Therapeutic and Pharmaceutical Potential of Nigella sativa and its Bioactive Constituents in Chronic Inflammatory Diseases: Progress, Challenges, and Future Perspectives

Studies on black cumin genotypes of Turkiye: Agronomy, seed and thymoquinone yields

Optimization of yield and thymoquinone content of screw press-extracted black cumin seed oil using response surface methodology

Black cumin (Nigella sativa L.) seeds essential oil compositions (EOCs) have been used for their medicinal and aromatic values across the world since ancient times. Studies have revealed the presence of variability among black cumin genotypes in EOCs. In Ethiopia, few studies have been conducted to explore the variability of black cumin genotypes by using EOCs. This study investigated the variability of Ethiopian black cumin genotypes (EBCGs) by EOCs. Seeds of 64 N. sativa genotypes were used for this experiment. Composite samples of 100 g of seeds were collected and roughly ground from each genotype. The extraction was made by hydrodistillation using a Clevenger-type apparatus for 3 h, and the essential oil was collected by measuring the amount using a measuring pipette. The essential oil samples were stored in a refrigerator at 4°C until gas chromatography-mass spectrometry (GC-MS) analysis. Descriptive statistics was used to estimate the variations among populations' combined mean values of EOCs using the SAS version 9.4 software package. The correlation and hierarchical clustering analysis were made based on the combined mean values of EOCs using the R-software version 4.2.2 packages. A total of 21 EOCs were detected from the essential oil of 64 EBCGs using GC-MS, out of which ρ-cymene, thymoquinone, α-thujene, carvacrol, trans-4-methoxythujane, longifolene, terpinen-4-ol, β-pinene, α-pinene, and d-limonene dominated the essential oils. Among these, ρ-cymene, thymoquinone, α-thujene, trans-4-methoxythujane, and carvacrol were the most abundant constituents in all genotypes, while the rest varied among the genotypes. It is predicted that the major EOCs will be improved by 25.33%-152.14% over improved varieties by selecting the top 5% of landraces. The abundant EOC thymoquinone had a significant and positive correlation with carvacrol and a strong and significant negative correlation with α-thujene, α-pinene, β-pinene, ρ-cymene, and d-limonene. Based on the major EOCs, cluster analysis grouped the 64 genotypes into two different chemotypes. Cluster-I: Chemotype A is characterized by a high content of thymoquinone. Cluster-II: Chemotype B is characterized by a high content of ρ-cymene. The presence of the most abundant volatile constituents in genotypes 242835, 9068, and 014_ATH means they are essential for the pharmaceutical and food industries. This study disclosed the existence of a significant diversity of EOCs among the Ethiopian N. sativa genotypes, which can be exploited for future improvement programs.

Black cumin seeds (Nigella sativa) and black cumin seed oil (BCSO) exhibit various pharmacological activities, most of which are attributed to the presence of thymoquinone (TQ). TQ, however, is characterized by low stability at elevated temperatures and instability in aqueous environments. In this study, the spectroscopic properties of TQ were used to monitor changes in TQ content in BCSO subjected to thermal exposure. Simultaneously, the influence of the presence of TQ on the antioxidant properties of this oil was determined. The used spectrofluorimetric and chromatographic method quantified the presence of TQ. The antiradical properties of the oil in different stages of thermal oxidation degradation were determined by the DPPH method. The measured antiradical activity of the oil, depending on the exposure conditions used, revealed the difference correlated with the content of the TQ. However, the presence in BCSO of other bioactive components, like phenols, had a more significant influence on its total antioxidant capacity. Furthermore, our study, for the first time, focused on the rise in TQ content in the oil during thermal storage, indicating a new method to enhance the TQ content in BCSO.

Nigella sativa, commonly known as black cumin, is widely recognized for its medicinal properties, including its antihyperuricemic, antioxidant, and anti-inflammatory effects. This study aimed to evaluate and compare the antihyperuricemic potential of three varieties of Nigella sativa seeds from Bangladesh, Syria, and Turkey, as well as their phytochemical composition. Using Gas Chromatography-Mass Spectrometry (GC-MS), key bioactive compounds, such as thymoquinone, p-cymene, and α-phellandrene, were identified and quantified. An animal model of hyperuricemia was established in Sprague-Dawley rats using a fructose-brewer’s yeast diet, and therapeutic effects were assessed by administering standardized doses of Nigella sativa and comparing their efficacy to allopurinol, a conventional gout medication.The results revealed significant phytochemical variability among the three origins, with Turkish Nigella sativa exhibiting the highest levels of thymoquinone and p-cymene, while the Syrian variety showed unique bioactivity despite lower thymoquinone content. Statistical analysis demonstrated that all three seed varieties effectively reduced uric acid levels, with Turkish Nigella sativa producing the most significant reduction. In silico predictions using pkCSM , SuperPred and Pro Tox III provided insights into mechanisms of action and pharmacokinetics and their toxcity, highlighting the potential of Nigella sativa as a complementary treatment for hyperuricemia and gout. This research emphasizes the importance of geographical influence on the medicinal properties of Nigella sativa and contributes to the understanding of its pharmacological applications.

Nigella sativa L. (black cumin) is an annual herb of the Ranunculaceae family, traditionally used in Middle Eastern and Asian medicine for the management of various health conditions. Its seeds and oils are rich in bioactive compounds, including alkaloids, essential fatty acids, nigellone, saponins, and thymoquinone (TQ), which contribute to diverse pharmacological activities such as anticancer, antidiabetic, anti-inflammatory, antimicrobial, antioxidant and hepatoprotective effects. In the present study, oils obtained from Turkish and Syrian N. sativa seeds through cold pressing were investigated. Phytochemical composition was characterized using Gas Chromatography (GC) and High Performance Liquid Chromatography (HPLC), with particular focus on fatty acid profiles and TQ content. Additionally, tyrosinase inhibitory activities of the fixed oils and TQ were evaluated. It was noted that variations in the composition of seed samples originating from different countries influence the phytochemical features of the plant materials. Accordingly, maintaining genetic diversity and implementing appropriate cultivation strategies are essential for the sustainability of agricultural production.

Identification and functional characterization of a γ-terpinene synthase in Nigella sativa L (black cumin)

SUMMARYResearch backgroundNigella sativa L., commonly known as black cumin, is a medicinal plant renowned for its rich bioactive composition and health-promoting properties. Among its key compounds, thymoquinone has gained significant attention in nutraceutical and pharmaceutical research for its potential to prevent and manage chronic inflammatory conditions and immune dysfunctions. With growing global interest in natural health solutions, the aim of this study is to optimise ultrasound-assisted extraction (UAE) conditions to maximise thymoquinone yield from the extract of black cumin (Nigella sativa L.) seeds and characterise the bioactive compounds. By using UAE and advanced analytical techniques, the research contributes to the development of sustainable extracts rich in bioactive compounds with applications in medicine and nutrition.Experimental approachIn this study, ultrasound-assisted extraction method was used with response surface methodology (RSM) software to extract the bioactive compounds, including total phenolic content (TPC) and compounds that can bind free DPPH radical. To increase the extraction efficiency of bioactive compounds, the following parameters were examined: the ratio of the mass of seed powder to the volume of solvent of 50–100 %, extraction temperature of 30 °C, amplitude of 30–60 % and extraction time of 30–60 min. Black cumin seed extracts were characterised using scanning electron microscopy (SEM), while gas chromatography-mass spectrometry (GC-MS) analysis was carried out to identify thymoquinone. Additionally, Fourier transform infrared (FTIR) spectroscopy confirmed the presence of thymoquinone and several functional groups, including amines, alkanes, acids, esters, alkyls and alkenes.Results and conclusionsUltrasonic extraction using methanol as a solvent resulted in a higher yield of thymoquinone (28.62 %), identified using GC-MS analysis. The presence of thymoquinone was further confirmed by the functional groups detected in FTIR analysis. Under the specified extraction conditions, total phenolic content (TPC, expressed as gallic acid equivalents), yield (in %) and DPPH radical scavenging activity increased by approx. 271.03 mg/g, and 4.5 and 83.06 %, respectively. In addition to thymoquinone, thymohydroquinone was also identified based on its molecular mass, retention time and peak values. Thymoquinone, a natural and potent phytochemical, offers a range of therapeutic properties, including immune-enhancing potential.Novelty and scientific contributionThymoquinone is a bioactive compound found in black cumin seeds, known for its potent antioxidant and immunity boosting properties. This research was conducted achieve the best possible extraction conditions for bioactive substances. Additionally, the results support the potential of thymoquinone as a therapeutic agent to treat various health conditions. The novelty lies in the development and optimisation of extraction techniques to maximise the yield and bioactivity of thymoquinone, a compound renowned for its robust antioxidant and immune-modulating properties. This work uniquely bridges the gap between the traditional use of black cumin and modern scientific validation, and addresses global health priorities. The results emphasise the importance of Nigella sativa as a sustainable and natural source of health-promoting compounds, meeting the increasing demand for plant-based bioactive compounds in preventive healthcare. By characterising the extraction conditions and demonstrating therapeutic potential of thymoquinone, this study contributes to both the scientific literature and practical advances in the development of functional food and nutraceuticals.

The prevalence of chronic kidney disease (CKD) is increasing worldwide, and a close association between acute kidney injury (AKI) and CKD has recently been identified. Black cumin (Nigella sativa) has been shown to be effective in treating various kidney diseases. Accumulating evidence shows that black cumin and its vital compound, thymoquinone (TQ), can protect against kidney injury caused by various xenobiotics, namely chemotherapeutic agents, heavy metals, pesticides, and other environmental chemicals. Black cumin can also protect the kidneys from ischemic shock. The mechanisms underlying the kidney protective potential of black cumin and TQ include antioxidation, anti-inflammation, anti-apoptosis, and antifibrosis which are manifested in their regulatory role in the antioxidant defense system, NF-κB signaling, caspase pathways, and TGF-β signaling. In clinical trials, black seed oil was shown to normalize blood and urine parameters and improve disease outcomes in advanced CKD patients. While black cumin and its products have shown promising kidney protective effects, information on nanoparticle-guided targeted delivery into kidney is still lacking. Moreover, the clinical evidence on this natural product is not sufficient to recommend it to CKD patients. This review provides insightful information on the pharmacological benefits of black cumin and TQ against kidney damage.

Mounting evidence support the potential benefits of functional foods or nutraceuticals for human health and diseases. Black cumin (Nigella sativa L.), a highly valued nutraceutical herb with a wide array of health benefits, has attracted growing interest from health-conscious individuals, the scientific community, and pharmaceutical industries. The pleiotropic pharmacological effects of black cumin, and its main bioactive component thymoquinone (TQ), have been manifested by their ability to attenuate oxidative stress and inflammation, and to promote immunity, cell survival, and energy metabolism, which underlie diverse health benefits, including protection against metabolic, cardiovascular, digestive, hepatic, renal, respiratory, reproductive, and neurological disorders, cancer, and so on. Furthermore, black cumin acts as an antidote, mitigating various toxicities and drug-induced side effects. Despite significant advances in pharmacological benefits, this miracle herb and its active components are still far from their clinical application. This review begins with highlighting the research trends in black cumin and revisiting phytochemical profiles. Subsequently, pharmacological attributes and health benefits of black cumin and TQ are critically reviewed. We overview molecular pharmacology to gain insight into the underlying mechanism of health benefits. Issues related to pharmacokinetic herb–drug interactions, drug delivery, and safety are also addressed. Identifying knowledge gaps, our current effort will direct future research to advance potential applications of black cumin and TQ in health and diseases.

Black cumin seed oil (BCSO) is the cold-pressed oil obtained from the seeds of Nigella sativa, Ranunculaceae. Nigella sativa is widely cultivated throughout southern Europe and the middle east for culinary and medicinal purposes. Recently, attention has been focused on BCSO as an edible oil with high nutritive value and role in human health attributed to high content in unsaturated fatty acids including linoleic and oleic acids among other components [1]. BSCO is available as a dietary supplement and marketed worldwide, which prompted to study the quality differences in the oil metabolome globally and conclude an association with geographic distribution. A total of 28 samples of marketed BSCO were collected from Egypt, Libya, Saudi Arabia, Ethiopia, Syria and Europe. The oils were analyzed using GC-MS carried out on a RTX-5MS column using temperature programming from 45 to 300 ° at 5 °/min rate and fatty acid composition was determined following the reported protocol [1]. A total of 125 of oil components were identified using Kovat's index and comparison of mass spectra to NIST Mass Spectral Library. The normalised GC peak areas were measured, expressed as percentages and 14 common components were used in the Principal Component Analysis (PCA) data set. The loading plot revealed the major peaks: linoleic acid (LA 0%-33.5%), oleic acid-methyl ester (OAM 7.3%-49.6%) and oleic acid (OA 0%-12.9%) as main chemical markers contributing to the segregation. The PCA score plot showed that most Egyptian samples were segregated above the line demarcating PC2 showing high concentrations in all three components while European, Ethiopian and Syrian samples were clearly segregated below the PC2 line with much lower values.

Transdermal drug delivery (TDD) systems offer a patient-friendly alternative to oral and injectable routes by enhancing bioavailability and bypassing hepatic first-pass metabolism. Nanoemulgels, which integrate nanoemulsions with gel matrices, provide improved drug solubilization, stability, and skin permeation. Incorporating both herbal components, such as Nigella sativa oil, and synthetic permeation enhancers, presents a synergistic strategy for enhancing the efficacy of anti-inflammatory agents like colchicine. This review critically evaluates the formulation, pharmacological benefits, and permeation- enhancing strategies of nanoemulgels containing colchicine. Literature was selected from major scientific databases, emphasizing studies that investigated the combined effects of herbal and synthetic excipients on drug delivery and therapeutic performance. Evidence indicates that nanoemulgels incorporating Nigella sativa oil and pharmaceuticalgrade permeation enhancers significantly improve colchicine's dermal absorption, sustain drug release, and reduce systemic toxicity. The synergistic interaction between natural bioactives and synthetic agents enhances both anti-inflammatory activity and skin permeability. The dual role of Nigella sativa as an anti-inflammatory and natural permeation enhancer, when paired with synthetic excipients, demonstrates superior pharmacodynamic outcomes. This integrated approach enhances the therapeutic index of colchicine while minimizing adverse effects. Combining herbal oils like Nigella sativa with pharmaceutical excipients in nanoemulgel systems represents a robust strategy for transdermal delivery. This platform improves drug penetration, stabilizes formulation performance, and amplifies therapeutic efficacy, offering a transformative alternative for chronic inflammatory conditions such as gout.

Introduction: Authentic kefir originates from the Caucasus mountains of Eastern Europe and is a fermented milk product made from kefir grains. Authentic kefir contains lactic acid bacteria, acetic acid bacteria and yeasts which provides kefir with numerous health benefits such as anticarcinogenic, antimutagenic and anti-allergic properties. Nigella sativa is a plant known by many regional names such as black cumin and black carraway. Seeds from the plant are processed to produce black seed oil. Black seed oil has many potential health benefits such as antibacterial and antifungal capabilities. In countries including Turkey and India, black seed oil is commonly added to kefir or yogurt. The purpose of this study was to determine if different concentrations of black seed oil would negatively impact beneficial kefir microorganisms when consumers mix black seed oil into kefir. Results: Black seed oil concentrations of 0%, 0.1%, 1% and 5% were added to milk with kefir grains and incubated. Each mixture was tested for pH, Lactobacillus spp., Lactococcus spp., yeast, and coliform microbial counts. Results indicated that the pH and microbial counts of the control (0%) and 0.1% black seed oil samples were not significantly different (P > 0.05). The pH and microbial count results of 1% black seed oil in kefir indicated slight although not significant inhibition (P > 0.05) as compared to the control and 0.1% black seed oil. The pH and microbial counts of 5% black seed oil were significantly different (P < 0.05) from the other samples indicating inhibition of the kefir microorganisms.Conclusion:Black seed oil inhibited kefir microorganism when added at the rate of 5%.Keywords: Kefir, Black Seed Oil, Lactobacillus spp., Lactococcus spp., Yeast, Probiotic

Dyslipidemia is an established risk factor for ischemic heart disease. Nigella sativa (NS) is a medicinal plant that has been used for the treatment and prevention of a variety of diseases, in particular hyperlipidemia. We reviewed the existing literature published until 2014 by using the following keywords: ''Nigella sativa'', ''black cumin'', ''black seeds'', ''thymoquinone'', and ''lipid''. In the conducted studies, different preparations of NS including seed powder (100mg-20g daily), seed oil (20-800mg daily), thymoquinone (3.5-20mg daily), and seed extract (methanolic extract especially), were shown to reduce plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides, but the effect on high-density lipoprotein cholesterol (HDL-C) was not significant. NS and thymoquinone have been reported to be safe and well tolerated with no severe adverse effect. In clinical trials, NS was found to be effective when added as adjunct to standard antihyperlipidemic and antidiabetic medications. Lipid-modifying effects of NS could be attributed to the inhibition of intestinal cholesterol absorption, decreased hepatic cholesterol synthesis, and up-regulation of LDL receptors. Overall, the evidence from experimental and a clinical studies suggests that NS seeds are a promising natural therapy for dyslipidemic patients.

Introduction: Chronic inflammatory diseases, including obesity, diabetes, cancer, asthma, and cardiovascular disorders, remain major causes of global morbidity and mortality. Conventional Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are widely used but often cause serious adverse effects with long-term use. Nigella sativa (black cumin), a traditional medicinal plant, has been recognized for its diverse pharmacological properties, particularly its anti-inflammatory potential. Methods: A literature search was conducted in PubMed, Scopus, and Web of Science for peerreviewed articles and clinical studies published up to 2024. Studies reporting on phytochemical constituents, pharmacological activities, and mechanisms of action of Nigella sativa were analyzed. Results: Evidence indicates that Nigella sativa exhibits broad-spectrum pharmacological activities, including hepatoprotective, neuroprotective, gastroprotective, antioxidant, antimicrobial, and anticancer effects. Notably, its bioactive compound thymoquinone plays a central role in modulating inflammation, oxidative stress, immune responses, and metabolic regulation. Preclinical and limited clinical findings also suggest beneficial effects in asthma, diabetes, and cardiovascular health. Discussion: While findings support the therapeutic versatility of Nigella sativa, the majority of evidence is derived from experimental and preclinical models. Clinical data remain insufficient, highlighting the need for rigorous, large-scale human trials to validate efficacy and safety. Conclusion: Nigella sativa shows promise as a safe, multi-targeted natural anti-inflammatory agent. Its integration into modern therapeutics could offer novel alternatives for managing chronic inflammatory diseases, pending confirmation through high-quality clinical research.