Biochemical effects of Nigella sativa L seeds in diabetic rats

Oral administration of ethanol extract of N. sativa seeds (300 mg/kg body weight/day) to streptozotocin induced diabetic rats for 30 days significantly reduced the elevated levels of blood glucose, lipids, plasma insulin and improved altered levels of lipid peroxidation products (TBARS and hydroperoxides) and antioxidant enzymes like catalase, superoxide dismutase, reduced glutathione and glutathione peroxidase in liver and kidney. The results confirm the antidiabetic activity of N. sativa seeds extract and suggest that because of its antioxidant effects its administration may be useful in controlling the diabetic complications in experimental diabetic rats.     

Effect of Nigella sativa and Foeniculum vulgare seeds extracts on male mice exposed to carbendazim

The increasing prevalence of environmental pollutants such as pesticides is a major global problem that affects living organisms. Exposure to environmental pollutants remains a major source of health risk throughout the world. The potential health benefits of various medicinal plants and natural products in relation to protect various diseases are currently receiving considerable attention. A current approach is to develop a new biological compound from natural products that inhibits pain. Ethnopharmacological surveys have been found to be one of the most reliable tools for the discovery of the natural and semi-synthetic drug. The present study was performed to investigate the hematological and biochemical changes induced by carbendazim (CBZ) and the potential protective effect of seeds extracts of Nigella sativa (NSSE) and Foeniculum vulgare (FVSE) against CBZ toxicity in male mice. Mice were distributed into 6 groups. Mice of group 1 were served as control. Group 2 was exposed to CBZ. Group 3 was supplemented with NSSE and exposed to CBZ. Group 4 was treated with FVSE and CBZ. Normal mice of group 5 and 6 were subjected to NSSE and FVSE respectively. Body weight gain was significantly decreased in mice of group 2. In mice of group 2, significant declines of RBC, HB, Hct, WBC, total protein, FSH, LH, testosterone, T4, T3, CAT and SOD were observed. Moreover, the levels of ALT, AST, ALP, total bilirubin, creatinine, BUN, uric acid, glucose, cholesterol, CK, LDH, MDA and GSH were significantly enhanced. Treatment with NSSE and FVSE showed attenuation effects against CBZ induced hematological and biochemical changes. The results suggest that the attenuation effects of NSSE and FVSE attributed to their antioxidant properties.     

A review on hypo-cholesterolemic activity of Nigella sativa seeds and its extracts

Nigella sativa (N. sativa) (Family Ranunculaceae) is a popular therapeutic herb in many parts of the world. It is widely used in traditional medical systems such as Unani, Ayurveda and Siddha. Seeds and oil have a long history of folkloric use in many medicinal and culinary systems. The seeds of N. sativa have long been used to treat a variety of illnesses and disorders. Studies on N. sativa and its therapeutic potential have been investigated. This includes anti-diabetic, anticancer, immune-modulatory, analgesic, antimicrobial, anti-inflammatory, spasmolytic, bronchodilator, hepato-protective, renal protective, gastro-protective, antioxidant properties, and several others. Nigella sativa contains thymoquinone. This is a bioactive component of the essential oil with medicinal benefits. Therefore, it is of interest to report a comprehensive data on the therapeutic usefulness of N. sativa in hypo-cholesterolemic activity.     

Activity and adsorption of lipase from Nigella sativa seeds on Celite at different pH values

Lipase from Nigella sativa seeds was immobilized by adsorption on Celite 535 from phosphate buffer solutions varying pH values of 5.0–8.0 at 25?°C. Langmuir isotherms described the adsorption equilibria well for lipase adsorption at all pH range. The saturation capacity for adsorption of lipase increased from 14.5 to 24.3 mg g^?1 Celite as the adsorption pH was reduced from 8 to 5, but the adsorption equilibrium constant remained constant and was determined to be 1.92 × 10⁵ M^?1. The adsorbed enzymes showed different activity values depending on the pH of the adsorption medium. The immobilized enzymes prepared at pH 6 displayed the highest activity values.     

Anti-inflammatuar and anti-oxidative effects of Nigella sativa L.: 18FDG-PET imaging of inflammation

Inflammation has an important role in many diseases such as cystic fibrosis, allergies and cancer. The free radicals produced during inflammation, can induce gene mutations and posttranslational modifications of cancer related proteins. Nigella sativa L. (N. sativa) is herbaceous plant and commonly used as a natural food. It has many pharmacological effects including antibacterial, antifungal, antitumor, analgesic, antipyretic activity. The aim of this study was to investigate the anti-inflammatuar and anti-oxidant activity of N. sativa in acute inflammation. Thus we used the experimental lipopolysaccharides (LPS)-induced model. Intraperitoneal LPS 1 mg/kg was administered to groups. N. sativa (500 mg/kg) and essential oil (5 ml/kg) were given orally to treatment groups, after 24-h of intraperitoneal LPS-injection. To determine the lung inflammation, ¹⁸F-fluoro-deoxy-d-glucose (0.8 ml/kg) was administrated under the anesthesia before the 1 h of PET-scanning. After the FDG-PET, samples were collected. Lung and liver ¹⁸F-FDG-uptake was calculated. Serum AST, ALT, LDH and hcCRP levels were determined and liver, lung and erythrocyte SOD, MDA and CAT levels were measured. Liver and lung NO and DNA fragmentation levels were determined. MDA levels were decreased in treated inflammation groups whereas increased in untreated inflammation group. SOD and CAT activities in untreated inflammation group were significantly lower. According to the control group, increased AST and ALT levels were found in untreated inflammation group. ¹⁸F-FDG uptake of inflammation groups were increased when compare the control group. We found increased ¹⁸F-FDG uptake, DNA fragmentation and NO levels in LPS-induced inflammation groups. We conclude that, in LPS-induced inflammation, N. sativa have therapeutic and anti-oxidant effects.     

Acylated dolabellane-type diterpenes from Nigella sativa seeds with triglyceride metabolism-promoting activity in high glucose-pretreated HepG2 cells

Two new acylated dolabellane-type diterpenes, nigellamines B₃ (9) and D (10), were isolated from Nigella sativa (Ranunculaceae) seeds using column chromatography and preparative HPLC. Their structures were determined based on chemical and physicochemical evidence, and confirmed using previously isolated related compounds as reference. Of the seed constituents, nigellamines A₂ (2), A₃ (3), A₅ (5), B₁ (6), and B₂ (7) had in vitro triglyceride metabolism-promoting activities in the high glucose-pretreated human liver carcinoma cell line, HepG2.     

Indazole-type alkaloids from the seeds of Nigella glandulifera

Two rare indazole-type alkaloids, nigeglapine (1) and nigeglaquine (2) along with one known compound (3), were isolated from the seeds of Nigella glandulifera. Their structures were confirmed on the basis of chemical and spectroscopic methods, mainly NMR (¹H, ¹³C, HSQC, HMBC and NOESY) and ESI-MS, and comparison with data in the literature. This is the first report of the natural occurrence of glycosylated indazole-type alkaloids.     

Differentiation of Nigella sativa seeds from four different origins and their bioactivity correlations based on NMR-metabolomics approach

Authenticity and quality coherence are the major elements in ensuring the consistency of the expected beneficial outcomes from the use of traditional or herbal remedies. Metabolomics offers the possibility of addressing these issues. Principal Component Analysis (PCA) was applied to select the best solvent system for sample extraction. Partial Least Square (PLS) regression analysis was found useful in evaluating the relationship between Nigella sativa seeds from four different origins on the basis of their metabolite profiles. In this study, different bioactivities were displayed by different samples with the Qasemi and Syrian samples exhibited high α-glucosidase inhibitory activity, which was correlated to the high fatty acid contents based on the PLS model. The Ethiopian sample exhibited high DPPH radical scavenging and nitric oxide (NO) inhibition activities, which may be related to the presence of high levels of thymoquinone and thymol. The method was also successfully used to classify “new test” samples into their proper groups.     

Nigella sativa (black cumin) seed extract alleviates symptoms of allergic diarrhea in mice, involving opioid receptors

The incidence of food hypersensitivity and food allergies is on the rise and new treatment approaches are needed. We investigated whether N. sativa, one of its components, thymoquinone, or synthetic opioid receptor (OR)-agonists can alleviate food allergy. Hence, ovalbumin (OVA)-sensitized BALB/c-mice were pre-treated either with a hexanic N. sativa seed extract, thymoquinone, kappa-(U50'4889) or mu-OR-agonists (DAMGO) and subsequently challenged intra-gastrically with OVA. All 4 treatments significantly decreased clinical scores of OVA-induced diarrhea. N. sativa seed extract, thymoquinone, and U50'488 also decreased intestinal mast cell numbers and plasma mouse mast cell protease-1 (MMCP-1). DAMGO, in contrast, had no effect on mast cell parameters but decreased IFNγ, IL-4, IL-5, and IL-10 concentration after ex vivo re-stimulation of mesenteric lymphocytes. The effects on allergy symptoms were reversible by OR-antagonist pre-treatment, whereas most of the effects on immunological parameter were not. We demonstrate that N. sativa seed extract significantly improves symptoms and immune parameters in murine OVA-induced allergic diarrhea; this effect is at least partially mediated by thymoquinone. ORs may also be involved and could be a new target for intestinal allergy symptom alleviation. N. sativa seed extract seems to be a promising candidate for nutritional interventions in humans with food allergy.     

Ameliorative effect of Nigella sativa conjugated silver nanoparticles against chromium-induced hepatotoxicity and renal toxicity in mice

Hexavalent chromium induces oxidative stress in the liver and kidney. Therefore an in vivo study was designed to investigate the modulatory effect of biosynthesized AgNP against Cr (VI) induced hepatotoxicity and nephrotoxicity. The organs index, serum level of ALT, AST, ALP, MDA, total protein and creatinine were measured. The histopathology and micrometry of the liver and kidney were examined. The liver index was significantly increased (0.098 ± 0.13 g) with slight increase in kidney index in Cr exposed group. The serum level of ALT (163.0 ± 5.5 U/L), AST (484.0 ± 10.7 U/L), ALP (337.6 ± 9.6 U/L), MDA (641.2 ± 29.2 U/L), and creatinine (2.9 ± 0.2 mg/dL) were significantly increased (P ≤ 0.05) with significant decrease in total protein level (2.9 ± 0.2 g/dL) (P ≤ 0.05) in chromium treated group. In histopathology, distorted hepatic cords, necrosis, damaged glomerulus and Bowman’s capsule were observed. Micrometric studies of the liver and kidney showed significant increase in size of hepatocytes (1188.2 ± 467.7 µ²) and their nuclei (456.4 ± 206.7 µ²), ACSA of Bowman’s capsule (11835.5 ± 336.7 µ²) and glomerulus (9051.8 ± 249.8 µ²⁾ in Cr (VI) treated group. The size of brush border (10.1 ± 3.0 µ) was significantly reduced in Cr (VI) treated group however the ACSA of lumen was not significantly changed. With the administration of NSSE and Nigella sativa AgNPs, decreased the oxidative damage caused by Cr (V).     

Validated high-performance thin-layer chromatographic method for the quantification of thymoquinone in Nigella Sativa extracts and formulations

Introduction – The surge of interest in naturally occurring phytochemicals with anticancer potential has led to the discovery of many molecules, one of them being thymoquinone (TQ) the bioactive constituent of the volatile oil of black seed, Nigella sativa L. (NS). Objective – The aim of the present work was to develop and validate an HPTLC method for determination of TQ in NS extracts, commercially available marketed oils, polyherbal formulations and in lipid‐based oral and parenteral formulations prepared in‐house. Methodology – Analysis of TQ was performed on TLC aluminium plates pre‐coated with silica gel 60F‐254. Linear ascending development was carried out in twin trough glass chamber, saturated with mobile phase consisting of toluene–cyclohexane (8 : 2, v/v) at ambient temperature. Camag TLC scanner III was used for the spectrodensitometric scanning and analysis in absorbance mode at 254 nm. Results – The method was found to give compact spots for TQ (R_f value of 0.28 ± 0.05) and was linear over the range 100–1400 ng/spot (r² = 0.9921 ± 0.0020). Accuracy, precision and repeatability were all within the required limits. The mean recoveries measured at three concentrations were higher than 95% with RSD ≤ 3%. Conclusion – The HPTLC method developed was found to be relatively simple, rapid and accurate for the routine analysis of TQ in extracts, marketed oils, polyherbal and in‐house formulations. Copyright © 2011 John Wiley & Sons, Ltd.     

Protective effects of thymoquinone and desferrioxamine against hepatotoxicity of carbon tetrachloride in mice

The effects of thymoquinone (TQ) and desferrioxamine (DFO) against carbon tetrachloride (CCl4)-induced hepatotoxicity were investigated. A single dose of CCl4 (20 microl/kg, i.p.) induced hepatotoxicity, manifested biochemically by significant elevation of activities of serum enzymes, such as alanine transaminase (ALT, EC: 2.6.1.2) , aspartate transaminase (AST, EC: 2.6.1.1) and lactate dehydrogenase (LDH, EC: 1.1.1.27). Hepatotoxicity was further evidenced by significant decrease of total sulfhydryl (-SH) content, and catalase (EC: 1.11.1.6) activity in hepatic tissues and significant increase in hepatic lipid peroxidation measured as malondialdhyde (MDA). Pretreatment of mice with DFO (200 mg/kg i.p.) 1 h before CCl4 injection or administration of TQ (16 mg/kg/day, p.o.) in drinking water, starting 5 days before CCl4 injection and continuing during the experimental period, ameliorated the hepatotoxicity induced by CCl4, as evidenced by a significant reduction in the elevated levels of serum enzymes as well as a significant decrease in the hepatic MDA content and a significant increase in the total sulfhydryl content 24 h after CCl4 administration. In a separate in vitro assay, TQ and DFO inhibited the non-enzymatic lipid peroxidation of normal mice liver homogenate induced by Fe3+/ascorbate in a dose-dependent manner. These results indicate that TQ and DFO are efficient cytoprotective agents against CCl4-induced hepotoxicity, possibly through inhibition of the production of oxygen free radicals that cause lipid peroxidation.     

Cannabidiol, a constituent of Cannabis sativa, modulates sleep in rats

Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabidiol (CBD) are two major constituents of Cannabis sativa. Delta(9)-THC modulates sleep, but no clear evidence on the role of CBD is available. In order to determine the effects of CBD on sleep, it was administered intracerebroventricular (icv) in a dose of 10 microg/5 microl at the beginning of either the lights-on or the lights-off period. We found that CBD administered during the lights-on period increased wakefulness (W) and decreased rapid eye movement sleep (REMS). No changes on sleep were observed during the dark phase. Icv injections of CBD (10 microg/5microl) induced an enhancement of c-Fos expression in waking-related brain areas such as hypothalamus and dorsal raphe nucleus (DRD). Microdialysis in unanesthetized rats was carried out to characterize the effects of icv administration of CBD (10 microg/5 microl) on extracellular levels of dopamine (DA) within the nucleus accumbens. CBD induced an increase in DA release. Finally, in order to test if the waking properties of CBD could be blocked by the sleep-inducing endocannabinoid anandamide (ANA), animals received ANA (10 microg/2.5 microl, icv) followed 15 min later by CBD (10 microg/2.5 microl). Results showed that the waking properties of CBD were not blocked by ANA. In conclusion, we found that CBD modulates waking via activation of neurons in the hypothalamus and DRD. Both regions are apparently involved in the generation of alertness. Also, CBD increases DA levels as measured by microdialysis and HPLC procedures. Since CBD induces alertness, it might be of therapeutic value in sleep disorders such as excessive somnolence.     

Identification of SARS-CoV-2 RNA-dependent RNA polymerase inhibitors from the major phytochemicals of Nigella sativa: An in silico approach

The coronavirus disease 2019 (COVID-19), which emerged in December 2019, continues to be a serious health concern worldwide. There is an urgent need to develop effective drugs and vaccines to control the spread of this disease. In the current study, the main phytochemical compounds of Nigella sativa were screened for their binding affinity for the active site of the RNA-dependent RNA polymerase (RdRp) enzyme of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The binding affinity was investigated using molecular docking methods, and the interaction of phytochemicals with the RdRp active site was analyzed and visualized using suitable software. Out of the nine phytochemicals of N. sativa screened in this study, a significant docking score was observed for four compounds, namely α-hederin, dithymoquinone, nigellicine, and nigellidine. Based on the findings of our study, we report that α-hederin, which was found to possess the lowest binding energy (–8.6 kcal/mol) and hence the best binding affinity, is the best inhibitor of RdRp of SARS-CoV-2, among all the compounds screened here. Our results prove that the top four potential phytochemical molecules of N. sativa, especially α-hederin, could be considered for ongoing drug development strategies against SARS-CoV-2. However, further in vitro and in vivo testing are required to confirm the findings of this study.     

Phytochemical,biochemical, and growth changes in response to salinity in callus cultures of Nigella sativa L.

Black cumin (Nigella sativa L.) is considered as a noteworthy herbal medicine. However, no study has been conducted on the physiological adaptive mechanism of it to salinity stress, especially under in vitro condition. To this aim, the callus cultures of ten different genotypes of N. sativa were applied to evaluate the changes occurring in biochemical traits under salinity stress. The calluses were exposed to the in vitro salt stress using different sodium chloride concentrations (0, 84, and 250 mM). A reduction occurred in the content of K⁺ and callus growth by enhancing the NaCl concentration. However, most of the content of Na⁺ (4 mgg^− 1 DW), malondialdehyde (1.38 μmolg^− 1 FW), total phenolic content (1.18 mg GAEg⁻¹ FW), thymol (25.26 mgg^− 1 DW), total flavonoids content (0.06 mg QEg^− 1 FW), total flavonols (TFL) content (0.023 mg QEg^− 1 FW), total anthocyanins (Ant) (0.05 μmol g^− 1 FW) and DPPH activity (58.17%) was observed at 250 mM of NaCl. In fact, two secondary metabolites including TFL and Ant can be considered as the major contributors to the potential antioxidant activity of N. sativa at the callus level. The elicitation through NaCl opens new avenues for the selection of best dosages of NaCl for the enhancement of commercially important secondary metabolites, in superior genotypes (Nig₁ and Nig₂) of N. sativa at cellular level.

     

Pharmacological intervention of biosynthesized Nigella sativa silver nanoparticles against hexavalent chromium induced toxicity in male albino mice

Hexavalent chromium, toxic heavy metal, among the top-rated environmental contaminants, is declared a potent endocrine disruptor in humans and animals. The present study was planned to find harmful effects on the reproductive system caused by Cr (VI) and the ameliorative effect of Nigella sativa and Nigella sativa-mediated AgNP on male mice (Mus musculus). In the present study, known infertility medicine, clomiphene citrate is also used as a positive control. The main objective of the present study was to assess the ameliorative potential of oral administration of a dose of 50 mg/kg BW clomiphene citrate (control), AgNP via chemical synthesis, Nigella sativa seed extract, and Nigella sativa-mediated AgNP against the Cr (VI) at the dose of 1.5 mg/kg BW from K₂Cr₂O₇ orally induced toxicity over eight weeks on the reproductive performance of male albino mice. Nigella sativa mediated AgNPs were characterized by UV, SEM, FTIR, and XRD. The histological analysis, smear study, antioxidant capacity test, and hormone analysis were conducted by blood samples of albino mice. Cr exposed groups showed a significant decrease in sperm head breadth (5.29 ± 0.54 µ) and length (19.54 ± 1.18 µ), middle piece length, tail length, LH (1.65 ± 0.15 ng/mL), testosterone (2.63 ± 0.29 ng/mL), SOD (61.40 ± 2.48 mmol/mL), CAT (87.40 ± 6.01 mmol/mL), GSH (1.54 ± 0.09 µmol/mL), and no of spermatogonia (1.22 ± 0.25), and spermatocytes (2.33 ± 0.943). However, FSH level (160.00 ± 4.98 ng/mL), seminiferous tubule CSA (1094.69 ± 49.76 mm²), size of spermatogonia (41.30 ± 1.24 µ), and spermatocytes (26.07 ± 1.34 µ) were significantly increased. Administration of Nigella sativa and Nigella sativa-mediated AgNPs reduced the toxicity.     

Morphogenesis in Tissue Cultures of Different Organs of Nigella sativa

Calli were isolated from root, stem and leaf segments of Nigella sativa (Fam. Ranunculaceae) on White's medium containing napthaleneacetic acid and coconut milk. From all the three types of calli, roots were differentiated. Shoot development occurred in stem and leaf calli only after the omission of first coconut milk and then of auxin from the basal medium and also in IAA (2.0 mg/ml) and coconut milk (15 % v/v) in the medium. Frequency of organ formation and the maintenance of this capacity depend upon the nature as well as the age of the callus tissue.     

The effects of Nigella sativa on bile duct ligation induced‐liver injury in rats

Nigella sativa (NS) has been shown to have antioxidant and antiinflammatory activities in different conditions. The goal of this study was to evaluate the effects of NS on cholestatic liver injury in rats. Thirty rats were recruited in the study as follows: Group 1, Bile duct ligation (BDL) (n = 10); Group 2, BDL plus NS (n = 10); and Group 3, Sham (n = 10). Bile duct ligated group received 0.2 mL kg^?1 dose of NS intraperitoneally daily throughout 14 days. Liver damage and cholestasis were determined by the biochemical and the pathologic examination. Data showed a decrease in gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities of the NS treated rats when compared with BDL group (p < 0.001 for GGT and p < 0.05 for others). The NS treated rats' tissue levels of total oxidant status (TOS), oxidative stress index (OSI), and myeloperoxidase (MPO) were significantly lower than that of the BDL group (p < 0.01 for all). Increases in total antioxidant capacity (TAC) and catalase (CAT) levels were statistically significant in the NS treated rats compared to BDL group (p < 0.01 for both). On the other hand, administration of NS in the rats with biliary obstruction resulted in inhibition of necro‐inflammation. These results indicate that NS exerts a therapeutic effect on cholestatic liver injury in bile duct ligated rats possibly through attenuation of enhanced neutrophil infiltration and oxidative stress in the liver tissue. Copyright © 2009 John Wiley & Sons, Ltd.     

Chemical composition of the fixed and volatile oils of Nigella sativa L. from Iran

The chemical composition of the extracted fixed oil (total fatty acid composition) and volatile oil of Nigella sativa L. seeds grown in Iran were determined by GC and GC/MS. Eight fatty acids (99.5%) and thirty-two compounds (86.7%) have been identified in the fixed and volatile oils, respectively. The main fatty acids of the fixed oil were linoleic acid (55.6%), oleic acid (23.4%), and palmitic acid (12.5%). The major compounds of the volatile oil were trans-anethole (38.3%), p-cymene (14.8%), limonene (4.3%), and carvone (4.0%).