therapeutic effects of TQ in safeguarding the wellness of humans and combating malignancy using biological sequence alteration. As a result, compounds which prompt carcinoma cells to die may lead to successful therapies for cancer in the future [20]. TQ has been proven to be efficacious across a wide range of multidrug-resistant human cancer cells and to aid in the suppression and stimulation of necrosis in cancer cells. The research investigation showed that TQ could potentially be administered as a nutritional product to enhance the potency of other anti-cancer drugs. A clinical trial integrating TQ with anti-cancer drugs might reduce side effects and increase therapeutic efficacy [19]. N. sativa has an array of other active compounds that help to prevent neoplasia in addition to thymoquinone. Alkaloids, also peptides, essential as well as vital fats, and tannin are a few categories. Previous study determined the precise mechanism whereby N. sativa volatile crude oil blocks development of cancer [21]. One plausible explanation of TQ’s chemo preventive effects, anti-inflammatory and antioxidant qualities as well as its elimination technologies improvement [19].

Pancreatic cancer

TQ from N. sativa oil extract promoted apoptosis and reduced the proliferation of PDA (Pancreatic Ductal Adenocarcinoma) cells, as demonstrated [22]. It was previously shown to have cancer prevention activities among human hepatic cancer, endometrial a cancerous tumor, Edwards’s peritoneal tumors, and the work of Dalton diarrhea, leukemia or with typical lymphocytes illustrating barely any mortality [18].

Hepatic cancer

It is discovered that swallowing TQ greatly improved the purpose of Quinone aminotransferase and cysteine transferase, presenting a possible preventive approach for the development of tumors and severity in liver carcinoma [23].

Cervical cancer

Based on infections with HPV are the underlying an etiology of all carcinogenic malignancies, with varieties of HPV 16 and 18 contributing to around 70% of all genital cinomas. TQ drastically decreases the lifespan of Siha cells, C33A, and several HPV-positive lineages of cells [24].

Numerous studies have linked the antioxidant value of N. sativa to its fascist-allergic and immunomodulatory actions. Multiple studies inquiries have revealed that unstable oxygen radicals have a role in immunological and antimicrobial properties [25].

Nutritional deterioration is caused by the formation of Reactive Oxygen Species (ROS), who additionally alter the structure and activity of biomolecules such as DNA, dietary fiber, peptides, and fatty substances [26]. In contradiction to preventative defensive mechanisms which include the enzyme catalase gsh-s-transferase (GST), the enzyme super oxide dismutase, glucose peroxidase, and superoxide dismutase (GPx), oxidative damage results in the synthesis of a large number of reactive oxygen species. Antivirus protecting the functioning of cells from the harmful impacts of volatile oxygen as well as nitrogen oxides. Antibodies perform an integral part as ROS investigators. It can be synthesized alternatively locally or intentionally by cells. The antioxidant abilities of N. sativa essence are owed to the presence of chemical compounds that include carvacrol in sulfuric acid, and several [27]. Further, TQ and black seed enhanced diets enhance simultaneously physiological (SOD, CAT, GPX, and GST) and free of enzymes (GSH and ascorbic acid) antioxidant capacities. Medication with N. sativa elevated haemoglobin concentrations in red blood cells besides possessing an adequate anti-oxidative armour towards reactive nitrogen species and oxygen and hampering neutrophil proliferation in the brain and spinal cord [28]. Superoxide, peroxide from hydrogen, and numerous other exceptionally reactive molecules made up of nitrogen are inhibited by N. sativa [29]. The breakdown of parts of the matrix by physiological reactive oxygen species via activation of latent collagen enzymes has been scientifically associated to articular Radicals and rheumatism [30]. Malondialdehyde and the Thiobarbituric Acid Responding Material (TBARS) are oxidative lipid crayons. Multipurpose oxidation of fatty acids develops throughout an assortment of cascade processes that ultimately result in barrier rupture. The robust antioxidant qualities of N. sativa mitigated ROS emergence, which in turn diminished the breakdown of lipids [31,32]. Moreover, N. sativa suppressed MDA levels in the mouse brain’s activity, lymph nodes, liver, and serum in the blood [33,34,28].

Difficulty in breathing, an ongoing aggressive ailment of the bronchial arrangement, are triggered by an accumulation of periodically adjusting inflammatory mediators, cells that are inflammatory (mast tissue cells, plasma cell lymphocytes, etc.), and overproduction of mucus formation. According to worldwide asthmatic estimations, over 300 million people worldwide are affected, with more than 100 million at risk by the conclusion of 2025 [35]. Asthma affects people of every generation. Glucocorticosteroids are often prescribed for treating respiratory conditions, disregarding being aware that they have unidentified negative consequences such as deficient bone metabolism, slower expansion, and pituitary protection [36]. In addition, some with allergies reacted harshly or significantly to medication with steroids [37]. As an outcome, initiatives are underway towards creating specific, secure and suppressive-asthmatic pharmaceuticals that utilize naturally occurring substances. In accordance with study, certain naturally appearing seed varieties, especially the famous N. sativa, have a substantial impact on decreasing the seriousness of bronchitis [38,39]. Asthma is triggered by an assortment of cell connections, inflammatory disorders, completely imperviousboosting drugs, and other factors. Cells in the mast dendritic cells, with the goal of T helper cells (especially Th1, Th2, and Th9 cells), B cells, lymphocytes, lymphoid stem cells eosinophils, and neutrophils basophils, phagocytes, and epithelial cells constituted the key immune cells that were associated with lung disease-related irritation [38,39]. They also have an importance in the fundamental reasons of respiratory and lung damage in the emergence of asthma. Actually, the cells contribute considerably to the onset of severe asthmatic bronchitis by releasing cytokines [40,41]. The study’s findings supported the notion that cytokine multiplication is the main mediator of the activity during inflammation. The primary cytokines generating influenza have been determined as pro-inflammatory mediators manufactured by the cells, such as IL- 4, IL-5, and IL-13, as well as IFN- and IL-6 (cytokines emitted by Th1 cells) [42,43]. Unexpectedly, each person’s blood has a high level of fall dramatically, that contributed to the documented recovery. It’s important to remember because [44] additionally described a double-blind study standardized investigation which includes individuals with asthma, which revealed a transient pulmonary effect after receiving just a single dosage of N. sativa (50mg/kg) [44].

Effect of black seed (N. sativa) on immunomodulation

Nigella sativa is a plant that has played an important part in immune response strengthening and ailments therapies, especially irritation of the skin, autoimmune diseases, allergic rhinitis, thyroiditis caused by Hashimoto’s, and others. Drug sensitivity and leftover immunomodulatory agents such as lenalidomide, antibiotics, pomalidomide, thalidomide have become prevalent when administered combat infectious agents. On the contrary, herbal medicine may be favorable than conventional medicinal products. N. sativa kernels and their purified biologically active elements are frequently utilized to treat and prevent a wide range of illnesses related to the immune system. N. sativa exhibits the ability to boost cellular immunity via T lymphocytes, which are associated with immune response [45]. In a Streptozotocininduced diabetes with a type 1 diagnosis rat framework, the oil extracted from N. sativa minimized the concentration of militantislet cell immune system antibodies as well as the main antibody molecules produced in the autoimmune conditions procedure, resulting in a substantial decrease in the amount of immunological barriers indications Pan B-lymphocytes (CD19), Pan innate cells (CD 1 lb), and Pan T-lymphocytes (CD90). According to Hmza AJ et al. [46] N. sativa oil stimulates elderly immunologic sensitivity and T responder cell generation [47]. In a mouse model, N. sativa significantly raised the total (leukocyte) frequency and the amount of hemoglobin generated by doxorubicin while also increasing T-lymphocyte cell development. A study realised that the extract of N. sativa decreases the number of militant-islet cell immunoglobulins which are also the main antigens produced in the autoimmune illnesses manipulate, and leads to an impressive decrease of immune-mediated indications Pan B-lymphocytes (CD19), Pan innate cells (CD 1 lb), and Pan T-lymphocytes (CD90) in a Streptozotocin-induced diabetic rat framework [46]. It is observed that N. sativa oil enhances ageing immunologic protection and T lymphocyte cell generation [47]. In an animal study, N. sativa significantly boosted the total (leukocyte) frequency and haemoglobin concentrations caused by cisplatin, while likewise boosting T-lymphocyte cell development [48,49]. This is comparable to a research investigation that discovered N. sativa promotes total erythrocyte and anemia content in an irinotecan-induced mice model. Therefore, the mentioned seed boosted T-lymphocyte cells (cluster of differentiation 3), helper T-lymphocyte cells (cluster of differentiation 4), and repressor to harmful T lymphocyte cells (cluster of differentiation 8) [50]. It is concluded that individuals that acquired hypersensitivity reaction-specific immunotherapy, which is in conjunction with N. sativa (2g/day) utilization along with vaccinations made more improvements (polymorph-nuclear erythrocyte acts (PMNs) and group of proliferation 8 (CD8 counts) than individuals to which obtained solely the immune system for the duration of two months. He concluded that treatment with N. sativa gave rise to greater efficacy chemotherapy [51].

Antibiotics serve as the backbone for medical practice throughout the latter half of the 20^th century, sparing numerous individuals from major bacterial infections. Nevertheless, during the late twentieth and early twenty-first century, antimicrobial resistance in harmful microbes slowly started to emerge internationally [52,53]. The growing fear of pathogenic infections and antibiotic-resistant microbes needs a worldwide search for imaginative therapies that may be centered on natural commodities including vegetation whose are selected depending on well-known ethnomedicinal usage. Black cumin is one of the most inspiring therapeutic plants, with antiviral, antibacterial, antifungal, and antiparasitic qualities [54,55].

In besides hindering lactic acid biofilm formation, thalidomide obtained from N. sativa seeds revealed wider spectrum endeavors contrary to a variety of bacterial genera, which includes Pseudomonas, Escherichia Bacillus, Enterococcus, Staphylococcus, Pseudomonas, Listeria, Serovar, and Vibrio parahaemolyticus and Micrococcus [56]. The dimethyl alcohol obtained from the inside of the seed significantly reduced larger gram-positive microorganisms (S. pyogenes) versus gram-negative bacteria (P. aeruginosa, bacteria such as K. pneumoniae, and P. vulgaris) [57]. Different quantities for N. sativa hydrocarbons (100%, 80%, 50%, 40%, 30%, and 20%) prevented each of the microbial isolates investigated towards products which are produced-resistant S. aureus isolates [58]. Thymoquinone displayed significant bactericidal properties towards gram-negative bacteria, exhibiting MICs spanning 8 to 32g/ mL, and creating the cheapest inhibitors of biofilm concentrations both S. aureus and S. epidermidis, at 22 and 60g/mL, accordingly [59]. Additionally, black seed (2g/day) demonstrated a known effectiveness to inhibit H. pylori effect equivalent to triple medical care. This establishes an excellent basis for additional investigation into the potential uses of this unique seed for the treatment of H. latent infection-induced ulcers in the stool [60].

It was recently proven that the vital oil of N. sativa with various origins has considerable protective properties towards pathogenic bacteria, dermatological fungi and non dermatophytic filamentous fungal organisms, along with mycotoxins-producing microorganisms. The N. sativa treatments addressed the cell’s inner wall, the membrane of the plasma cell, and membranous organelles that are present especially in the nucleus and mitochondria, considering the physical appearance of these toxigenic fungi [61]. Besides, black cumin and TQ extracts show substantial fungicidal action contrary to dermatophyte isolates which include Trichophyton mentagrophytes and Microsporum gypseum, being superior to fluconazole but not as effective as ketoconazole [62].

When contrasted with Amphotericin-B, Thymoquinone hindered the proliferation of Fusarium olani and Aspergillus niger or was beneficial regarding the colonies of Candida albicans, yeast tropicalis, and Candida krusei [63,64] researched the constituents of Nigella sativa such as thymo, TQ, and thymo hydro-quinone and discovered that the ingredient of black cumin exhibited antifungal activity against yeast, dermatophytes, and molds. N. sativa has antimicrobial properties and can help preserve food from spoiling (Table 1) [65-71].

Table 1:Some traditional uses of Nigella sativa seeds.

The mechanisms by which N. sativa seeds and their contents exert their therapeutic benefits must be studied in more detail. Future research on the molecular structure of TQ, alpha-hederin, and other components of N. sativa seeds may result in the development of more potent and secure medications for the treatment of a wide range of ailments. For a successful treatment of numerous infectious illnesses and to circumvent the resistance issue, N. sativa seeds, its oil, and components such as TQ, alphahederin, or others might be utilised in appropriate combinations with currently available chemotherapeutic drugs. Additionally, additional studies should concentrate on and investigate the precise cellular and molecular targets of numerous N. sativa components, including TQ. This review article is dedicated to all researchers interested in concentrating their research on this wonder plant. It is our hope that this review article will assist researchers in their investigation and further preclinical and clinical studies on the use of N. sativa for the treatment of a variety of diseases.

Nigella sativa is a versatile plant with a wide range of potential health benefits. Its seeds are rich in Thymoquinone (TQ), a molecular compound with potent antioxidant and anti-inflammatory properties. Research has shown that TQ has the potential to prevent tumor development and reduce the proliferation of cancer cells. Additionally, N. sativa has been found to strengthen immune response, combat pathogenic bacteria and fungi, and lower blood pressure and cholesterol levels. Its potential therapeutic uses include the treatment of skin inflammation, autoimmune diseases, and Hashimoto’s thyroiditis. N. sativa is also commonly used as a seasoning in various food preparations. However, further research is needed to fully understand the plant’s medicinal properties and potential side effects. Nigella sativa, also known as black seed, is an annual herbaceous plant that is widely cultivated in many countries of southern Europe and Asia. Its fruit contains numerous black seeds that are rich in thymoquinone (TQ), a molecular compound that has been linked to many of the seed’s therapeutic effects. N. sativa has been shown to be highly beneficial in the treatment of a range of health conditions and has been referred to as a “miracle cure.” The plant possesses immunological and antimicrobial properties and has been proven to inhibit the growth of pathogenic bacteria, dermatological fungi, and non-dermatophytic filamentous fungal organisms. N. sativa is also used as a flavouring ingredient and seasoning in various food preparations. It has been shown to lower blood pressure, reduce cholesterol levels, and improve glucose balance, making it an effective therapeutic agent for diabetes management. Furthermore, studies have indicated that N. sativa extract could potentially be a preventive approach for the development of tumors and severity in liver carcinoma. In vitro studies have also demonstrated that N. sativa extract could decrease the electrogenic gastrointestinal absorption of glucose. Overall, N. sativa is a promising therapeutic plant with a wide range of potential health benefits.

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