The effect of Nigella sativa supplementation on glycemic status in adults: An updated systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis of randomized controlled trials (RCTs) sought to evaluate the effects of Nigella sativa (N. sativa) consumption on glycemic index in adults. A systematic literature search up to December 2023 was completed in PubMed, Scopus, and Web of Science, to identify eligible RCTs. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as weighted mean differences with a 95 % confidence interval. Finally, a total of 30 studies were found to be eligible for this meta-analysis. The pooled results using random effects model indicated that N. sativa supplementation significantly reduced FBS (SMD: -1.71; 95 % CI: -2.11, -1.31, p <0.001; I2= 92.7 %, p-heterogeneity <0.001) and HA1c levels (SMD: -2.16; 95 % CI: -3.04, -1.29, p <0.001; I2= 95.7 %, p-heterogeneity <0.001) but not effect on insulin (SMD = 0.48; 95 % CI: -0.53, 1.48, P = 0.353; I2= 96.1 %, p-heterogeneity <0.001), and HOMA-IR (SMD: -0.56; 95 % CI: -1.47, 0.35, p=0.229; I2= 95.0 %, p-heterogeneity <0.001).Overall, the evidence supports the consumption of N. sativa to reduce FBS and HA1c levels. Additional research, featuring extended durations and robust study designs, is necessary to determine the ideal dosage and duration of N. sativa supplementation for achieving a positive impact on glycemic markers.

Role of Thymoquinone on sleep restriction and its mitigating effect on leptin-mediated signaling pathway in rat brain.

BACKGROUND: Sleep and stress interact bidirectionally by acting on brain circuits that affect metabolism. Sleep and its alterations have impact on blood leptin levels, metabolic hormone that regulates appetite. Brain expresses the receptors for the peptide hormone leptin produced from adipocytes. The hypothalamic orexin neurons are low during sleep and active when awake, influenced by a complex interaction with leptin. Thymoquinone was found to be the major bioactive component of Nigella sativa. The aim of this study was to study the role of thymoquinone on sleep restriction and its mitigating effect on leptin-mediated signaling pathway in rat brain. METHODS AND RESULTS: 30 adult male Wistar rats were divided into 5 groups with 6 animals in each group: Control; Thymoquinone (TQ); Corn oil; Chronic Sleep restriction (CSR); and CSR + TQ. After 30 days, behavioral analysis, antioxidant, lipid profile, glucose level, liver and kidney function test, neurotransmitters, neuropeptides, and mRNA expression in in vivo studies were also assessed and pharmacokinetic and docking were done for thymoquinone. Thymoquinone has also shown good binding affinity to the target proteins. CSR has induced oxidative stress in the discrete brain regions and plasma. Current study has shown many evidences that sleep restriction has altered the neurobehavioral, antioxidant status, lipid profile, neurotransmitters, neuropeptide levels, and feeding behavior which damage the Orexin-leptin system which regulates the sleep and feeding that leads to metabolic dysfunction. CONCLUSION: The potentiality of Thymoquinone was revealed in in silico studies, and its action in in vivo studies has proved its effectiveness. The study concludes that Thymoquinone has exhibited its effect by diminishing the metabolic dysfunction by its neuroprotective, antioxidant, and hypolipidemic properties.

Variation in the Composition and Quality of Nigella sativa L. Seed Oils-The Underestimated Impact on Possible Health-Promoting Properties.

Nigella sativa L. (black cumin) is one of the most investigated medicinal plants in recent years. Volatile compounds like thymoquinone and unsaponifiable lipid compounds are crucial functional components of this oil. Unfortunately, the composition of oils and their quality indicators are ambiguous both in terms of identified compounds and value ranges. Thirteen oils were extracted with hexane from black cumin seeds grown in India, Syria, Egypt, and Poland and analyzed for their fatty acid composition, unsaponifiable compound content and volatile compounds. Oils were also subjected to quality tests according to standard methods. The fatty acid composition and sterol content/composition were relatively stable among the tested oils. Tocol content varied in the range of 140-631 mg/kg, and among them, ß-tocotrienol and γ-tocopherol prevailed. Oils' volatile compounds were dominated by seven terpenes (p-cymene, α-thujene, α-pinene, ß-pinene, thymoquinone, γ-terpinene, and sabinene). The highest contents of these volatiles were determined in samples from Poland and in two of six samples from India. High acid and peroxide values were typical features of N. sativa L. oils. To sum up, future research on the medicinal properties of black cumin oil should always be combined with the analysis of its chemical composition.

Enhancement of Female Rat Fertility via Ethanolic Extract from Nigella sativa L. (Black Cumin) Seeds Assessed via HPLC-ESI-MS/MS and Molecular Docking.

The characteristic chemical composition of Nigella seeds is directly linked to their beneficial properties. This study aimed to investigate the phytochemical composition of Nigella sativa seeds using a 100% ethanolic extract using HPLC-ESI-MS/MS. Additionally, it explored the potential biological effects of the extract on female rat reproduction. Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estrogen (E2), and Progesterone (P4) hormone levels were also assessed, along with the morphological and histological effects of the extract on ovarian, oviductal, and uterine tissues. Molecular docking was performed to understand the extract's activity and its role in regulating female reproduction by assessing its binding affinity to hormonal receptors. Twenty metabolites, including alkaloids, saponins, terpenes, flavonoids, phenolic acids, and fatty acids, were found in the ethanolic extract of N. sativa seeds through the HPLC-ESI-MS/MS study. The N. sativa seed extract exhibited strong estrogenic and LH-like activities (p < 0.05) with weak FSH-like activity. Furthermore, it increased the serum levels of LH (p < 0.05), P4 hormones (p < 0.001), and E2 (p < 0.0001). Molecular docking results displayed a strong interaction with Erß, LH, GnRH, and P4 receptors, respectively. Based on these findings, N. sativa seeds demonstrated hormone-like activities, suggesting their potential as a treatment for improving female fertility.

Turmeric-Black Cumin Essential Oils and Their Capacity to Attenuate Free Radicals, Protein Denaturation, and Cancer Proliferation.

Turmeric rhizomes (Curcuma longa) and black cumin seeds (Nigella sativa) are polyherbal ingredients used for the management of cancer and other chronic inflammatory diseases in Nigerian ethnomedicine. Previous studies have shown the antioxidant, anti-inflammatory, and anticancer activities of the individual plant extracts. However, the two spices have not been biologically potentiated in their combined form. Therefore, this study obtained essential oils (EOs) from the combined spices and evaluated their inhibitory effects on free radicals, protein denaturation, and cancer proliferation. The EOs were extracted by hydro-distillation (HD) and characterized by gas chromatography-mass spectrometry (GC-MS). In vitro antioxidant assessment was conducted based on DPPH, hydrogen peroxide (H2O2), nitric oxide (NO), and ferric ion (Fe3+) radical scavenging assays. The cytotoxicity of the oil against non-tumorigenic (HEK293) and cancerous (HepG2 and HeLa) cell lines was determined following the MTT cell viability assay. An in silico molecular docking analysis of the oil constituents was also performed. Six batches of EOs I-VI were afforded, comprising twenty-two major constituents, with aromatic Ar-turmerone being the most prominent compound. There was a marked improvement in the bioactivity of the oils upon repeated HD and as a combination. The batch VI oil exhibited the best activity, with a cytotoxicity (CC50) of 10.16 ± 1.69 µg/100 µL against the HepG2 cell line, which was comparable to 5-fluorouracil (standard, CC50 = 8.59 ± 1.33 µg/100 µL). In silico molecular docking suggested δ-curcumene, Ar-curcumene, Ar-turmerol, and Ar-turmerone among the promising compounds based on their high binding energy scores with NOX2, NF-κB, and mdm2 proteins. In conclusion, the oils from the turmeric-black cumin combined possess a considerable inhibition ability against free radicals, protein denaturation, and cancer proliferation. This study's findings further underscore the effectiveness of turmeric-black cumin as a polyherbal medicinal ingredient.

Nigella sativa L. and its bioactive and nutraceutical components in the management of diabetic peripheral neuropathy.

Diabetes-induced hyperglycemia leads to excessive production of oxygen free radicals, inflammatory cytokines, and oxidative stress, which initiates diabetic peripheral neuropathy (DPN). Currently, this condition affects 20% of adults with diabetes. Despite significant advances in the treatment of diabetes, the incidence of its complications, including DPN, is still high. Thus, there is a growing research interest in developing more effective and treatment approaches with less side effects for diabetes and its complications. Nigella sativa L. (NS) has received much research attention as an antioxidant, anti-yperglycemic factor, and anti-inflammatory agent. This natural compound demonstrates its antidiabetic neuropathy effect through various pathways, including the reduction of lipid peroxidation, the enhancement of catalase and superoxide dismutase enzyme activity, and the decrease in inflammatory cytokine levels. The present review focuses on the bioactive and nutraceutical components of black cumin (Nigella sativa L.) and their effects on DPN. In addition, we have also summarized the findings obtained from several experimental and clinical studies regarding the antidiabetic neuropathy effect of NS in animal models and human subjects.

Prevention of Chronic Diabetic Neuropathy and Diabetes-Associated Cognitive Impairment Using Medicinal Herbs (Cassia Angustifolia and Nigella Sativa).

Nodal regions, areas of intensive contact between Schwann cells and axons, may be exceptionally vulnerable to diabetes-induced changes because they are exposed to and impacted by the metabolic implications of diabetes. Insulin receptors, glucose transporters, Na+ and K+ channels, and mitochondria are abundant in nodes, all of which have been linked to the development and progression of Diabetic Peripheral Neuropathy (DPN) and Type 1 Diabetes Mellitus (T1DM)-associated cognitive impairment. Our study aimed to evaluate if the administration of Nigella sativa (NS) and Cassia angustifolia (CA) prevented diabetes-associated nervous system deficits in hyperglycemic mice. We developed T1DM mice through Streptozotocin (STZ) injections and validated the elevations in blood glucose levels. NS and CA were administered immediately upon the induction of diabetes. Behavioral analysis, histopathological evaluations, and assessment of molecular biomarkers (NR2A, MPZ, NfL) were performed to assess neuropathy and cognitive impairment. Improvements in memory, myelin loss, and the expression of synaptic proteins, even with the retention of hyperglycemia, were evident in the mice who were given a dose of herbal products upon the detection of hyperglycemia. NS was more beneficial in preventing memory impairments, demyelination, and synaptic dysfunction. The findings indicate that including these herbs in the diets of diabetic as well as pre-diabetic patients can reduce complications associated with T1DM, notably diabetic peripheral neuropathy and cognitive deficits associated with T1DM.

Nutrient utilization, growth performance, and antioxidative status of Barki lambs fed diets supplemented with black (Nigella sativa) and rocket (Eruca sativa) seeds.

The current study aimed to determine the polyphenol compounds in Nigella sativa (NS) and Eruca sativa (ES) seeds, and evaluate the impact of their addition either as a sole additive or in combination on the growth performance, digestibility, some rumen and blood parameters and antioxidative status of Barki lambs. Forty-eight male lambs (27.18 ± 0.22 kg, 5-6 months), were divided into 4 balanced groups. The experimental diets were randomly distributed to the control group (CON); fed alfalfa hay plus concentrate feed mixture at a ratio of 30:70% without additives, while, NSD, ESD, and NESD groups: fed CON diet plus 2% NS, 2% ES or 1% NS + 1% ES, respectively as a ratio from total mixed ration (TMR). Results indicated that rutin and catechin were the most phenolic compounds observed either in NS or ES seeds. The NS and ES-supplemented groups recorded the highest (P < 0.05) values for dry matter digestibility, nutritive values, average daily gain, and the best feed conversion ratio. However, growth performance, nutritive value, and all nutrient digestibility except for dry matter were not significantly altered with the NESD group. Concentrations of ruminal NH3-N and TVFA were significantly (P < 0.05) reduced with the NESD group, with no significant differences in pH values among different groups. Values of blood parameters showed significant increases in WBCs, PCV, and T-AOC, and decreases in cholesterol, triglycerides, and MDA with the addition of NS and ES seeds or both. Therefore, the addition of NS and ES seeds is recommended to improve lambs' health and antioxidant status.

In vivo experimentally study the effect of Nigella Sativa silver nanoparticles for treatment of salmonella species causing diarrhea in ruminants.

Salmonellais one of the main etiological agents of infectious diarrhea in large and small ruminants but emergence of multidrug-resistant (MDR) strains faster rate than previously, leads to develop of MDR strains among animals needs different alternative therapeutic strategies. Our study was aimed to evaluate the effects of Nigella sativa silver nanoparticles (NS AgNPs) on specific pathogen-free (SPF) Wister rats. Nigella sativa silver nanoparticles were prepared and confirmed their formation by optical observations, UV-Vis spectroscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Rats in group G2 were infected experimentally with Salmonella spp and treated with ciprofloxacin orally for duration of 6 days at a dose rat 10 mg/kg. On the other hand, rats in group G1 were infected with salmonella and treated for 20 days with NS AgNPs in oral dose of (10 mg/kg rats), and the results were compared to control groups G3 which received bacterial infection without treatment and G4 control negative. The results of optical observation, UV-Vis spectroscopy, TEM, and SEM revealed typical characteristics of prepared NS AgNPs. Liver, kidney function biomarkers, hematologic analysis, and histological examination the tissues of liver, kidney, and stomach of rat's model improved that NS AgNPs has antimicrobial effect and has the ability to decrease the inflammatory reaction caused by Salmonella spp infection. The results of our study indicate that NS AgNPs are effective in controlling MDR Salmonella spp in vivo without causing any adverse effects. Moreover, our findings suggest that reducing the use of antimicrobials could be a key factor in the fight against antimicrobial resistance and can provide valuable insights into identifying the most appropriate treatment strategies to tackle this issue effectively in the future.

Gas Chromatography-Mass Spectrometry Detection of Thymoquinone in Oil and Serum for Clinical Pharmacokinetic Studies.

Thymoquinone (TQ) is the primary component of Nigella sativa L. (NS) oil, which is renowned for its potent hepatoprotective effects attributed to its antioxidant, anti-fibrotic, anti-inflammatory, anti-carcinogenic, and both anti- and pro-apoptotic properties. The aim of this work was to establish a method of measuring TQ in serum in order to investigate the pharmacokinetics of TQ prior to a targeted therapeutic application. In the first step, a gas chromatography-mass spectrometry method for the detection and quantification of TQ in an oily matrix was established and validated according to European Medicines Agency (EMA) criteria. For the assessment of the clinical application, TQ concentrations in 19 oil preparations were determined. Second, two serum samples were spiked with TQ to determine the TQ concentration after deproteinization using toluene. Third, one healthy volunteer ingested 1 g and another one 3 g of a highly concentrated NS oil 30 and 60 min prior to blood sampling for the determination of serum TQ level. After the successful establishment and validation of the measurement method, the highest concentration of TQ (36.56 g/L) was found for a bottled NS oil product (No. 1). Since a capsule is more suitable for oral administration, the product with the third highest TQ concentration (No. 3: 24.39 g/L) was used for all further tests. In the serum samples spiked with TQ, the TQ concentration was reliably detectable in a range between 5 and 10 µg/mL. After oral intake of NS oil (No. 3), however, TQ and/or its derivatives were not detectable in human serum. This discrepancy in detecting TQ after spiking serum or following oral ingestion may be attributed to the instability of TQ in biomatrices as well as its strong protein binding properties. A pharmacokinetics study was therefore not viable. Studies on isotopically labeled TQ in an animal model are necessary to study the pharmacokinetics of TQ using alternative modalities.

Diversity of Cationic Antimicrobial Peptides in Black Cumin (Nigella sativa L.) Seeds.

Black cumin (Nigella sativa L.) is known to possess a wide variety of antimicrobial peptides belonging to different structural families. Three novel antimicrobial peptides have been isolated from black cumin seeds. Two of them were attributed as members of the non-specific lipid transfer proteins family, and one as a defensin. We have made an attempt of using the proteomic approach for novel antimicrobial peptides search in N. sativa seeds as well. The use of a well-established approach that includes extraction and fractionation stages remains relevant even in the case of novel peptides search because of the lacking N. sativa genome data. Novel peptides demonstrate a spectrum of antimicrobial activity against plant pathogenic organisms that may cause economically important crop diseases. These results obtained allow considering these molecules as candidates to be applied in "next-generation" biopesticides development for agricultural use.

Biological Properties, Phenolic Profile, and Botanical Aspect of Nigella sativa L. and Nigella damascena L. Seeds: A Comparative Study.

The use of Nigella seeds in the food, pharmaceutical, and cosmetic fields is common, since the iniquity and the virtues of these plants are directly related to their characteristic phytochemical composition. This investigation focused on the comparative study of the botanical aspect, phenolic profile, and in vitro and in vivo biological activities of Nigella sativa L. (NS) and Nigella damascena L. (ND) seeds. The macro- and micro-morphological properties of these seeds were studied, and the key dissimilarities between them were clearly illustrated. The phytochemical contents and phenolic profiles were determined, and the in vitro antioxidant activity was assessed using four methods. The in vivo antioxidant and biochemical parameters of the blood of supplemented mice were determined. The results of the macro- and micro-structure analysis revealed differences between the two plants. Here, ND is characterized by higher phytochemical contents and the best antioxidant activities. The HPLC analysis indicated the presence of nine compounds, namely seven phenolic acids, particularly hydroxybenzoic and caffeic acids, and two flavonoids. The administration of ND extract to mice for 21 days at a concentration of 500 mg/kg allowed a substantial amelioration of plasma antioxidant properties. In addition, the extracts ameliorate blood parameters (cholesterol, triglycerides, glycemia, and urea). Furthermore, the antimicrobial activity of extracts demonstrated their effects on Staphylococcus and Aspergillus. Nigella seeds, in particular ND, expressed considerable in vitro antioxidant properties and demonstrated significant amelioration of mice blood properties. Consequently, these species can serve as a valuable source of compounds with various applications.

Effects of roasting and ultrasound-assisted enzymatic treatment of Nigella sativa L. seeds on thymoquinone in the oil and antioxidant activity of defatted seed meal.

BACKGROUND: Black cumin seeds (black seed; BS) contain various bioactive compounds, such as thymoquinone (TQ). Roasting and ultrasound-assisted enzymatic treatment (UAET) as pre-treatments can increase the phytochemical content in the BS oil. This study aimed to investigate the effects of pre-treatments on the TQ content and the yield of the BS oil and to profile the composition of defatted BS meal (DBSM), followed by evaluating antioxidant properties of the DBSM. RESULTS: The extraction yield of crude oil from BS was not affected by the roasting time. The highest extraction yield (47.8 ± 0.4%) was obtained with UAET cellulase-pH 5 (enzyme concentration of 100%). Roasting decreased the TQ content of the oil, while the UAET cellulase-pH 5 treatment with an enzyme concentration of 100% yielded the highest TQ (125.1 ± 2.7 µg mL-1 ). Additionally, the UAET cellulase-pH 5 treatment increased total phenolics and flavonoids of DBSM by approximately two-fold, compared to roasting or ultrasound treatment (UT) alone. Principal component analysis revealed that the UAET method might be more suitable for extracting BS oil with higher TQ content than roasting and UT. CONCLUSION: Compared to roasting or UT, using ultrasound along with cellulase could improve the oil yield and TQ in the oil from BS and obtain the DBSM with higher phenolics, flavonoids, and antioxidant activity. © 2023 Society of Chemical Industry.

In vitro study of Nigella sativa and thymoquinone activity on endothelial activation and monocyte adhesion.

INTRODUCTION: Thymoquinone (TQ) is one of the bioactive compounds in Nigella sativa (NS). Also known as black seeds/cumin, it has been postulated to possess anti-atherogenic properties. However, research on the effects of NS oil (NSO) and TQ on atherogenesis remain scarce. The aim of this study is to determine gene and protein expression of Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Endothelial-eukocyte adhesion molecule (E-selectin) in Human Coronary Artery Endothelial Cells (HCAECs). METHODS: HCAECs were stimulated for 24 hours (h) with 200 µg/ml of Lipopolysaccharides (LPS) and different concentrations of NSO (55, 110, 220, 440 µg/ml) or TQ (4.5, 9.0, 18.0, 36.0 µm). The effects of NSO and TQ on gene and protein expressions were measured using multiplex gene assay and ELISA assay, respectively. Rose Bengal assay was used to analyse monocyte binding activity. RESULTS: NSO and TQ significantly reduced ICAM-1 and VCAM-1 gene and protein expressions. TQ showed significant reduction activity of the biomarkers in dose dependent manner. HCAECs pre-treated with NSO and TQ for 24 h significantly lowered monocytes adherence compared to non-treated HCAECs. CONCLUSIONS: NSO and TQ supplementation have anti-atherogenic properties and inhibit monocytes' adherence to HCAECs via down-regulation of ICAM-1 expression. NSO could potentially be incorporated in standard treatment regimens to prevent atherosclerosis and its related complications.

Protective Effect of Nigella sativa and Onion Extract against 5-Fluorouracil-Induced Hepatic Toxicity.

Aim: The present study intended to compare the antioxidant, anti-lipid peroxidation, and anti-inflammatory potentials of Nigella Sativa (NS) and onion extract on 5-FU-induced liver damage in rats. Material and methods: 48 rats were divided into control, control group of the onion extract, control group of the NS extract, 5-FU-treated, concomitant NS-treated, and concomitant onion extract-treated. Liver sections were processed for histological analysis (light and electron microscopic examination). Liver enzymes (ALT, AST, and ALP), inflammatory markers (TNF-α and IL-1), antioxidant markers (SOD, GSH, and GSH/GSSG ratio), 4-HNE, NF-κB, and Nrf2 were evaluated. Results: The 5-FU-treated group exhibited inflammation, congested hepatic sinusoid, and steatosis. Improvement with few pathological residues was seen in the concomitant extract-treated groups. The 5-FU-treated group showed higher liver enzymes. The enzymes decreased in the concomitantly treated groups. 5-FU induced liver damage through oxidative stress, inflammation, and lipid peroxidation. Concomitantly using NS and onion extracts resulted in a reduction in oxidative stress, lipid peroxidation, and inflammation. Conclusion: NS and onion extracts attenuated 5-FU-induced liver damage via antioxidative, anti-lipid peroxidative, and anti-inflammatory mechanisms. NS's role was exceptional when compared with onion extract.

In vitro potential antiviral SARS-CoV-19- activity of natural product thymohydroquinone and dithymoquinone from Nigella sativa.

Inflammation, oxidation, and compromised immunity all increase the dangers of COVID-19, whereas many pharmaceutical protocols may lead to increased immunity such as ingesting from sources containing vitamin E and zinc. A global search for natural remedies to fight COVID-19 has emerged, to assist in the treatment of this infamous coronavirus. Nigella satvia is a world-renowned plant, an esteemed herbal remedy, which can be used as a liquid medicine to increase immunity while decreasing the dangers of acute respiratory distress syndrome. Thymoqinone (TQ), dithymoqinone (DTQ) and thymohydroquinone (THQ), are major compounds of the essential oil contained in N.sativa. A current study aims to discover the antiviral activity of two compounds, Thymohydroquinone and Dithymoquinone, which are synthesized through simple chemical procedures, deriving from thymoquinone, which happens to be a major compound of Nigella sativa. A half-maximal cytotoxic concentration, "CC50", was calculated by MTT assay for each individual drug, The sample showed anti-SARS-CoV-2 activity at non-cytotoxic nanomolar concentrations in vitro with a low selectivity index (CC50/IC50 = 31.74/23.15 = 1.4), whereby Dimthymoquinone shows high cytotoxicity.

Potential anticancer properties and mechanisms of thymoquinone in osteosarcoma and bone metastasis.

Despite great advances, therapeutic approaches of osteosarcoma, the most prevalent class of preliminary pediatric bone tumors, as well as bone-related malignancies, continue to demonstrate insufficient adequacy. In recent years, a growing trend toward applying natural bioactive compounds, particularly phytochemicals, as novel agents for cancer treatment has been observed. Bioactive phytochemicals exert their anticancer features through two main ways: they induce cytotoxic effects against cancerous cells without having any detrimental impact on normal cell macromolecules such as DNA and enzymes, while at the same time combating the oncogenic signaling axis activated in tumor cells. Thymoquinone (TQ), the most abundant bioactive compound of Nigella sativa, has received considerable attention in cancer treatment owing to its distinctive properties, including apoptosis induction, cell cycle arrest, angiogenesis and metastasis inhibition, and reactive oxygen species (ROS) generation, along with inducing immune system responses and reducing side effects of traditional chemotherapeutic drugs. The present review is focused on the characteristics and mechanisms by which TQ exerts its cytotoxic effects on bone malignancies.

Assessment of black cumin (Nigella sativa L.) as a food ingredient and putative therapeutic agent.

The whole or ground seeds of the food ingredient Nigella sativa L., known in Western culture as "black cumin" or "black caraway", has a three-millennial history of use in Middle- and Far-Eastern cultures as a food ingredient. The seed and its extracts have also been increasingly reported as a successful therapeutic agent with efficacy often attributed to the presence of the powerful antioxidant, thymoquinone. However, quantitative analysis of the seed (especially the volatile fraction) yields widely variable results, which may be due to one or a combination of different crop origins or possible varietal differences, contamination/adulteration, method of extraction, stage of maturation of the extracted seed and other factors. Nonetheless, despite the reported wide variability in bioactive constituents, many publications cite quantifiable outcomes in in vitro and in vivo toxicity testing and in clinical trials. There are a few reports describing allergic reactions in humans when N. sativa extracts are applied to the skin. Notwithstanding the foregoing, N. sativa seeds, used as a food ingredient at historical levels of consumption and as traditionally practiced are safe and Generally Recognized As Safe.

The Role of Thymoquinone in Inflammatory Response in Chronic Diseases.

Anti-inflammatory therapies have been shown to be effective in the prevention of various cardiovascular diseases, tumors, and cancer complications. Thymoquinone (TQ), the main active constituent of Nigella sativa, has shown promising therapeutic properties in many in vivo and in vitro models. However, TQ has poor bioavailability and is hydrophobic, prohibiting clinical trials with TQ alone. Studies have explored the combination of TQ with biological nanomaterials to improve its bioavailability. The TQ nanoparticle formulation shows better bioavailability than free TQ, and these formulations are ready for clinical trials to determine their potential as therapeutic agents. In this paper, we review current knowledge about the interaction between TQ and the inflammatory response and summarize the research prospects in Korea and abroad. We discuss the different biological activities of TQ and various combination therapies of TQ and nanomaterials in clinical trials.

Nigella sativa L. and COVID-19: A Glance at The Anti-COVID-19 Chemical Constituents, Clinical Trials, Inventions, and Patent Literature.

COVID-19 has had an impact on human quality of life and economics. Scientists have been identifying remedies for its prevention and treatment from all possible sources, including plants. Nigella sativa L. (NS) is an important medicinal plant of Islamic value. This review highlights the anti-COVID-19 potential, clinical trials, inventions, and patent literature related to NS and its major chemical constituents, like thymoquinone. The literature was collected from different databases, including Pubmed, Espacenet, and Patentscope. The literature supports the efficacy of NS, NS oil (NSO), and its chemical constituents against COVID-19. The clinical data imply that NS and NSO can prevent and treat COVID-19 patients with a faster recovery rate. Several inventions comprising NS and NSO have been claimed in patent applications to prevent/treat COVID-19. The patent literature cites NS as an immunomodulator, antioxidant, anti-inflammatory, a source of anti-SARS-CoV-2 compounds, and a plant having protective effects on the lungs. The available facts indicate that NS, NSO, and its various compositions have all the attributes to be used as a promising remedy to prevent, manage, and treat COVID-19 among high-risk people as well as for the therapy of COVID-19 patients of all age groups as a monotherapy or a combination therapy. Many compositions of NS in combination with countless medicinal herbs and medicines are still unexplored. Accordingly, the authors foresee a bright scope in developing NS-based anti-COVID-19 composition for clinical use in the future.