Particulate air pollution (PAP) exposure is associated with increased morbidity and mortality, particularly in patients with renal disease. However, there are only a few studies on the interaction between PAP and renal injury, and none on agents that may ameliorate it. We studied the interaction between cisplatin (CP) nephrotoxicity and a single exposure to diesel exhaust particle (DEP) in rats 24”‰h before sacrifice, and assessed the effect of co-treatment with the active ingredient in Nigella Sativa seed oil, thymoquinone (TQ) thereon. Rats were injected intraperitoneally with CP (6”‰mg/kg) and four days later, they were exposed intratracheally to DEP (0.5”‰mg/kg), and were sacrificed 24”‰h later. Oral TQ (20”‰mg/kg) was given daily throughout the experimental period. CP alone caused several physiological, biochemical, and histopathological changes that included reduced growth and creatinine clearance, and raised plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL-6) and C-reactive protein (CRP), creatinine and urea concentrations, and urinary N-acetyl-b-D-glucosaminidase (NAG) activities. It adversely affected several indices of oxidative damage in the kidneys, and induced renal tubular necrosis. Most of these actions were significantly potentiated in rats given both CP and DEP. TQ significantly abrogated many of the effects of CP and DEP, given alone and in combination. These results provide experimental evidence that subjects with renal diseases can be at higher risk from PAP, and that TQ, pending further pharmacological and toxicological studies, can be considered a useful agent in patients with renal diseases and exposed to PAP.

Thymoquinone (TQ) is the primary bioactive component of Nigella sativa Linn seed oil and used as anti-inflammatory, anti-oxidant, and anti-neoplastic agent. Previous studies have shown that TQ exhibits inhibitory effects on multiple cancers. However, the detailed antineoplastic effects and its molecular mechanisms of TQ on lung cancer are not entirely elucidated yet. In the present study, we aimed to investigate the effects of TQ on cell proliferation, migration, and invasion as well as its underlying anti-metastatic mechanisms in A549 cells. Lung cancer cell line A549 cells were treated with different concentration of TQ for different period of time, and the growth-inhibitory effects of TQ was measured by MTT and cell count assays; cell cycle was determined by flow cytometry; wound healing and transwell assays were used to assess the cell migration and invasion activities; Western blot and real-time quantitative RT-PCR were used to determine the expression of proliferation and invasion associated genes as well as MAPKs pathway molecules; gelatinase activity was estimated using gelatin zymography assay. The results show that TQ played a role in inhibiting the proliferation, migration, and invasion of A549 lung cancer cells, it also inhibited the expression level of PCNA, cyclin D1, MMP2, and MMP9 mRNA and protein in a dose- and time-dependent manner especially at 10, 20, 40 Î¼mol/L concentrations. The cell cycle inhibitor P16 expression and the gelatinase activities of MMP2 and MMP9 were also inhibited by TQ dramatically. TQ reduced phosphorylation of ERK1/2; however, the proliferation and invasion inhibitory effects of TQ on A549 cells were neutralized by ERK1/2 inhibitor PD98059. In conclusion, our study confirmed that TQ could inhibit A549 cell proliferation, migration, and invasion through ERK1/2 pathway, as proposed the therapeutic potential of TQ as an anti-metastatic agent in human lung cancer treatment. 

Nigella sativa (N sativa), commonly known as black seed, has been used in traditional medicine to treat many diseases. The antioxidant, anti-inflammatory, and antibacterial activities of N sativa extracts are well known. Therefore, the present study was designed to investigate the anticancer activity of seed extract (NSE) and seed oil (NSO) of N sativa against a human lung cancer cell line. Cells were exposed to 0.01 to 1 mg/ml of NSE and NSO for 24 h, then percent cell viability was assessed by 3-(4, 5-dimethylthiazol-2yl)-2, 5-biphenyl tetrazolium bromide (MTT) and neutral red uptake (NRU) assays, and cellular morphology by phase contrast inverted microscopy. The results showed NSE and NSO significantly reduce the cell viability and alter the cellular morphology of A-549 cells in a concentration dependent manner. The percent cell viability was recorded as 75%, 50%, and 26% at 0.25, 0.5, and 1 mg/ml of NSE by MTT assay and 73%, 48%, and 23% at 0.25, 0.5, and 1 mg/ml of NSE by NRU assay. Exposure to NSO concentrations of 0.1 mg/ml and above for 24 h was also found to be cytotoxic. The decrease in cell viability at 0.1, 0.25, 0.5, and 1 mg/ml of NSO was recorded to be 89%, 52%, 41%, and 13% by MTT assay and 85%, 52%, 38%, and 11% by NRU assay, respectively. A-549 cells exposed to 0.25, 0.5 and 1 mg/ml of NSE and NSO lost their typical morphology and appeared smaller in size. The data revealed that the treatment of seed extract (NSE) and seed oil (NSO) of Nigella sativa significantly reduce viability of human lung cancer cells. 

BACKGROUND:

Thymoquinone (TQ) is a compound extracted from Black Caraway seeds of Nigella Sativaand is active against various cancers. Cisplatin (CDDP) is the most active chemotherapeutic agent in LungCancer. Here we report activity of TQ against non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines alone and in combination with Cisplatin (CDDP).

RESULTS:

TQ was able to inhibit cell proliferation, reduce cell viability and induce apoptosis. …. TQ down regulated NF-kappaB expression which may explain its various cellular activities and this activity may prove useful in overcoming CDDP resistance from over expression of NF-kappaB.

CONCLUSIONS:

Thus TQ and CDDP appear to be an active therapeutic combination in lung cancer.

In previous studies, the relaxant, anticholinergic (functional antagonism) antihistaminic, effects of Nigella sativahave been demonstrated on guinea-pig tracheal chains. In the present study, the prophylactic effect of boiled extract of N. sativa on asthmatic disease was examined. Twenty-nine asthmatic adults were randomly divided into control group (14 patients) and study group (15 patients), and they were studied for 3 months. In the study group 15 mL/kg of 0.1 g% boiled extract and in the control group a placebo solution was administrated daily throughout the study. Asthma symptom score, asthma severity, frequency of symptoms/week and wheezing were recorded in the beginning (first visit), 45 days after treatment (second visit), and at the end of the study (third visit). Pulmonary function tests (PFTs) were also measured, and the drug regimen of the patients was evaluated at three different visits. All asthma symptoms, frequency of asthma symptoms/week, chest wheezing, and PFT values in the study group significantly improved in the second and third visits compared with the first visit (P < 0.05 to P < 0.001). In addition, further improvement of chest wheezing and severity of disease on the third visit were observed compared with the second visit in this group (P < 0.05 for both cases). In the third visit all symptoms in the study group were significantly different from those of the control group (P < 0.01 to P < 0.001). However, in the control group, there were only small improvements in some parameters in just the second visit. The usage of inhaler and oral beta-agonists, oral corticosteroid, oral theophylline and even inhaler corticosteroid in the study group decreased at the end of the study while there were no obvious changes in usage of the drugs in control subjects. The results of phase I study generally suggest a prophylactic effect of N. sativa on asthma disease and warrant further research regarding this effect.

It has been reported that Nigella sativa oil possesses anti-inflammatory and bronchodilator activities. Besides, non – toxic and wide margin of safety for therapeutic doses compared with Dexamethasone. This work aims to study the effect of Nigella sativa and Dexamethason on different immune and inflammatory parameters in a mouse model of allergic asthma. Mice sensitized intraperitoneally and challenged intratracheally with conalbumin were treated with Nigella sativa 24 hours after the first intratracheal challenge. Dexamethasone treated and naïve mice served as controls. The effect of Nigella sativa and Dexamethasone treatment on peripheral blood eosinophil count, IgG1 and IgG2a, cytokine profiles and lung inflammation were evaluated. Nigella sativa was significantly reduced peripheral blood eosinophil count, IgG1 and IgG2a levels, cytokine profiles and inflammatory cells in lung tissue. These effects were equivalent to the effects of Dexamethasone except unchanged IFN-y level. Nigella sativa exhibits anti-airway inflammation and immunoregulatory effect which may be useful for treatment of allergic asthma.