Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Shadma Wahab
 -- 4141 2023-12-13 11:07:03 |
2 Reference format revised.
Lindsay Dong
 Meta information modification 4141 2023-12-19 04:35:58 |

Video Upload Options

We provide professional Video Production Services to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Wahab, S.; Alsayari, A. Pharmacological Activities of Nigella sativa. Encyclopedia. Available online: https://encyclopedia.pub/entry/52680 (accessed on 16 November 2024).
Wahab S, Alsayari A. Pharmacological Activities of Nigella sativa. Encyclopedia. Available at: https://encyclopedia.pub/entry/52680. Accessed November 16, 2024.
Wahab, Shadma, Abdulrhman Alsayari. "Pharmacological Activities of Nigella sativa" Encyclopedia, https://encyclopedia.pub/entry/52680 (accessed November 16, 2024).
Wahab, S., & Alsayari, A. (2023, December 13). Pharmacological Activities of Nigella sativa. In Encyclopedia. https://encyclopedia.pub/entry/52680
Wahab, Shadma and Abdulrhman Alsayari. "Pharmacological Activities of Nigella sativa." Encyclopedia. Web. 13 December, 2023.
Pharmacological Activities of Nigella sativa
Edit
This entry is adapted from the peer-reviewed paper 10.3390/plants12223829

Nigella sativa (NS), also known as black cumin, is one of the plants used in traditional medicine the most. Many studies on the NS have shown that their therapeutic properties are attributed to the seed, oil, and secondary metabolites. This plant has been studied extensively and has many medical uses, such as anti-inflammatory. NS or its phytochemical compounds, such as thymoquinone, can cause cell apoptosis via oxidative stress, block efflux pumps, enhance membrane permeability, and exert potent biocidal effects. 

Nigella sativa phytochemistry bioactive molecules chronic inflammatory diseases thymohydroquinone thymoquinone Anti-Inflammatory

1. Introduction

People have used this plant for over a thousand years as a medicine. Evidence of the oldest cultivation of NS has been discovered by archaeologists, with dating indicating its presence as early as the 2nd century BCE [1]. Nigella is derived from the Latin word Niger, which means “black”. The word “nigellus” denotes a shade of black or dark, explicitly referring to the color of the seed coat. The cultivation of black cumin is seen in several regions throughout Asia, Africa, Europe, and the Americas. NS is growing wild in Turkey, Iraq, Iran, Syria, and Africa [2]. The species is also grown commercially in India [3] and other parts of Southern Asia, Pakistan [4], Iran [5], Western Asia [6], Iraq [6], Israel [7], Jordan [8], Syria [9], Lebanon [10], Turkey [11], Yemen [11], Sudan [12], Northern Africa [12], Egypt [6], Tunisia [6], Ethiopia and Eastern Africa [13]. The primary nations engaged in the production of the commodity are India, Bangladesh, Sri Lanka, Pakistan, Afghanistan, Iraq, Iran, Syria, Ethiopia, and Turkey. Black cumin’s natural average productivity has been reported to be 0.79 tons/ha. In 2018, the black cumin oil market was valued at over 15 million USD; substantial growth is anticipated by 2025 [14]. India cultivates this plant on a large scale due to its heavy consumption in medicine. Annual quantities of black cumin are estimated to be traded in India for more than 100 metric tons. According to Gashaw’s (2020) findings, the average yield in Ethiopia was recorded at 0.64 tons per hectare, a significantly lower figure compared to other nations known for their high agricultural productivity [13]. In 2015, Ermias et al. said the low production was because the cultivars were not very productive [15]. In 2008, Hammo said that it was because the farmers were not using good agronomic practices [16].

In recent years, significant advancements have been achieved in phytochemistry, and health supplements have gained prominence. The medicinal plant is called a chemical manufacturing industry, since it produces a variety of bioactive molecules such as alkaloids, saponins, oleoresins, resins, glycosides, sesquiterpene lactones, and oils [17]. NS’s most abundant chemical components are thymoquinone, α-phellandrene, thymol, proteins, oleic acid, and carbohydrates [18][19]. Previous research has isolated and characterized the primary components of black seeds, including palmitic acid, oleic acid, linoleic acid, and trans-anethole [20]. A study by Kumar et al. found Quiones (thymohydroquinone, thymoquinone, dithymoquinone) and phenolics [21]. Black seed oil was analyzed by Harzallah et al. and yielded 48 unique chemicals, the majority of which were thymoquinone [22]. According to another research, NS seeds contained various chemicals, most of which were monoterpene hydrocarbons. The constituents of NS seed are 0.4–2.5% essential oil, saponin, alkaloids, and 36–38% fixed oils [23]. Unlike most oils, fixed oil contains the unusual fatty acids C20:2arachidic and eicosadienoic [24]. Burits and Bucar et al. analyzed the essential oil using GC-MS. The major components were characterized as thymoquinone (27.8–57.0%), carvacrol (5.8–11.6%), ρ-cymene (7.1–15.5%), trans-anethole (0.25–2.3%), longifoline (1.0–8.0%), and 4-terpineol (2.0–6.6%). Dithymoquinone is easily formed when thymoquinone dimerizes [25]. The chemical structures of some main constituents of Nigella sativa seeds are shown in Figure 3.
Plants 12 03829 g003
Figure 1. Chemical structures of some main constituents of Nigella sativa seeds.

2. Pharmacological Activities of Nigella sativa

2.1. Antioxidant and Anti-Inflammatory

Inflammatory responses are biological processes that protect us from harmful stimuli by coordinating the production of pro- and anti-inflammatory endogenous mediators [26]. NS is a free radical scavenger and improves the action of antioxidant enzymes (glutathione peroxidase, catalase, and glutathione-S-transferase). Thymoquinone’s anti-inflammatory effects were primarily seen in models of inflammation caused by rheumatoid arthritis, colitis, cancer, and asthma [18]. It has been shown to have an anticancer effect via modulating several molecular targets, including p53, p73, STAT3, PTEN, PPAR-g, caspase activation, and reactive oxygen species (ROS) [27]. Nigella sativa seed essential oil was tested for its potential antioxidant properties. An examination was conducted in this study using two TLC screening methods. The results of the study have shown that thymoquinone and the components trans-anethole, carvacrol, and 4-terpineol have antioxidant potential [27].
Regarding managing hyperglycemia and boosting beta cell production in the pancreas, NS is superior to other plant species, thanks to its potent antioxidant and antidiabetic characteristics [28]. Several human clinical studies have produced conflicting findings on the impact of NS on oxidative stress and inflammation indicators. Five different methanolic fractions on guinea pigs were investigated to identify the main constituents of the methanolic extract of NS. All the methanolic fractions had significant relaxant effects, and the 20% fractions from NS were more than that of theophylline at the used concentrations [29]. Nigella sativa seed oil is widely used in the Mediterranean region for its anti-inflammatory properties [30]. Both NS oil and thymoquinone are effective anti-inflammatory agents, reducing the production of inflammatory mediators, including prostaglandins and leukotrienes, in animal models of diseases such as colitis, encephalomyelitis, oedema, peritonitis, and arthritis [31]. At a 4 mL/kg/day dose, NS oil suppressed NO and IL-4 production in rats when given orally for 31 days [32].

2.2. Immunomodulatory Effects of Nigella sativa

Modifying the immune response by controlling communication between its many parts-for example, between neutrophils and macrophages or T and B cells-is known as immunomodulation. Immunomodulators can stimulate or repress the immune system, aiding immunological function [33]. The research on the immunomodulatory properties of NS seed extracts, fixed oil, and essential oils that have been published so far is reviewed [34]. It was investigated in vitro how NS seeds and their soluble fractions affected the reactivity of lymphocytes to various mitogens and the phagocytic activity of polymorphonuclear leukocytes. It was observed that NS stimulates the lymphocyte response to combined allogeneic cells. When cultured with pooled allogeneic cells or without any additional stimulator, NS increased the production of interleukin-3 by human lymphocytes. Interleukin-1 was found to be elevated in response to NS, indicating an influence on macrophages. However, when Staphylococcus aureus was utilized, no impact of NS or its fractions was seen on bacterial phagocytosis or killing, suggesting that the reduction in chemiluminescence activity in the presence of NS is unrelated to the bactericidal activity [35][36]. An increasing body of experimental research indicates that NS and its active components have powerful and positive immunomodulatory effects. NS has been demonstrated to include elements that stimulate T cell-mediated immune responses and inhibit B cell-mediated immunological responses [37][38]. More research is needed to confirm previous findings and uncover novel immunotherapeutic properties of this promising medicinal herb, NS, because few studies have focused on examining NS’s potential immunomodulatory and immunopharmacological effects and its active ingredients.

2.3. Anticancer Activity

The widespread prevalence of cancer makes it a top global health concern [39][40]. We must simultaneously address many global health issues to combat this threat. High death and morbidity rates demonstrate the ineffectiveness of clinical cancer rehabilitation, which includes immunosuppression, chemotherapy, radiation, and surgery. It has increased the need to develop new, more reliable methods of cancer therapy and prevention [41][42][43]. Herbal therapeutics are thus reborn through dietary supplements and botanical preparations. Unique chemical compounds with therapeutic potential are abundant in these medicinal plants [44][45][46][47]. Secondary metabolites are the bioactive substances found in plants and are the building blocks of phytochemicals [48][49][50].
Interestingly, around 60% of anticancer medications have a natural origin [51]. Numerous bioactive compounds have been identified in NS seeds. The seeds comprise fixed and essential oils, alkaloids, saponin, and proteins [52][53]. NS’s critical bioactive component, thymoquinone (TQ), is responsible for the plant’s positive anticancer effect. In-vitro and in-vivo studies have demonstrated that TQ has decisive anticancer and antiproliferative activities against liver, blood, respiratory tract, kidney, colon, and prostate cancers. Combination cancer treatment with NS extract or TQ has been shown to reduce the toxicity of traditional cancer medications, while improving the quality of life for people with advanced cancer [54]. The anticancer activity of (R)-limonene was shown to be mediated by the process of apoptosis and the modification of polyamine metabolism. The compound limonene can trigger apoptosis in LS174T colon cancer cells via a mechanism that involves the mitochondria [55]. Researchers discovered that α-hederin caused a dose- and time-dependent rise in the death of murine leukaemia P388 cells. α-hederin has been shown to exhibit strong antitumor activity in vivo [56]. The efficacy of derivatives derived from TQ-bearing terpene-terminated 6-alkyl residues was evaluated in 518A2 melanoma and HL-60 cells. They discovered that the derivatives cause a slight rise in reactive oxygen species, a drop in mitochondrial membrane potential, and apoptosis linked to DNA laddering [57]. It was discovered that NS extracts, both aqueous and alcohol-based, were successful in vitro in deactivating MCF-7 breast cancer cells [58]. TQ has anti-neoplastic properties and promotes apoptosis in the HCT116 colon cancer cell line [59]. The study conducted by Salim et al. demonstrates the ability of the volatile oil of NS to inhibit colon carcinogenesis in rats at the post-initiation stage, without any observable adverse effects [60]. TQ was potent against the SW-626 colon cancer cells, and the results were similar to 5-fluorouracil in action on HT-29 cells [61]. Chehl et al. also suggested TQ as a new way to stop pro-inflammatory pathways. This idea is promising because it combines ways to control inflammation and help cells die [62]. The anticancer activity of TQ is attributed to potent antioxidant properties in normal cells, and prevents the formation of lipid peroxidation and radicals. TQ acts as a prooxidant, increasing ROS production and causing cancer cells to die after oxidative damage. TQ causes cancer cells to undergo apoptosis by upregulating the transcription factor p53, which promotes apoptosis. Upregulation of the proapoptotic p53 transcription factor is how TQ causes cancer cells to apoptosis. TQ is a cytoprotective molecule that mitigates the harmful effects of chemotherapy on healthy cells without interfering with the therapeutic effects of the drugs themselves in the fight against cancer. It stops cancer cells from dividing and halts the process of angiogenesis [54]. Figure 2. exhibits the possible anticancer mechanism of action of thymoquinone (TQ).
Plants 12 03829 g004
Figure 2. Possible anticancer mechanism of action of thymoquinone (TQ). “+” Means increase and “−” means decrease.

2.4. Antidiabetic Activity

Diabetes is a chronic disease caused by the pancreas’ inability to produce or properly use insulin. Patients with diabetes mellitus often turn to herbal remedies for relief. Dyslipidemia, elevated oxidative stress, and changes in the body’s antioxidant defense system may all be associated with diabetic complications [63]. Worldwide, 451 million people between the ages of 18 and 99 years have diabetes. By 2045, their numbers were predicted to rise to 693 million. Nearly half of all patients with diabetes (49.5%) are thought to remain undiagnosed. In addition, it was predicted that over 21.3 million live births to women were impacted by some hyperglycemia in pregnancy, and it was expected that 374 million individuals had impaired glucose tolerance (IGT). The prevalence of diabetes-related complications was estimated to range from 20 to 90.5% across several studies [64]. Although there is currently no cure for diabetes mellitus, it may be controlled with medications like insulin and dietary changes. Alternative treatment might come from using medicinal herbs [65].
The therapeutic promise is associated with various medicinal plants and their isolated constituents. Diagnosing the antidiabetic characteristics of food items supplemented with medicinal plants often involves measuring the inhibition of α-glucosidase and α-amylase enzymes. The enzyme α-amylase breaks down carbs into simpler disaccharides, while the enzyme α-glucosidase converts the simpler disaccharides into the more easily absorbed glucose [66][67]. This disease can be treated safely and effectively with natural compounds that inhibit these enzymes [68][69]. Diabetes-induced endothelial dysfunction is protected by thymoquinone. Endothelial dysfunction caused by diabetes is mitigated by thymoquinone. Numerous mechanisms are employed to achieve this, including the decrease in inflammatory and apoptotic markers, enhancement of hyperlipidemia, hyperglycemia, and antioxidant function, inhibition of platelet aggregation, and regulation of gene expression related to VCAM-1, eNOS, and LOX-1, which is implicated in endothelial dysfunction. TQ also inhibits the expression and secretion of specific cytokines, including interleukin-1β, MCP-1, NF-κB, TNF-α, and Cox-2, resulting in an anti-inflammatory effect [70]. Patients with type 2 diabetes were given NS seeds as an adjunct treatment to their anti-diabetes drugs [71]. TQ is one of the principal bioactive chemicals shown to have a defensive effect against diabetes, and it is mainly responsible for the therapeutic actions of NS [72]. Figure 3 exhibits the various complications associated with diabetes.
Plants 12 03829 g005
Figure 3. Various complications associated with diabetes.

2.5. Cardiovascular Disease (CVD)

An acute myocardial infarction is consistently ranked as one of the leading causes of death worldwide. Clinical investigators investigated the possible impact of delivering cells to the chemically wounded heart. C-reactive proteins (CRP) are produced in the blood due to inflammation, and their concentration increases as inflammation worsens. Advanced coronary artery inflammation is caused by a pocket of fatty, soft plaque that accumulates and seeps into the arty channel. Rehabilitative methods for the heart include antioxidants, plant life, and physical activity [73]. More people in middle-income nations die from cardiovascular disease than in high-income countries, says the World Health Organization. CVDs are a group of disorders in the heart and blood vessels responsible for the death of approximately 23.6 million people worldwide [74]. People with risk factors like diabetes, high cholesterol, or high blood pressure need more intensive medical and psychological support [75].
One of the most crucial protective factors against CVDs may be eating a diet low in salt, free sugar, and fat, and high in natural plant products [76]. One of NS’s active components, TQ, has been shown to have several biological benefits. Anticancer, antidiabetic, anti-inflammatory, hypolipidemic, and other therapeutic uses of TQ have been established. Flavonoid-rich plants have been utilized for centuries to treat various conditions [77][78]. Due to their antioxidant, anti-inflammatory, and vasodilatory properties, flavonoids are gaining much ground in contemporary pharmacology as a viable therapy for CVDs [79]. TQ contains several bioactive substances [80].
TQ protects against coronary artery diseases, diabetes, hypertension, inflammation, apoptosis, and oxidative stress. TQ’s anti-inflammatory and antioxidant activities may cause its clinical effect against various diseases [81]. TQ’s antioxidant impact is linked to its scavenging ability against reactive oxygen species (ROS), whereas its anti-inflammatory effect is linked to its inhibitory effects on 5-lipoxygenase and cyclooxygenase [82]. TQ also forms glutathione-dihydro-TQ when combined with glutathione (GSH), NADPH, and NADH; this compound is effective against free radicals [83]. It has been noted that TQ has protective properties for treating and inhibiting CVDs [84]. TQ has anti-inflammatory and antioxidant properties, which it uses to combat the many disorders that arise from an imbalance of inflammation and oxidative stress. Although TQ has been found to have cardioprotective benefits in vivo and in vitro settings, the same cannot be said for clinical studies, and more safety evaluations are required to identify the harmful qualities of TQ in people. Additionally, further research is needed to verify its traditional usage as a therapy for cardiovascular disorders. Different mechanisms of actions of Nigella sativa and its phytoconstituents for antioxidant, anti-inflammatory, and antihyperlipidemic effects are shown in Figure 4.
Plants 12 03829 g006
Figure 4. Different mechanisms of Nigella sativa and its phytoconstituents for antioxidant, anti-inflammatory, and antihyperlipidemic effects. The blue arrows indicate decreased effects and red arrows indicate increased effects following NS administration.

2.6. Neurological Disorder

One of the worst outcomes of becoming older is neurodegenerative illnesses, which are caused by damage to the nervous system and abnormal biochemical processes in the body. Neuroprotective and neurotrophic effects are at the forefront of current neuroscience and improve brain health. The elderly are particularly vulnerable to neurodegenerative diseases. Neurological disorders are depression, insomnia, and neurodegenerative diseases; common pathological conditions are neurogenesis impairment, neurotrophic factor deficiency, and oxidative disorder stress. Damage to neurons is exacerbated when microglia and astrocytes are activated in response to oxidative stress, increasing the production of pro-inflammatory mediators. Neuronal injury and degeneration result from producing inflammatory cytokines, creating amyloid plaques and neurofibrillary tangles (NFTs) [73]. Many neurodegenerative diseases have no known cure, and the commercial medications available to treat them all have significant drawbacks. Scientists are thus looking for effective medicines with little adverse effects. Researchers are interested in various phytochemicals because of their potential therapeutic benefits and low risk of negative consequences.
Numerous investigators have elucidated the actions and impacts of NS on the central nervous system. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two examples of neurodegenerative illnesses; NS is known to protect against neurotoxicity and cytotoxicity in such cases [85][86][87]. Amyloid β protein (Aβ) is the main component of neuritic plaques in Alzheimer’s disease (AD), and its accumulation has been considered the molecular driver of Alzheimer’s pathogenesis and progression. Aβ has been the prime target for the development of AD therapy [88]. Additionally, it has been shown that NS seed extracts, both aqueous and methanolic, have sedative solid and depressive effects on the central nervous system; in addition to having analgesic properties, diseases like Alzheimer’s cause gradual brain shrinkage and the buildup of senile plaques in the cortex. Amyloid-beta (Aβ) is a peptide with a molecular weight of 4.2 kD, and there is pathological evidence that it aggregates in the central nervous system [89].
Recent evidence from Elibol et al. demonstrates that micro-osmotic pumps carrying Aβ1-42 may be successfully cannulated into the hippocampus area of adult female rats, where the impact of TQ can then be tested. After eliminating A plaques and restoring neuron viability, the researchers found that TQ (10 and 20 mg/kg) was effective against AD and led to improved memory [90]. TQ was found to be effective against A deposition and its neurotoxicity in human iPSC-derived cholinergic neurons and LPS/IFN-gamma-activated BV2 microglia cells by increasing antioxidant levels and decreasing synaptic plasticity and pro-inflammatory mediators by modulating NF-kappa B (NF-kb)-mediated signaling molecules [91][92]. When injected intraperitoneally at doses of 5 and 10 mg/kg for 4 weeks, TQ was similarly shown to significantly restore memory and learning functioning in male Wistar rats [93]. It has also been shown that NS seeds’ aqueous and methanolic extracts have a potent central nervous system depressant and analgesic effect [94]. The antioxidant and free radical scavenging characteristics of NS, which have been shown to improve memory, are likely attributable to the presence of one or more of its components [95]. It has been demonstrated that NS oil prevents lipid peroxidation in the hippocampus of rats subjected to ischemia-reperfusion damage [96]. S

2.7. Obesity

Several factors have contributed to the alarming rise of obesity in recent decades [97]. The World Obesity Atlas 2022, published by the World Obesity Federation, predicts that one billion people globally, including 1 in 5 women and 1 in 7 men, will be living with obesity by 2030. The findings highlight that countries will not only miss the 2025 WHO target to halt the rise in obesity at 2010 levels, but that the number of people with obesity is on course to double across the globe [98]. Obesity has been linked to an increased risk of many chronic illnesses, including CVDs, atherosclerosis, type 2 diabetes, various forms of cancer, and non-alcoholic fatty liver disease [99]. Reducing caloric intake and increasing exercise are two of the cornerstones of obesity therapy, along with the use of anti-obesity drugs. However, synthetic anti-obesity drugs have adverse side effects, and their effectiveness frequently wanes with continued usage [100]. The public and scientific community have recently shown much interest in plant-based nutrition and medicinal plants as potential alternatives to conventional medicine. Compared to synthetic medications, medicinal plants are easier to get, cheaper, and have fewer adverse side effects [101].
There is ongoing debate about whether NS is effective as an adjunct treatment for weight loss. TQ, which comprises up to 30–48% of NS oil, has been linked to medicinal benefits, including its ability to reduce body fat, which was discovered in recent studies. The pharmacological effects of NS may also be due to other compounds found in the plant, such as thymohydroquinone, thymol, thymoquinone, nigellone and its derivatives; nigellone and its derivatives; nigellone and its derivatives; fatty acids; and flavonoids [102]. The consumption of NS was shown to reduce food intake and enhance energy expenditure in animal models [103][104][105]. In addition, the plant showed no adverse severe or toxicological effects in either human or animal studies [103][106][107][108]. While NS has been shown to help with weight control in certain studies, others have shown little to no benefit [106][109][110][111][112][113][114]. Therefore, the evidence for suggesting NS as a weight-loss supplement is still lacking. Various clinical trials showed that the supplementation with NS exerted moderate effects as a complementary therapy for reducing body weight. No severe side effects were also reported following NS supplementation. Figure 5 shows the chronic problems associated with obesity.
Plants 12 03829 g007
Figure 5. Chronic problems associated with obesity.

2.8. The Influence of NS on Asthma Control

Inflammatory mediators, chronic inflammatory reactions, and oxidative stress play a central role in the pathogenesis of many lung disorders, such as tracheitis, chronic obstructive pulmonary diseases, and asthma [115]. The prevalence of asthma ranges from 1% to 18% worldwide, making it a severe public health concern [116][117]. The symptoms result from a persistent inflammatory process that is mediated and coordinated by the byproducts of specific immune cells [118][119]. However, no effective asthma preventive measures or cures have been discovered, and current treatment focuses on achieving and maintaining clinical control. These strategies may not prevent asthma-related chronic inflammation and remodeling [120][121].
Herbal remedies for asthma in humans and animals have come a long way in recent years [122]. For over 2000 years, NS has been used to treat various illnesses. Research on humans and animals has suggested that NS may have anti-asthmatic properties [53][123][124]. NS has healing and protective properties, such as bronchodilation, reducing inflammation, and protecting against allergies. It also works well at changing the immune system to treat many lung diseases [125][126][127]. It can inhibit histamine receptors, has anti-cholinergic properties, and relaxes various smooth muscle preparations [128][129][130]. In earlier research, NS has been shown to have immunomodulatory, anti-inflammatory, and antioxidant properties [31]. NS has been studied in limited clinical trials for its potential in alleviating asthma symptoms, with results showing substantial improvements in subjective well-being and pulmonary function [131][132][133]. Supplementation with NS for asthmatic patients is not yet supported by enough data to be used routinely in clinical practice. NS supplementation for these individuals has been the subject of numerous recent research, with mixed outcomes [134]. There needs to be more in vivo research showing the effects of NS oil on animals and people [135]. The authors investigated the effects of NS oil in an experimental model of allergic airway inflammation in rats. Oil was injected intraperitoneally before exposing rats to ovalbumin (OVA). The authors examined spleen T cell proliferation and evaluated total IgG1, IgE, and OVA-specific IgG1 blood levels. In addition, they analyzed the expression of genes encoding various cytokines, such as IL-4, IL-5, IL-6, and transforming growth factor-1 (TGF-1). NS oil inhibited inflammatory cell infiltration and pathological lung lesion development, demonstrating its ability to dampen Th2-type responses in rats. NS oil treatment also inhibited T-cell proliferation in the spleen [135]. Balaha and his colleagues studied how giving NS oil to a mouse model of allergic asthma could reduce inflammation and change the immune system. Oral administration of 4 mL/kg/day NS oil dramatically reduced airway responsiveness in OVA-sensitized mice [124].

2.9. Nigella sativa for the Treatment of COVID-19

The first identification of Coronavirus disease-2019 (COVID-19) occurred in China in December 2019. This illness’s causative agent has been Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). SARS-CoV-2 has since disseminated globally, precipitating a substantial epidemic and posing significant obstacles to global healthcare systems [136][137][138]. The majority of individuals inflicted with COVID-19 exhibit either no symptoms or a mild illness that can typically be controlled with the administration of antipyretics, analgesics, hydration, and the application of constitutional symptoms; clinical deterioration is closely monitored [139]. In light of the ongoing epidemic, the quest for a viable therapeutic intervention has emerged as a paramount focus within scientific medical investigation [140].
There are not currently many pharmacotherapeutic medications available that work against COVID-19. Hence, the potential use of complementary herbal medicines, which possess diverse biologically active compounds, is being explored as a therapeutic approach for combating coronavirus infection [41][116][122]. These therapeutic interventions are often used to treat respiratory disorders, and reports have shown their effectiveness in alleviating influenza-related symptoms [141]. Nigella sativa has been recognized as a promising phytomedicine owing to its diverse pharmacological properties, including antiviral, anti-inflammatory, and immunomodulatory actions [142][143]. NS is a well-known cooking spice that has significant health benefits and an extensive history [18][141]. Numerous bioactive constituents have been discovered inside NS, among which thymoquinone is a prominent component [18]. Thymoquinone safety profile has been the subject of multiple clinical studies, one of which involved asthmatic patients and was completed by us [144]. Many preclinical and clinical investigations have provided evidence of NS’s antiviral properties against various viruses [145][146][147][148][149][150][151]. Figure 6 exhibits the different mechanisms of action of Nigella sativa and its secondary metabolites for COVID-19.
Plants 12 03829 g008
Figure 6. Different mechanisms of action of Nigella sativa and its secondary metabolites for COVID-19. NS seeds and its active constituents activate immune cells, make balance between Th1 and Th2 cytokines and initiate antigen presentation system, decreases inflammation, increases anti-inflammation and antihistamine responses. Black cumin bioactive compounds increase autophagy activation by the conversion of LC3II to LC3III, improving comorbidities situation in SARS-CoV-2-infected patients and help in decreasing oxidative stress.

References

  1. Corneanu, C.G.; Corneanu, M. Considerations on Human Evolution and on Species Origin Centers. Oltenia Stud. Comunicări Științele Nat. 2011, 27, 210–217.
  2. Saad, B.; Said, O. Greco-Arab and Islamic Herbal Medicine: Traditional System, Ethics, Safety, Efficacy, and Regulatory Issues; Wiley: Hoboken, NJ, USA, 2011; ISBN 9780470474211.
  3. Ved, D.K.; Goraya, G.S. Demand and Supply of Medicinal Plants in India; NMPB: New Delhi India; FRLHT: Bangalore, India, 2007; pp. 1–18.
  4. Rabbani, M.A.; Ghafoor, A.; Masood, M.S. Narc-Kalonji: An Early Maturing and High Yielding Variety of Nigella sativa Released for Cultivation in Pakistan. Pakistan J. Bot. 2011, 43, 191–195.
  5. Koocheki, A.A. Indigenous Knowledge in Agriculture with Particular Reference to Saffron Production in Iran. Acta Hortic. 2004, 650, 175–182.
  6. Toma, C.C.; Simu, G.M.; Hanganu, D.; Olah, N.; Vata, F.M.G.; Hammami, C.; Hammami, M. Chemical Composition of the Tunisian Nigella sativa. Note II. Profile on Fatty Oil. Farmacia 2013, 61, 454–458.
  7. Botnick, I.; Xue, W.; Bar, E.; Ibdah, M.; Schwartz, A.; Joel, D.M.; Lev, E.; Fait, A.; Lewinsohn, E. Distribution of Primary and Specialized Metabolites in Nigella sativa Seeds, a Spice with Vast Traditional and Historical Uses. Molecules 2012, 17, 10159–10177.
  8. Burdock, G.A. Assessment of Black Cumin (Nigella sativa L.) as a Food Ingredient and Putative Therapeutic Agent. Regul. Toxicol. Pharmacol. 2022, 128, 105088.
  9. Hoppe, B. Handbuch des Arznei-und Gewürzpflanzenbaus; Verein für Arznei-und Gewürzpflanzen Saluplanta: Aschersleben, Germany, 2009.
  10. Paarakh, P.M. Nigella sativa Linn.—A Comprehensive Review. Indian J. Nat. Prod. Resour. 2010, 1, 409–429.
  11. Al-Naqe, G.N.; Ismail, M.M.; Al-Zuba, A.S.; Esa, N.M. Nutrients Composition and Minerals Content of Three Different Samples of Nigella sativa L. Cultivated in Yemen. Asian J. Biol. Sci. 2009, 2, 43–48.
  12. Teuscher, E.; Bauermann, U.; Werner, M.; Brinckmann, J.A.; Lindenmaier, M.P.; Duke, J.A. Book Review: Medicinal Spices: A Handbook of Culinary Herbs, Spices, Spice Mixtures and Their Essential Oils. Food Nutr. Bull. 2006, 27, 271.
  13. Gashaw, Z. Status of Black Cumin (Nigella sativa L.) Research and Production in Ethiopia; A Review. Int. J. For. Hortic. 2020, 6, 20–29.
  14. Kifelew, H.; Fikere, D.; Luleseged, T.; Bekele, D.; Mitiku, H. Wakjira Seed Spices Production Guideline; Ethiopian Institute of Agricultural Research: Addis Ababa, Ethiopia, 2017; pp. 1–36.
  15. Assefa, E. Adaptability Study of Black Cumin (Nigella sativa L.) Varieties in the Mid and High Land Areas of Kaffa Zone, South West Ethiopia. Agric. For. Fish. 2015, 4, 14.
  16. Hammo, Y.H. Effect of Very High Levels of Nitrogen and Phospours Fertilizers, Pinching, and Seed Rate Sowing on Growth, Seed Yield and Componentes of Nigella sativa L. 2—Seed Compenents. Mesopotamia J. Agric. 2008, 36, 2–11.
  17. Yuan, H.; Ma, Q.; Ye, L.; Piao, G. The Traditional Medicine and Modern Medicine from Natural Products. Molecules 2016, 21, 559.
  18. 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.
  19. Cheikh-Rouhou, S.; Besbes, S.; Hentati, B.; Blecker, C.; Deroanne, C.; Attia, H. Nigella sativa L.: Chemical Composition and Physicochemical Characteristics of Lipid Fraction. Food Chem. 2007, 101, 673–681.
  20. Nickavar, B.; Mojab, F.; Javidnia, K.; Roodgar Amoli, M.A. Chemical Composition of the Fixed and Volatile Oils of Nigella sativa L. from Iran. Zeitschrift Naturforsch.-Sect. C J. Biosci. 2003, 58, 629–631.
  21. Venkatachallam, S.K.T.; Pattekhan, H.; Divakar, S.; Kadimi, U.S. Chemical Composition of Nigella sativa L. Seed Extracts Obtained by Supercritical Carbon Dioxide. J. Food Sci. Technol. 2010, 47, 598–605.
  22. Jrah Harzallah, H.; Kouidhi, B.; Flamini, G.; Bakhrouf, A.; Mahjoub, T. Chemical Composition, Antimicrobial Potential against Cariogenic Bacteria and Cytotoxic Activity of Tunisian Nigella sativa Essential Oil and Thymoquinone. Food Chem. 2011, 129, 1469–1474.
  23. Ghedira, K. La Nigelle Cultivée: Nigella sativa L. (Ranunculaceae). Phytotherapie 2006, 4, 220–226.
  24. Houghton, P.J.; Zarka, R.; De Las Heras, B.; Hoult, J.R.S. Fixed Oil of Nigella sativa and Derived Thymoquinone Inhibit Eicosanoid Generation in Leukocytes and Membrane Lipid Peroxidation. Planta Med. 1995, 61, 33–36.
  25. El–Dakhakhny, M. Studies on the Chemical Constitution of Egyptian Nigella sativa L. Seeds. II 1) the Essential Oil. Planta Med. 1963, 11, 465–470.
  26. Nathan, C.; Ding, A. Nonresolving Inflammation. Cell 2010, 140, 871–882.
  27. Burits, M.; Asres, K.; Bucar, F. The Antioxidant Activity of the Essential Oils of Artemisia Afra, Artemisia Abyssinica and Juniperus Procera. Phyther. Res. 2001, 15, 103–108.
  28. Begum, S.; Mannan, A. A Review on Nigella sativa: A Marvel Herb. J. Drug Deliv. Ther. 2020, 10, 213–219.
  29. Keyhanmanesh, R.; Bagban, H.; Nazemiyeh, H.; Bavil, F.M.; Alipour, M.R.; Ahmady, M. The Relaxant Effects of Different Methanolic Fractions of Nigella sativa on Guinea Pig Tracheal Chains. Iran. J. Basic Med. Sci. 2013, 16, 123–128.
  30. 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.
  31. Salem, M.L. Immunomodulatory and Therapeutic Properties of the Nigella sativa L. Seed. Int. Immunopharmacol. 2005, 5, 1749–1770.
  32. Khaldi, T.; Chekchaki, N.; Boumendjel, M.; Taibi, F.; Abdellaoui, M.; Messarah, M.; Boumendjel, A. Ameliorating Effects of Nigella sativa Oil on Aggravation of Inflammation, Oxidative Stress and Cytotoxicity Induced by Smokeless Tobacco Extract in an Allergic Asthma Model in Wistar Rats. Allergol. Immunopathol. 2018, 46, 472–481.
  33. Rizvi, A.; Mahdi, A.A.; Wahab, S.; Mishra, A. Protective Effects of Butea frondosa Leaves against Stress Induced Immune Impairment in Sprague Dawley Rats. Pak. J. Pharm. Sci. 2018, 31, 2457–2462.
  34. Bascones-Martinez, A.; Mattila, R.; Gomez-Font, R.; Meurman, J.H. Immunomodulatory Drugs: Oral and Systemic Adverse Effects. Med. Oral Patol. Oral Cir. Bucal 2014, 19, e24–e31.
  35. Haq, A.; Abdullatif, M.; Lobo, P.I.; Khabar, K.S.A.; Sheth, K.V.; Al-Sedairy, S.T. Nigella sativa: Effect on Human Lymphocytes and Polymorphonuclear Leukocyte Phagocytic Activity. Immunopharmacology 1995, 30, 147–155.
  36. Taifa, S.; Muhee, A.; Bhat, R.A.; Nabi, S.U.I.; Roy, A.; Rather, G.A.; Khan, A.A.; Bashir, S.M.; Patwekar, M.; Wahab, S.; et al. Evaluation of Therapeutic Efficacy of Copper Nanoparticles in Staphylococcus Aureus—Induced Rat Mastitis Model. J. Nanomater. 2022, 2022, 7124114.
  37. Islam, S.N.; Begum, P.; Ahsan, T.; Huque, S.; Ahsan, M. Immunosuppressive and Cytotoxic Properties of Nigella sativa. Phyther. Res. 2004, 18, 395–398.
  38. Swamy, S.M.K.; Tan, B.K.H. Cytotoxic and Immunopotentiating Effects of Ethanolic Extract of Nigella sativa L. Seeds. J. Ethnopharmacol. 2000, 70, 1–7.
  39. Twilley, D.; Rademan, S.; Lall, N. A Review on Traditionally Used South African Medicinal Plants, Their Secondary Metabolites and Their Potential Development into Anticancer Agents. J. Ethnopharmacol. 2020, 261, 113101.
  40. Wahab, S.; Ahmad, I.; Irfan, S.; Baig, M.H.; Farouk, A.-E.; Dong, J.-J. Use of Natural Compounds as a Potential Therapeutic Agent Against COVID-19. Curr. Pharm. Des. 2021, 27, 1144–1152.
  41. Alshehri, S.A.; Wahab, S.; Abullais, S.S.; Das, G.; Hani, U.; Ahmad, W.; Amir, M.; Ahmad, A.; Kandasamy, G.; Vasudevan, R. Pharmacological Efficacy of Tamarix Aphylla: A Comprehensive Review. Plants 2022, 11, 118.
  42. Wahab, S.; Hussain, A. Cytokines as Targets for Immunomodulation. Int. J. Pharm. Pharm. Sci. 2013, 5, 60–64.
  43. Dhanasekaran, S. Phytochemical Characteristics of Aerial Part of Cissus quadrangularis (L) and Its in-Vitro Inhibitory Activity against Leukemic Cells and Antioxidant Properties. Saudi J. Biol. Sci. 2020, 27, 1302–1309.
  44. Jadhav, V.; Bhagare, A.; Wahab, S.; Lokhande, D.; Vaidya, C.; Dhayagude, A.; Khalid, M.; Aher, J.; Mezni, A.; Dutta, M. Green Synthesized Calcium Oxide Nanoparticles (CaO NPs) Using Leaves Aqueous Extract of Moringa Oleifera and Evaluation of Their Antibacterial Activities. J. Nanomater. 2022, 2022, 9047507.
  45. Hani, U.; Osmani, R.A.M.; Yasmin, S.; Gowda, B.H.J.; Ather, H.; Ansari, M.Y.; Siddiqua, A.; Ghazwani, M.; Fatease, A.A.; Alamri, A.H.; et al. Novel Drug Delivery Systems as an Emerging Platform for Stomach Cancer Therapy. Pharmaceutics 2022, 14, 1576.
  46. Shoaib, A.; Tabish, M.; Ali, S.; Arafah, A.; Wahab, S.; Almarshad, F.M.; Rashid, S.; Rehman, M.U. Dietary Phytochemicals in Cancer Signalling Pathways: Role of MiRNA Targeting. Curr. Med. Chem. 2021, 28, 8036–8067.
  47. Akhtar, M.F.; Saleem, A.; Rasul, A.; Faran Ashraf Baig, M.M.; Bin-Jumah, M.; Abdel Daim, M.M. Anticancer Natural Medicines: An Overview of Cell Signaling and Other Targets of Anticancer Phytochemicals. Eur. J. Pharmacol. 2020, 888, 173488.
  48. Palanisamy, N.; Manian, S. Protective Effects of Asparagusracemosus on Oxidative Damage in Isoniazid-Induced Hepatotoxic Rats: An in Vivo Study. Toxicol. Ind. Health 2012, 28, 238–244.
  49. Ahmad, I.; Irfan, S.; Abohashrh, M.; Wahab, S.; Abullais, S.S.; Javali, M.A.; Nisar, N.; Alam, M.M.; Srivastava, S.; Saleem, M.; et al. Inhibitory Effect of Nepeta Deflersiana on Climax Bacterial Community Isolated from the Oral Plaque of Patients with Periodontal Disease. Molecules 2021, 26, 202.
  50. Khalid, M.; Alqarni, M.H.; Alsayari, A.; Foudah, A.I.; Aljarba, T.M.; Mukim, M.; Alamri, M.A.; Abullais, S.S.; Wahab, S. Anti-Diabetic Activity of Bioactive Compound Extracted from Spondias Mangifera Fruit: In-Vitro and Molecular Docking Approaches. Plants 2022, 11, 562.
  51. Juárez, P. Plant-Derived Anticancer Agents: A Promising Treatment for Bone Metastasis. Bonekey Rep. 2014, 3, 599.
  52. Ghosheh, O.A.; Houdi, A.A.; Crooks, P.A. High Performance Liquid Chromatographic Analysis of the Pharmacologically Active Quinones and Related Compounds in the Oil of the Black Seed (Nigella sativa L.). J. Pharm. Biomed. Anal. 1999, 19, 757–762.
  53. Ali, B.H.; Blunden, G. Pharmacological and Toxicological Properties of Nigella sativa. Phyther. Res. 2003, 17, 299–305.
  54. Mehraj, T.; Elkanayati, R.M.; Farooq, I.; Mir, T.M. A Review of Nigella sativa and Its Active Principles as Anticancer Agents. In Black Seeds (Nigella sativa); Elsevier: Amsterdam, The Netherlands, 2022; pp. 91–118.
  55. Jia, S.S.; Xi, G.P.; Zhang, M.; Chen, Y.B.; Lei, B.; Dong, X.S.; Yang, Y.M. Induction of Apoptosis by D-Limonene Is Mediated by Inactivation of Akt in LS174T Human Colon Cancer Cells. Oncol. Rep. 2013, 29, 349–354.
  56. Swamy, S.M.K.; Huat, B.T.K. Intracellular Glutathione Depletion and Reactive Oxygen Species Generation Are Important in α-Hederin-Induced Apoptosis of P388 Cells. Mol. Cell. Biochem. 2003, 245, 127–139.
  57. 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.
  58. Farah, I.O.; Begum, R.A. Effect of Nigella sativa (N. sativa L.) and Oxidative Stress on the Survival Pattern of MCF-7 Breast Cancer Cells. Biomed. Sci. Instrum. 2003, 39, 359–364.
  59. Gali-Muhtasib, H.; Diab-Assaf, M.; Boltze, C.; Al-Hmaira, J.; Hartig, R.; Roessner, A.; Schneider-Stock, R. Thymoquinone Extracted from Black Seed Triggers Apoptotic Cell Death in Human Colorectal Cancer Cells via a P53-Dependent Mechanism. Int. J. Oncol. 2004, 25, 857–866.
  60. Salim, E.I.; Fukushima, S. Chemopreventive Potential of Volatile Oil from Black Cumin (Nigella sativa L.) Seeds against Rat Colon Carcinogenesis. Nutr. Cancer 2003, 45, 195–202.
  61. Rooney, S.; Ryan, M.F. Modes of Action of Alpha-Hederin and Thymoquinone, Active Constituents of Nigella sativa, against HEp-2 Cancer Cells. Anticancer Res. 2005, 25, 4255–4259.
  62. 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.
  63. Association, A.D. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2009, 32, S62–S67.
  64. Kifle, Z.D.; Abdelwuhab, M.; Melak, A.D.; Genet, G.; Meseret, T.; Adugna, M. Pharmacological Evaluation of Medicinal Plants with Antidiabetic Activities in Ethiopia: A Review. Metab. Open 2022, 13, 100174.
  65. Patel, D.K.; Kumar, R.; Laloo, D.; Hemalatha, S. Diabetes Mellitus: An Overview on Its Pharmacological Aspects and Reported Medicinal Plants Having Antidiabetic Activity. Asian Pac. J. Trop. Biomed. 2012, 2, 411–420.
  66. Kumar, J.A.; Tiwari, A.K.; Ali, A.Z.; Madhusudhana, K.; Reddy, B.S.; Ramakrishna, S.; China Raju, B. New Antihyperglycemic, α-Glucosidase Inhibitory, and Cytotoxic Derivatives of Benzimidazoles. J. Enzyme Inhib. Med. Chem. 2010, 25, 80–86.
  67. Ahmad, W.; Amir, M.; Ahmad, A.; Ali, A.; Ali, A.; Wahab, S.; Barkat, H.A.; Ansari, M.A.; Sarafroz, M.; Ahmad, A.; et al. Aegle Marmelos Leaf Extract Phytochemical Analysis, Cytotoxicity, in Vitro Antioxidant and Antidiabetic Activities. Plants 2021, 10, 2573.
  68. Derosa, G.; Maffioli, P. α-Glucosidase Inhibitors and Their Use in Clinical Practice. Arch. Med. Sci. 2012, 8, 899–906.
  69. Asghari, B.; Salehi, P.; Farimani, M.M.; Ebrahimi, S.N. α-Glucosidase Inhibitors from Fruits of Rosa canina L. Rec. Nat. Prod. 2015, 9, 276–283.
  70. Mohebbati, R.; Abbasnezhad, A. Effects of Nigella sativa on Endothelial Dysfunction in Diabetes Mellitus: A Review. J. Ethnopharmacol. 2020, 252, 112585.
  71. Hamdan, A.; Idrus, R.H.; Mokhtar, M.H. Effects of Nigella sativa on Type-2 Diabetes Mellitus: A Systematic Review. Int. J. Environ. Res. Public Health 2019, 16, 4911.
  72. Khader, M.; Eckl, P.M. Thymoquinone: An Emerging Natural Drug with a Wide Range of Medical Applications. Iran. J. Basic Med. Sci. 2014, 17, 950–957.
  73. Alsayari, A.; Wahab, S. Genus Ziziphus for treating Chronic Inflammatory Diseases. Saudi J. Biol. Sci. 2021, 28, 6897–6914.
  74. Ahmad, S.; Beg, Z.H. Elucidation of Mechanisms of Actions of Thymoquinone-Enriched Methanolic and Volatile Oil Extracts from Nigella sativa against Cardiovascular Risk Parameters in Experimental Hyperlipidemia. Lipids Health Dis. 2013, 12, 86.
  75. Chen, L.H. Nutritional Aspects of Aging; CRC Press: Boca Raton, FL, USA, 2018; Volume 1, ISBN 9781351083584.
  76. Stehbens, W.E. An Appraisal of Cholesterol Feeding in Experimental Atherogenesis. Prog. Cardiovasc. Dis. 1986, 29, 107–128.
  77. Farkhondeh, T.; Samarghandian, S.; Azimin-Nezhad, M.; Samini, F. Effect of Chrysin on Nociception in Formalin Test and Serum Levels of Noradrenalin and Corticosterone in Rats. Int. J. Clin. Exp. Med. 2015, 8, 2465–2470.
  78. Samarghandian, S.; Azimi-Nezhad, M.; Borji, A.; Farkhondeh, T. Effect of Crocin on Aged Rat Kidney through Inhibition of Oxidative Stress and Proinflammatory State. Phyther. Res. 2016, 30, 1345–1353.
  79. Samarghandian, S.; Azimini-Nezhad, M.; Farkhondeh, T. The Effects of Zataria Multiflora on Blood Glucose, Lipid Profile and Oxidative Stress Parameters in Adult Mice During Exposure to Bisphenol A. Cardiovasc. Hematol. Disord. Targets 2016, 16, 41–46.
  80. Shafiq, H.; Ahmad, A.; Masud, T.; Kaleem, M. Cardio-Protective and Anti-Cancer Therapeutic Potential of Nigella sativa. Iran. J. Basic Med. Sci. 2014, 17, 967–980.
  81. Mansour, M.A.; Nagi, M.N.; El-Khatib, A.S.; Al-Bekairi, A.M. Effects of Thymoquinone on Antioxidant Enzyme Activities, Lipid Peroxidation and Dt-Diaphorase in Different Tissues of Mice: A Possible Mechanism of Action. Cell Biochem. Funct. 2002, 20, 143–151.
  82. Nagi, M.N.; Mansour, M.A. Protective Effect of Thymoquinone against Doxorubicin-Induced Cardiotoxicity in Rats: A Possible Mechanism of Protection. Pharmacol. Res. 2000, 41, 283–289.
  83. Khalife, K.H.; Lupidi, G. Reduction of Hypervalent States of Myoglobin and Hemoglobin to Their Ferrous Forms by Thymoquinone: The Role of GSH, NADH and NADPH. Biochim. Biophys. Acta-Gen. Subj. 2008, 1780, 627–637.
  84. Liu, H.; Liu, H.Y.; Jiang, Y.N.; Li, N. Protective Effect of Thymoquinone Improves Cardiovascular Function, and Attenuates Oxidative Stress, Inflammation and Apoptosis by Mediating the PI3K/Akt Pathway in Diabetic Rats. Mol. Med. Rep. 2016, 13, 2836–2842.
  85. Beheshti, F.; Hosseini, M.; Vafaee, F.; Shafei, M.N.; Soukhtanloo, M. Feeding of Nigella sativa during Neonatal and Juvenile Growth Improves Learning and Memory of Rats. J. Tradit. Complement. Med. 2016, 6, 146–152.
  86. Cascella, M.; Bimonte, S.; Barbieri, A.; Del Vecchio, V.; Muzio, M.R.; Vitale, A.; Benincasa, G.; Ferriello, A.B.; Azzariti, A.; Arra, C.; et al. Dissecting the Potential Roles of Nigella sativa and Its Constituent Thymoquinone on the Prevention and on the Progression of Alzheimer’s Disease. Front. Aging Neurosci. 2018, 10, 1208–1218.
  87. Khan, M.I.; Ahmad, M.F.; Ahmad, I.; Ashfaq, F.; Wahab, S.; Alsayegh, A.A.; Kumar, S.; Hakeem, K.R. Arsenic Exposure through Dietary Intake and Associated Health Hazards in the Middle East. Nutrients 2022, 14, 2136.
  88. Zhang, Y.; Chen, H.; Li, R.; Sterling, K.; Song, W. Amyloid β-Based Therapy for Alzheimer’s Disease: Challenges, Successes and Future. Signal Transduct. Target. Ther. 2023, 8, 248.
  89. Selkoe, D.J. Alzheimer’s Disease: Genes, Proteins, and Therapy. Physiol. Rev. 2001, 81, 741–766.
  90. Elibol, B.; Beker, M.; Terzioglu-Usak, S.; Dalli, T.; Kilic, U. Thymoquinone Administration Ameliorates Alzheimer’s Disease-like Phenotype by Promoting Cell Survival in the Hippocampus of Amyloid Beta1–42 Infused Rat Model. Phytomedicine 2020, 79, 153324.
  91. Cobourne-Duval, M.K.; Taka, E.; Mendonca, P.; Soliman, K.F.A. Thymoquinone Increases the Expression of Neuroprotective Proteins While Decreasing the Expression of Pro-Inflammatory Cytokines and the Gene Expression NFκB Pathway Signaling Targets in LPS/IFNγ -Activated BV-2 Microglia Cells. J. Neuroimmunol. 2018, 320, 87–97.
  92. Alhibshi, A.H.; Odawara, A.; Suzuki, I. Neuroprotective Efficacy of Thymoquinone against Amyloid Beta-Induced Neurotoxicity in Human Induced Pluripotent Stem Cell-Derived Cholinergic Neurons. Biochem. Biophys. Rep. 2019, 17, 122–126.
  93. Poorgholam, P.; Yaghmaei, P.; Hajebrahimi, Z. Thymoquinone Recovers Learning Function in a Rat Model of Alzheimer’s Disease. Avicenna J. Phytomed. 2018, 8, 188–197.
  94. El-Naggar, T.; Gómez-Serranillos, M.P.; Palomino, O.M.; Arce, C.; Carretero, M.E. Nigella sativa L. Seed Extract Modulates the Neurotransmitter Amino Acids Release in Cultured Neurons in Vitro. J. Biomed. Biotechnol. 2010, 2010, 398312.
  95. Sandhua, K.S.; Cranab, A. Evaluation of Anti Parkinson’S Activity of Nigella sativa (Kalonji) Seeds in Chlorpromazineinduced Experimental Animal Model. Int. J. Pharm. Pharm. Sci. 2013, 5, 884–888.
  96. Hosseinzadeh, H.; Parvardeh, S.; Asl, M.N.; Sadeghnia, H.R.; Ziaee, T. Effect of Thymoquinone and Nigella sativa Seeds Oil on Lipid Peroxidation Level during Global Cerebral Ischemia-Reperfusion Injury in Rat Hippocampus. Phytomedicine 2007, 14, 621–627.
  97. Bray, G.A.; Frühbeck, G.; Ryan, D.H.; Wilding, J.P.H. Management of Obesity. Lancet 2016, 387, 1947–1956.
  98. WOF. One Billion People Globally Estimated to Be Living with Obesity by 2030; World Obesity Federation: London, UK, 2020.
  99. Jung, U.J.; Choi, M.S. Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease. Int. J. Mol. Sci. 2014, 15, 6184–6223.
  100. Kushner, R.F. Weight Loss Strategies for Treatment of Obesity: Lifestyle Management and Pharmacotherapy. Prog. Cardiovasc. Dis. 2018, 61, 246–252.
  101. Hasani-Ranjbar, S.; Nayebi, N.; Larijani, B.; Abdollahi, M. A Systematic Review of the Efficacy and Safety of Herbal Medicines Used in the Treatment of Obesity. World J. Gastroenterol. 2009, 15, 3073–3085.
  102. Daryabeygi-Khotbehsara, R.; Golzarand, M.; Ghaffari, M.P.; Djafarian, K. Nigella sativa Improves Glucose Homeostasis and Serum Lipids in Type 2 Diabetes: A Systematic Review and Meta-Analysis. Complement. Ther. Med. 2017, 35, 6–13.
  103. Zaoui, A.; Cherrah, Y.; Mahassini, N.; Alaoui, K.; Amarouch, H.; Hassar, M. Acute and Chronic Toxicity of Nigella sativa Fixed Oil. Phytomedicine 2002, 9, 69–74.
  104. Le, P.M.; Benhaddou-Andaloussi, A.; Elimadi, A.; Settaf, A.; Cherrah, Y.; Haddad, P.S. The Petroleum Ether Extract of Nigella sativa Exerts Lipid-Lowering and Insulin-Sensitizing Actions in the Rat. J. Ethnopharmacol. 2004, 94, 251–259.
  105. Houcher, Z.; Boudiaf, K.; Benboubetra, M.; Houcher, B. Effects of Methanolic Extract and Commercial Oil of Nigella sativa L. on Blood Glucose and Antioxidant Capacity in Alloxan-Induced Diabetic Rats. Pteridines 2007, 18, 8–18.
  106. Heshmati, J.; Namazi, N.; Memarzadeh, M.R.; Taghizadeh, M.; Kolahdooz, F. Nigella sativa Oil Affects Glucose Metabolism and Lipid Concentrations in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial. Food Res. Int. 2015, 70, 87–93.
  107. Kaplan, S.A.; Meehan, A.G.; Shah, A. The Age Related Decrease in Testosterone Is Significantly Exacerbated in Obese Men With the Metabolic Syndrome. What Are the Implications for the Relatively High Incidence of Erectile Dysfunction Observed in These Men? J. Urol. 2006, 176, 1524–1528.
  108. Meddah, B.; Ducroc, R.; El Abbes Faouzi, M.; Eto, B.; Mahraoui, L.; Benhaddou-Andaloussi, A.; Martineau, L.C.; Cherrah, Y.; Haddad, P.S. Nigella sativa Inhibits Intestinal Glucose Absorption and Improves Glucose Tolerance in Rats. J. Ethnopharmacol. 2009, 121, 419–424.
  109. Hadi, S.; Daryabeygi-Khotbehsara, R.; Mirmiran, P.; McVicar, J.; Hadi, V.; Soleimani, D.; Askari, G. Effect of Nigella sativa Oil Extract on Cardiometabolic Risk Factors in Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Phyther. Res. 2021, 35, 3747–3755.
  110. Badar, A.; Kaatabi, H.; Bamosa, A.; Al-Elq, A.; Abou-Hozaifa, B.; Lebda, F.; Alkhadra, A.; Al-Almaie, S. Effect of Nigella sativa Supplementation over a One-Year Period on Lipid Levels, Blood Pressure and Heart Rate in Type-2 Diabetic Patients Receiving Oral Hypoglycemic Agents: Nonrandomized Clinical Trial. Ann. Saudi Med. 2017, 37, 56–63.
  111. Najmi, A.; Nasiruddin, M.; Khan, R.A.; Haque, S.F. Indigenous Herbal Product Nigella sativa Proved Effective as an Antihypertensive in Metabolic Syndrome. Asian J. Pharm. Clin. Res. 2013, 6, 61–64.
  112. Ibrahim, R.M.; Hamdan, N.S.; Mahmud, R.; Imam, M.U.; Saini, S.M.; Rashid, S.N.A.; Abd Ghafar, S.A.; Latiff, L.A.; Ismail, M. A Randomised Controlled Trial on Hypolipidemic Effects of Nigella sativa Seeds Powder in Menopausal Women. J. Transl. Med. 2014, 12, 82.
  113. Hosseini, M.S.; Mirkarimi, S.A.; Amini, M.; Mohtashami, R.; Kianbakht, S.; Fallah Huseini, H. Effects of Nigella sativa L. Seed Oil in Type II Diabetic Patients: A Randomized, Double-Blind, Placebo—Controlled Clinical Trial. J. Med. Plants 2013, 12, 93–99.
  114. Farzaneh, E.; Nia, F.R.; Mehrtash, M.; Mirmoeini, F.S.; Jalilvand, M. The Effects of 8-Week Nigella sativa Supplementation and Aerobic Training on Lipid Profile and VO2 Max in Sedentary Overweight Females. Int. J. Prev. Med. 2014, 5, 210–216.
  115. Sethi, G.S.; Dharwal, V.; Naura, A.S. Immunological Basis of Oxidative Stress-Induced Lung Inflammation in Asthma and COPD. In Oxidative Stress in Lung Diseases: Volume 1; Springer: Singapore, 2019; Volume 1, pp. 192–223. ISBN 9789811384134.
  116. Wahab, S.; Ahmad, I.; Irfan, S.; Siddiqua, A.; Usmani, S.; Ahmad, M.P. Pharmacological Efficacy and Safety of Glycyrrhiza Glabra in the Treatment of Respiratory Tract Infections. Mini-Rev. Med. Chem. 2021, 22, 1476–1494.
  117. Lambrecht, B.N.; Hammad, H.; Fahy, J.V. The Cytokines of Asthma. Immunity 2019, 50, 975–991.
  118. Boulet, L.P. Airway Remodeling in Asthma: Update on Mechanisms and Therapeutic Approaches. Curr. Opin. Pulm. Med. 2018, 24, 56–62.
  119. Vuolo, F.; Abreu, S.C.; Michels, M.; Xisto, D.G.; Blanco, N.G.; Hallak, J.E.; Zuardi, A.W.; Crippa, J.A.; Reis, C.; Bahl, M.; et al. Cannabidiol Reduces Airway Inflammation and Fibrosis in Experimental Allergic Asthma. Eur. J. Pharmacol. 2019, 843, 251–259.
  120. Chu, E.K.; Drazen, J.M. Asthma One Hundred Years of Treatment and Onward. Am. J. Respir. Crit. Care Med. 2005, 171, 1202–1208.
  121. Ahmad, M.D.F.; Wahab, S.; Ali Ahmad, F.; Intakhab Alam, M.; Ather, H.; Siddiqua, A.; Amir Ashraf, S.; Abu Shaphe, M.; Idreesh Khan, M.; Ali Beg, R. A Novel Perspective Approach to Explore Pros and Cons of Face Mask in Prevention the Spread of SARS-CoV-2 and Other Pathogens. Saudi Pharm. J. 2021, 29, 121–133.
  122. Wahab, S.; Annadurai, S.; Abullais, S.S.; Das, G.; Ahmad, W.; Ahmad, M.F.; Kandasamy, G.; Vasudevan, R.; Ali, M.S.; Amir, M. Glycyrrhiza Glabra (Licorice): A Comprehensive Review on Its Phytochemistry, Biological Activities, Clinical Evidence and Toxicology. Plants 2021, 10, 2751.
  123. Ahmad, M.F.; Ahmad, F.A.; Ashraf, S.A.; Saad, H.H.; Wahab, S.; Khan, M.I.; Ali, M.; Mohan, S.; Hakeem, K.R.; Athar, M.T. An Updated Knowledge of Black Seed (Nigella sativa Linn.): Review of Phytochemical Constituents and Pharmacological Properties. J. Herb. Med. 2021, 25, 100404.
  124. Balaha, M.F.; Tanaka, H.; Yamashita, H.; Abdel Rahman, M.N.; Inagaki, N. Oral Nigella sativa Oil Ameliorates Ovalbumin-Induced Bronchial Asthma in Mice. Int. Immunopharmacol. 2012, 14, 224–231.
  125. Noorbakhsh, M.F.; Shaterzadeh-Yazdi, H.; Hayati, F.; Samarghandian, S.; Farkhondeh, T. Protective Effects of Thymoquinon on Pulmonary Disorders in Experimental Studies. Tanaffos 2018, 17, 211–222.
  126. Saadat, S.; Aslani, M.R.; Ghorani, V.; Keyhanmanesh, R.; Boskabady, M.H. The Effects of Nigella sativa on Respiratory, Allergic and Immunologic Disorders, Evidence from Experimental and Clinical Studies, a Comprehensive and Updated Review. Phyther. Res. 2021, 35, 2968–2996.
  127. Koshak, A.; Koshak, E.; Heinrich, M. Medicinal Benefits of Nigella sativa in Bronchial Asthma: A Literature Review. Saudi Pharm. J. 2017, 25, 1130–1136.
  128. Boskabady, M.H.; Ghasemzadeh Rahbardar, M.; Nemati, H.; Esmaeilzadeh, M. Inhibitory Effect of Crocus sativus (Saffron) on Histamine (H1) Receptors of Guinea Pig Tracheal Chains. Pharmazie 2010, 65, 300–305.
  129. Boskabady, M.H.; Shahabi, M. Bronchodilatory and Anticholinergic Effects of Nigella sativa on Isolated Guinea Pig Tracheal Chains. Iran. J. Med. Sci. 1997, 22, 127–133.
  130. Gilani, A.H.; Aziz, N.; Khurram, I.M.; Chaudhary, K.S.; Iqbal, A. Bronchodilator, Spasmolytic and Calcium Antagonist Activities of Nigella sativa Seeds (Kalonji): A Traditional Herbal Product with Multiple Medicinal Uses. J. Pak. Med. Assoc. 2001, 51, 115–120.
  131. Boskabady, M.H.; Mohsenpoor, N.; Takaloo, L. Antiasthmatic Effect of Nigella sativa in Airways of Asthmatic Patients. Phytomedicine 2010, 17, 707–713.
  132. Boskabady, M.H.; Javan, H.; Sajady, M.; Rakhshandeh, H. The Possible Prophylactic Effect of Nigella sativa Seed Extract in Asthmatic Patients (Fundamental and Clinical Pharmacology (2007) 21, 5, (559–566)). Fundam. Clin. Pharmacol. 2008, 22, 105.
  133. Kalus, U.; Pruss, A.; Bystron, J.; Jurecka, M.; Smekalova, A.; Lichius, J.J.; Kiesewetter, H. Effect of Nigella sativa (Black Seed) on Subjective Feeling in Patients with Allergic Diseases. Phyther. Res. 2003, 17, 1209–1214.
  134. Ciesielska-Figlon, K.; Wojciechowicz, K.; Wardowska, A.; Lisowska, K.A. The Immunomodulatory Effect of Nigella sativa. Antioxidants 2023, 12, 1340.
  135. Shahzad, M.; Yang, X.; Raza Asim, M.B.; Sun, Q.; Han, Y.; Zhang, F.; Cao, Y.; Lu, S. Black Seed Oil Ameliorates Allergic Airway Inflammation by Inhibiting T-Cell Proliferation in Rats. Pulm. Pharmacol. Ther. 2009, 22, 37–43.
  136. Almaghasla, D.; Alsayari, A.; Wahab, S.; Motaal, A.A. Knowledge, Attitudes and Practices with Regard to Prophetic Medicine during the COVID-19 Pandemic in Saudi Arabia. Eur. Rev. Med. Pharmacol. Sci. 2023, 27, 352–358.
  137. Abullais, S.S.; Arora, S.; Wahab, S.; Grover, V.; Alshahrani, M.Y.; Shamsudeen, S.M.; Mohammed Asif, S.; Faragalla, A.I.; Elagib, M.F. Convalescent Plasma Therapy against COVID-19: An Update on the Changing Facets of the Ongoing Pandemic. Curr. Pharm. Biotechnol. 2023, 24, 1515–1523.
  138. Shoaib, S.; Ansari, M.A.; Kandasamy, G.; Vasudevan, R.; Hani, U.; Chauhan, W.; Alhumaidi, M.S.; Altammar, K.A.; Azmi, S.; Ahmad, W.; et al. An Attention towards the Prophylactic and Therapeutic Options of Phytochemicals for SARS-CoV-2: A Molecular Insight. Molecules 2023, 28, 795.
  139. Niknam, Z.; Jafari, A.; Golchin, A.; Danesh Pouya, F.; Nemati, M.; Rezaei-Tavirani, M.; Rasmi, Y. Potential Therapeutic Options for COVID-19: An Update on Current Evidence. Eur. J. Med. Res. 2022, 27, 6.
  140. Vijayvargiya, P.; Esquer Garrigos, Z.; Castillo Almeida, N.E.; Gurram, P.R.; Stevens, R.W.; Razonable, R.R. Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof). Mayo Clin. Proc. 2020, 95, 1454–1466.
  141. Silveira, D.; Prieto-Garcia, J.M.; Boylan, F.; Estrada, O.; Fonseca-Bazzo, Y.M.; Jamal, C.M.; Magalhães, P.O.; Pereira, E.O.; Tomczyk, M.; Heinrich, M. COVID-19: Is There Evidence for the Use of Herbal Medicines as Adjuvant Symptomatic Therapy? Front. Pharmacol. 2020, 11, 1479.
  142. Khazdair, M.R.; Ghafari, S.; Sadeghi, M. Possible Therapeutic Effects of Nigella sativa and Its Thymoquinone on COVID-19. Pharm. Biol. 2021, 59, 696–703.
  143. Shirvani, H.; Rostamkhani, F.; Arabzadeh, E.; Mohammadi, F.; Mohammadi, F. Potential Role of Nigella sativa Supplementation with Physical Activity in Prophylaxis and Treatment of COVID-19: A Contemporary Review. Sport Sci. Health 2021, 17, 849–854.
  144. Koshak, A.; Wei, L.; Koshak, E.; Wali, S.; Alamoudi, O.; Demerdash, A.; Qutub, M.; Pushparaj, P.N.; Heinrich, M. Nigella sativa Supplementation Improves Asthma Control and Biomarkers: A Randomized, Double-Blind, Placebo-Controlled Trial. Phyther. Res. 2017, 31, 403–409.
  145. 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. 2013, 19, 2529–2536.
  146. Onifade, A.A.; Jewell, A.P.; Ajadi, T.A.; Rahamon, S.K.; Ogunrin, O.O. Effectiveness of a Herbal Remedy in Six HIV Patients in Nigeria. J. Herb. Med. 2013, 3, 99–103.
  147. 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.
  148. Salem, M.L.; Hossain, M.S. Protective Effect of Black Seed Oil from Nigella sativa against Murine Cytomegalovirus Infection. Int. J. Immunopharmacol. 2000, 22, 729–740.
  149. Oyero, O.G.; Toyama, M.; Mitsuhiro, N.; Onifade, A.A.; Hidaka, A.; Okamoto, M.; Baba, M. Selective Inhibition of Hepatitis c Virus Replication by Alpha-Zam, a Nigella sativa Seed Formulation. African J. Tradit. Complement. Altern. Med. 2016, 13, 144–148.
  150. Dorra, N.; El-Berrawy, M.; Sallam, S.; Mahmoud, R. Evaluation of Antiviral and Antioxidant Activity of Selected Herbal Extracts. J. High Inst. Public Health 2019, 49, 36–40.
  151. Ulasli, M.; Gurses, S.A.; Bayraktar, R.; Yumrutas, O.; Oztuzcu, S.; Igci, M.; Igci, Y.Z.; Cakmak, E.A.; Arslan, A. The Effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) Extracts on the Replication of Coronavirus and the Expression of TRP Genes Family. Mol. Biol. Rep. 2014, 41, 1703–1711.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Integrative & Complementary Medicine
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Shadma Wahab
,
Abdulrhman Alsayari
View Times: 288
Revisions: 2 times (View History)
Update Date: 19 Dec 2023
Table of Contents
    1000/1000
    Hot Most Recent
    ScholarVision Creations
    Feedback