Anti-tumor properties of blackseed (Nigella sativa L.) extracts

Abstract The objective of the present study was to evaluate the in vitro and in vivo anti-cancer effect of Nigella sativa L. seed extracts. The essential oil (IC 50 = 0.6%, v/v) and ethyl acetate (IC 50 = 0.75%) extracts were more cytotoxic against the P815 cell line than the butanol extract (IC 50 = 2%). Similar results were obtained with the Vero cell line. Although all extracts had a comparable cytotoxic effect against the ICO1 cell line, with IC 50 values ranging from 0.2 to 0.26% (v/v), tests on the BSR cell line revealed a high cytotoxic effect of the ethyl acetate extract (IC 50 = 0.2%) compared to the essential oil (IC 50 = 1.2%). These data show that the cytotoxicity of each extract depends on the tumor cell type. In vivo, using the DBA2/P815 (H 2 d ) mouse model, our results clearly showed that the injection of the essential oil into the tumor site significantly inhibited solid tumor development. Indeed, on the 30th day of treatment, the tumor volume of the control animals was 2.5 ± 0.6 cm 3 , whereas the tumor volumes of the essential oil-treated animals were 0.22 ± 0.1 and 0.16 ± 0.1 cm 3 when the animals were injected with 30 µL (28.5 mg)/mouse and 50 µL (47.5 mg)/mouse per 48 h (six times), respectively. Interestingly, the administration of the essential oil into the tumor site inhibited the incidence of liver metastasis development and improved mouse survival. Correspondence A. Zya

Anti-tumor properties of black seed (Nigella Sativa)extract

Abstract The objective of the present study was to evaluate the in vitro and in vivo anti-cancer effect of Nigella sativa L. seed extracts. The essential oil (IC 50 = 0.6%, v/v) and ethyl acetate (IC 50 = 0.75%) extracts were more cytotoxic against the P815 cell line than the butanol extract (IC 50 = 2%). Similar results were obtained with the Vero cell line. Although all extracts had a comparable cytotoxic effect against the ICO1 cell line, with IC 50 values ranging from 0.2 to 0.26% (v/v), tests on the BSR cell line revealed a high cytotoxic effect of the ethyl acetate extract (IC 50 = 0.2%) compared to the essential oil (IC 50 = 1.2%). These data show that the cytotoxicity of each extract depends on the tumor cell type. In vivo, using the DBA2/P815 (H 2 d ) mouse model, our results clearly showed that the injection of the essential oil into the tumor site significantly inhibited solid tumor development. Indeed, on the 30th day of treatment, the tumor volume of the control animals was 2.5 ± 0.6 cm 3 , whereas the tumor volumes of the essential oil-treated animals were 0.22 ± 0.1 and 0.16 ± 0.1 cm 3 when the animals were injected with 30 µL (28.5 mg)/mouse and 50 µL (47.5 mg)/mouse per 48 h (six times), respectively. Interestingly, the administration of the essential oil into the tumor site inhibited the incidence of liver metastasis development and improved mouse survival

In vitro cytotoxic, antioxidant, hemolytic and cytoprotective potential of promising ethacrynic acid derivatives

The present study aims to screen some pharmacological activities of three promising ethacrynic acid (EA) derivatives (P3, P4, and P5) containing a piperazine moiety. The EA derivatives were tested against MDA-MB-468 cancer cell line as a model for the triple-negative breast cancer and MCF7 cancer cell line as a model subtype of luminal breast cancer using the methyl tetrazolium test (MTT). Additionally, the modulation of the glutathione and thioredoxin enzymatic systems, as well as the antioxidant and cytoprotective potential of each compound, were investigated. Moreover, initial in vitro safety screening was conducted using human blood cells. As a result, EA derivatives showed clear dose-dependent antiproliferative activity in the micromolar range (between 1.13 and 2.51 uM), with high selectivity to cancer cells by orchestrating oxidative stress. Derivative P3 has the most promising potential for further preclinical investigation, owing to its safety profile and significant cytoprotective and antitumor properties

Acute toxicity of essential oils of two Moroccan endemic species: Thymus broussonetii and Thymus leptobotrys

Abstract Thymus species essential oils are widely used in aromatherapy to treat several ailments. However, there is no report on their safety. In this study, we propose to investigate the acute toxicity of T. leptobotrys and T. broussonetii essential oils. These two species were selected on the basis of their frequency of medicinal use and commercial importance. Chemical analysis of these two species essential oil revealed that thymol, borneol, carvacrol and p-cymene were the main chemical constituents in T. broussonetii, whereas the essential oil of T. leptobotrys contains carvacrol (98 %) as the major component. In the acute toxicity assay, the animals showed no stereotypical symptoms associated with toxicity such as convulsion, ataxy, diarrhoea or increased diuresis. The calculated median lethal dose (LD 50 ) was estimated at 4.47 g/kg for T. broussonetii and 2.66 g/kg for T. leptobotrys

Cytotoxic effect of essential oil of thyme (Thymus broussonettii) on the IGR-OV1 tumor cells resistant to chemotherapy

The anti-tumor effect of the Moroccan endemic thyme (Thymus broussonettii) essential oil (EOT) was investigated in vitro using the human ovarian adenocarcinoma IGR-OV1 parental cell line OV1/P and its chemoresistant counterparts OV1/adriamycin (OV1/ADR), OV1/vincristine (OV1/VCR), and OV1/cisplatin (OV1/CDDP). All of these cell lines elicited various degrees of sensitivity to the cytotoxic effect of EOT. The IC50 values (mean ± SEM, v/v) were 0.40 ± 0.02, 0.39 ± 0.02, 0.94 ± 0.05, and 0.65 ± 0.03% for OV1/P, OV1/ADR, OV1/VCR, and OV1/CDDP, respectively. Using the DBA-2/P815 (H2d) mouse model, tumors were developed by subcutaneous grafting of tumor fragments of similar size obtained from P815 (murin mastocytoma cell line) injected in donor mouse. Interestingly, intra-tumoral injection of EOT significantly reduced solid tumor development. Indeed, by the 30th day of repeated EOT treatment, the tumor volumes of the animals were 2.00 ± 0.27, 1.35 ± 0.20, and 0.85 ± 0.18 cm³ after injection with 10, 30, or 50 µL per 72 h (six times), respectively, as opposed to 3.88 ± 0.50 cm³ for the control animals. This tumoricidal effect was associated with a marked decrease of mouse mortality. In fact, in these groups of mice, the recorded mortality by the 30th day of treatment was 30 ± 4, 18 ± 4, and 8 ± 3%, respectively, while the control animals showed 75 ± 10% of mortality. These data indicate that the EOT which contains carvacrol as the major component has an important in vitro cytotoxic activity against tumor cells resistant to chemotherapy as well as a significant antitumor effect in mice. However, our data do not distinguish between carvacrol and the other components of EOT as the active factor

Inborn disorders of the malate aspartate shuttle

Over the last few years, various inborn disorders have been reported in the malate aspartate shuttle (MAS). The MAS consists of four metabolic enzymes and two transporters, one of them having two isoforms that are expressed in different tissues. Together they form a biochemical pathway that shuttles electrons from the cytosol into mitochondria, as the inner mitochondrial membrane is impermeable to the electron carrier NADH. By shuttling NADH across the mitochondrial membrane in the form of a reduced metabolite (malate), the MAS plays an important role in mitochondrial respiration. In addition, the MAS maintains the cytosolic NAD+ /NADH redox balance, by using redox reactions for the transfer of electrons. This explains why the MAS is also important in sustaining cytosolic redox-dependent metabolic pathways, such as glycolysis and serine biosynthesis. The current review provides insights into the clinical and biochemical characteristics of MAS deficiencies. To date, five out of seven potential MAS deficiencies have been reported. Most of them present with a clinical phenotype of infantile epileptic encephalopathy. Although not specific, biochemical characteristics include high lactate, high glycerol 3-phosphate, a disturbed redox balance, TCA abnormalities, high ammonia, and low serine, which may be helpful in reaching a diagnosis in patients with an infantile epileptic encephalopathy. Current implications for treatment include a ketogenic diet, as well as serine and vitamin B6 supplementation