Thymoquinone (TQ) and diosgenin (DG), the active ingredients obtained from black cumin (Nigella sativa) and fenugreek (Trigonella foenum graecum), respectively, exert potent bioactivity, including anticancer effects. This study investigated the antineoplastic activity of these agents against squamous cell carcinoma in vitro and sarcoma 180–induced tumors in vivo. TQ and DG inhibited cell proliferation and induced cytotoxicity in A431 and Hep2 cells. These agents induced apoptosis by increasing the sub-G1 population, LIVE/DEAD cytotoxicity, chromatin condensation, DNA laddering and TUNEL-positive cells significantly (P<0.05). Increased Bax/Bcl-2 ratio, activation of caspases and cleavage of poly ADP ribose polymerase were observed in treated cells. These drugs inhibited Akt and JNK phosphorylations, thus inhibiting cell proliferation while inducing apoptosis. In combination, TQ and DG had synergistic effects, resulting in cell viability as low as 10%. In a mouse xenograft model, a combination of TQ and DG significantly (P<0.05) reduced tumor volume, mass and increased apoptosis. TQ and DG, alone and in combination, inhibit cell proliferation and induce apoptosis in squamous cell carcinoma. The combination of TQ and DG is a potential antineoplastic therapy in this common skin cancer.
Over many centuries humans have been mining the bounties of nature for discovering substances that have been used for the treatment of all human diseases; many such remedies are useful even today as modern day medicine. Emerging evidence also suggests that the search is still continuing for harnessing active compounds from nature in combating human illnesses although pharmaceutical industries are equally active for synthesizing small molecule compounds as novel therapeutics. The lesson learned over many centuries clearly suggests that further sophisticated search for finding compounds from natural resources together with robust characterization and chemical synthesis will lead to the discovery of novel drugs that may have high therapeutic efficacy against all human diseases including cancer. Black cumin seed (Nigella sativa) oil extracts have been used for many centuries for the treatment of many human illnesses, and more recently the active compound found in black seed oil, viz. thymoquinone (TQ) has been tested for its efficacy against several diseases including cancer. However, further research is needed in order to assess the full potential of TQ as a chemopreventive and/or therapeutic agent against cancers. Here, we have summarized what is known regarding the value of black seed oil and its active compound TQ, and how this knowledge will help us to advance further research in this field by creating awareness among scientists and health professionals in order to appreciate the medicinal value of TQ and beyond.
Thymoquinone; Chemoprevention; Chemotherapy
Thymoquinone, a component derived from the medial plant Nigella sativa, has been used for medical purposes for more than two thousands of years. Recent studies reported that thymoquinone exhibited inhibitory effects on cell proliferation of many cancer cell lines and hormone-refractory prostate cancer by suppressing androgen receptor and E2F-1. Whether thymoquinone inhibits angiogenesis, the critical step of tumor growth and metastasis, is still unknown. In this study, we found that thymoquinone effectively inhibited human umbilical vein endothelial cell (HUVEC) migration, invasion, and tube formation. Thymoquinone inhibited cell proliferation and suppressed the activation of AKT and ERK. Thymoquinone blocked angiogenesis in vitro and in vivo, prevented tumor angiogenesis in a xenograft human prostate cancer (PC3) model in mouse and inhibited human prostate tumor growth at low dosage with almost no chemotoxicitical side effects. Furthermore, we observed that endothelial cells were more sensitive to thymoquinone-induced cell apoptosis, cell proliferation and migration inhibition compared to PC3 cancer cells. Thymoquinone inhibited VEGF-induced ERK activation, but showed no inhibitory effects on VEGF receptor 2 activation. Overall, our results indicate that thymoquinone inhibits tumor angiogenesis and tumor growth, and could be used as a potential drug candidate for cancer therapy.
thymoquinone; angiogenesis inhibitor; tumor angiogenesis; HUVEC
The use of innocuous naturally occurring compounds to overcome drug resistance and cancer recalcitrance is now in the forefront of cancer research. Thymoquinone (TQ) is a bioactive constituent of the volatile oil derived from seeds of Nigella sativa Linn. TQ has shown promising anti-carcinogenic and anti-tumor activities through different mechanisms. However, the effect of TQ on cell signaling and survival pathways in resistant cancer cells has not been fully delineated. Here, we report that TQ greatly inhibits doxorubicin-resistant human breast cancer MCF-7/DOX cell proliferation. TQ treatment increased cellular levels of PTEN proteins, resulting in a substantial decrease of phosphorylated Akt, a known regulator of cell survival. The PTEN expression was accompanied with elevation of PTEN mRNA. TQ arrested MCF-7/DOX cells at G2/M phase and increased cellular levels of p53 and p21 proteins. Flow cytometric analysis and agarose gel electrophoresis revealed a significant increase in Sub-G1 cell population and appearance of DNA ladders following TQ treatment, indicating cellular apoptosis. TQ-induced apoptosis was associated with disrupted mitochondrial membrane potential and activation of caspases and PARP cleavage in MCF-7/DOX cells. Moreover, TQ treatment increased Bax/Bcl2 ratio via up-regulating Bax and down-regulating Bcl2 proteins. More importantly, PTEN silencing by target specific siRNA enabled the suppression of TQ-induced apoptosis resulting in increased cell survival. Our results reveal that up-regulation of the key upstream signaling factor, PTEN, in MCF-7/DOX cells inhibited Akt phosphorylation, which ultimately causes increase in their regulatory p53 levels affecting the induction of G2/M cell cycle arrest and apoptosis. Overall results provide mechanistic insights for understanding the molecular basis and utility of the anti-tumor activity of TQ.
PTEN tumor suppressor; breast cancer; thymoquinone; apoptosis; cell signaling
Pancreatic cancer (PC) is one of the deadliest of all tumors. Previously, we were the first to show that Thymoquinone (TQ) derived from black seed (Nigella sativa) oil has anti-tumor activity against PC. However, the concentration of TQ required was considered to be high to show this efficacy. Therefore, novel analogs of TQ with lower IC50 are highly desirable.
We have synthesized a series of 27 new analogs of TQ by modifications at the carbonyl sites or the benzenoid sites using single pot synthesis and tested their biological activity in PC cells.
Among these compounds, TQ-2G, TQ-4A1 and TQ-5A1 (patent pending) were found to be more potent than TQ in terms of inhibition of cell growth, induction of apoptosis and modulation of transcription factor-NF-κB. We also found that our novel analogs were able to sensitize gemcitabine and oxaliplatin-induced apoptosis in MiaPaCa-2 (gemcitabine resistant) PC cells, which was associated with down-regulation of Bcl-2, Bcl-xL, survivin, XIAP, COX-2 and the associated Prostaglandin E2.
From our results, we conclude that three of our novel TQ analogs warrant further investigation against PC, especially in combination with conventional chemotherapeutic agents.
apoptosis; pancreatic cancer; thymoquinone; thymoquinone analogs
Previous studies on “Black seed” or “Black Cumin” Nigella sativa (NS) have reported a large number of pharmacological activities including its anti-ulcer potential. These studies employed either fixed oil, volatile oil components or different solvent extracts. In folkloric practices, NS seeds are taken as such, in the form of coarse dry powder or the powdered seeds are mixed with water. This study examines the effect of NS aqueous suspension on experimentally induced gastric ulcers and basal gastric secretion in rats to rationalize its use by herbal and Unani medicine practitioners.
Materials and Methods
The study was conducted at the Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Acute gastric ulceration was produced by various noxious chemicals (80% ethanol, 0.2 M NaOH, 25% NaCl and indomethacin) in Wistar albino rats. Anti-secretory studies were undertaken in a separate group of rats. Gastric wall mucus contents and non-protein sulfhydryl concentration were estimated, and gastric tissue was examined histopathologically.
An aqueous suspension of Black seed significantly prevented gastric ulcer formation induced by necrotizing agents. It also significantly ameliorated the ulcer severity and basal gastric acid secretion in pylorus-ligated Shay rats. Moreover, the suspension significantly replenished the ethanol-induced depleted gastric wall mucus content levels and gastric mucosal non-protein sulfhydryl concentration. The anti-ulcer effect was further confirmed histopathologically.
These findings validate the use of Black seed in gastropathies induced by necrotizing agents. The anti-ulcer effect of NS is possibly prostaglandin-mediated and/or through its antioxidant and anti-secretory activities.
Habbatul-Barakah; Nigella sativa; stomach; ulcer; gastric acid
Cancer remains one of the most dreaded diseases causing an astonishingly high death rate, second only to cardiac arrest. The fact that conventional and newly emerging treatment procedures like chemotherapy, catalytic therapy, photodynamic therapy and radiotherapy have not succeeded in reverting the outcome of the disease to any drastic extent, has made researchers investigate alternative treatment options. The extensive repertoire of traditional medicinal knowledge systems from various parts of the world are being re-investigated for their healing properties. This study progresses in the direction of identifying component(s) from Nigella sativa with anti cancer acitivity. In the present study we investigated the efficacy of Organic extracts of Nigella sativa seed powder for its clonogenic inhibition and induction of apoptosis in HeLa cancer cell.
Methanolic, n-Hexane and chloroform extracts of Nigella sativa seedz effectively killed HeLa cells. The IC50 values of methanolic, n-hexane, and chloroform extracts of Nigella sativa were 2.28 μg/ml, 2.20 μg/ml and 0.41 ng/ml, respectively. All three extracts induced apoptosis in HeLa cells. Apoptosis was confirmed by DNA fragmentation, western blot and terminal transferase-mediated dUTP-digoxigenin-end labeling (TUNEL) assay.
Western Blot and TUNEL results suggested that Nigella sativa seed extracts regulated the expression of pro- and anti- apoptotic genes, indicating its possible development as a potential therapeutic agent for cervical cancer upon further investigation.
Thymoquinone (TQ), derived from the medicinal spice Nigella sativa (also called black cumin), has been shown to exhibit anti-inflammatory and anti-cancer activities. In this report we employed polymer-based nanoparticle approach to improve upon its effectiveness and bioavailability. TQ was encapsulated with 97.5% efficiency in biodegradable nanoparticulate formulation based on poly (lactide-co-glycolide) (PLGA) and the stabilizer polyethylene glycol (PEG)-5000. Dynamic laser light scattering and transmission electron microscopy confirmed particle diameter ranged between 150–200 nm. Electrophoretic gel shift mobility assay showed that TQ nanoparticles (NP) were more active than TQ in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), markers of cell proliferation, metastasis and angiogenesis, respectively. TQ-NP was also more potent than TQ in suppressing proliferation of colon cancer, breast cancer, prostate cancer, and multiple myeloma cells. Esterase staining for plasma membrane integrity revealed that TQ-NP was more potent than TQ in sensitizing leukemic cells to TNF- and paclitaxel-induced apoptosis. Overall our results demonstrate that encapsulation of TQ into nanoparticles enhances its anti-proliferative, anti-inflammatory, and chemosensitizing effects.
Nanoparticles; Thymoquinone; Apoptosis; Inflammation; NF-κB
Thymoquinone (TQ) is a compound extracted from Black Caraway seeds of Nigella Sativa and is active against various cancers. Cisplatin (CDDP) is the most active chemotherapeutic agent in Lung Cancer. 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).
For proliferation MTT assay, cell viability trypan blue assay and for apoptosis Annexin-V FITC assay were used in NCI-H460 and NCI-H146 cell lines. Inhibition of invasion by TQ was assessed using Matrigel assay and its affect on release of various cytokines was determined using RayBio Human Cytokine detection kit. Mouse xenograft model using NCI-H460 was used to determine in vivo activity of TQ and CDDP. Inhibition of LPS induced NF-κB expression by TQ was determined using transgenic mice expressing a luciferase reporter.
TQ was able to inhibit cell proliferation, reduce cell viability and induce apoptosis. TQ at 100 μM and CDDP at 5 μM inhibited cell proliferation by nearly 90% and the combination showed synergism. TQ was able to induced apoptosis in both NCI-H460 and NCI-H146 cell lines. TQ also appears to affect the extracellular environment inhibiting invasion and reducing the production of two cytokines ENA-78 and Gro-alpha which are involved in neo-angiogenesis. Using a mouse xenograft model we were able to demonstrate that combination of TQ and CDDP was well tolerated and significantly reduced tumor volume and tumor weight without additional toxicity to the mice. In the combination arms (TQ5 mg/kg/Cis 2.5 mg/kg) tumor volume was reduced by 59% and (TQ20 mg/kg/Cis 2.5 mg/kg) by 79% as compared to control which is consistent with in vitro data. TQ down regulated NF-κB expression which may explain its various cellular activities and this activity may prove useful in overcoming CDDP resistance from over expression of NF-κB.
Thus TQ and CDDP appear to be an active therapeutic combination in lung cancer.
This study investigated antiepileptic effects of the main constituents of Nigella sativa (NS) seed (i.e. aqueous extract (AE), fixed oil (FO), volatile oil (VO)) and the main components of its VO (i.e. thymoquinone, α-pinene and p-cymene) using pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced convulsions. The potential of these constituents to induce minimal neurological deficit (MND) was also evaluated by using chimney test.
Except for the FO, all of the NS seed constituents protected mice effectively against PTZ-induced convulsions. The activity of the VO in this model maybe attributed mainly to its content of thymoquinone and p-cymene and to a lesser extent, α-pinene. VO and its component p-cymene effectively suppressed convulsions induced by MES. The contents of p-cymene present in the effective dose of the VO maybe partially responsible for its anti-seizure effects.
All of the NS seed constituents induced varying degrees of MND in the chimney test. MND induced by VO may pertain to its contents of thymoquinone (63%), p-cymene (23%) and α-pinene (<14%). Protective indices of p-cymene and thymoquinone were closer to one, but only in PTZ model.
Exploration on the role of receptors suggests that picrotoxin and bicuculline-sensitive GABA receptors, most probably GABAA receptors, mediate an increase in GABAergic response. In the part dealing with the interaction of valproate with thymoquinone, it can be mentioned that thymoquinone increased the potency of valproate in both PTZ and MES models.
Anticonvulsant; Maximal electroshock seizure; Nigella sativa; Pentylenetetrazole; Potentiation; Valproate
Many medicinal plants and their purified constituents have been shown beneficial therapeutic potentials. Seeds of Nigella sativa, a dicotyledon of the Ranunculaceae family, have been utilized for thousands of years as a spice and food preservative.
the toxic effect of aflatoxin-B1 (AFB1) and the possible cytoprotective effect of Nigella sativa (NS) oil and aqueous extract of date were studied on 40 male rats. The animals were divided into 4 groups (10 rats each) and treated daily for two weeks. Group 1 received normal saline as controls. Group 2 treated via intraperitoneal (IP) route with AFB1 (50μg/kg BW). Group 3 treated with AFB1 and NS oil via IP. Group 4 treated with AFB1 and received orally aqueous extract of date (15mg/15ml). The liver and kidneys of each animal were histological examined and biochemical evaluation of the liver and kidney functions was performed.
Group 2 showed severe degenerative and necrotic changes in the liver and kidney. The plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine and urea in AFB1 group were significantly higher than the control group. Livers and kidneys of rats, treated with AFB1 and NS showed less histopathological changes in comparison with the AFB1 treated group. Livers and kidneys of rats treated with AFB1 and date group showed only mild histopathological changes in comparison with AFB1 treated group. These histopathological changes seen in animals treated with AFB1 and dates were associated with a significant reduction in levels of ALT, AST, creatinine and urea. Likewise, histopathological changes in the AFB1 and NS group were associated with significant reduction in the levels of beforementioned indices. Moreover, AFB1 and date group showed significant improvement in liver function comparing with AFB1 and NS group.
our study revealed that treatment with AFB1 induced histopathological changes in the tissues of liver and kidney associated with dysfunction of these organs. Both NS and date reduce the toxic effects of AFB1 in liver and kidney. But date treatment was more cytoprotective for liver than NS treatment against aflatoxicosis in rats.
Nigella sativa; Date; Aflatoxin B1 toxicity; Liver; Kidney; rats
Nigella sativa or Black seed (N. sativa L.) is traditionally used for several ailments in many Middle Eastern countries. It is an annual herbaceous plant that belongs to the Ranuculacea family with many beneficial properties as antitumor, antidiabetic, antihypertensive, antioxidative and antibacterial. This work attempted to study the effect of N. sativa seeds powder and oil on atherosclerosis in diet-induced hypercholesterolemic (HC) rabbits in comparison with simvastatin (ST). Twenty-five adult New Zealand male white rabbits, weighing 1.5–2.5 kg, were divided into five groups; normal group (NC, n = 5) and four hypercholesterolemic groups (n = 20): a positive control (PC) and three HC groups force fed diet supplemented with 1000 mg Kg−1 body weight of N. sativa powder (NSP), 500 mg Kg−1 body N. sativa oil (NSO) and 10 mg Kg−1 ST for 8 weeks. Feeding HC rabbits with N. sativa either in powder or oil forms was shown to significantly reduce (P < .05) total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels and enhance high-density lipoprotein cholesterol (HDL) levels after treatment for 2, 4, 6 and 8 weeks compared to the PC group. Plaque formation was significantly inhibited while the intima: media ratio was significantly reduced in the NSP and NSO supplemented groups compared to the PC group. In conclusion, treatment of HC rabbits with N. sativa seeds powder or oil showed hypocholesterolemic and antiatherogenic cardioprotective properties.
Nigella sativa (N. sativa) is a herbal plant of the Ranunculaceae family that has been widely used for various medicinal and nutritional purposes. Volatile oil extracts along with its major constituents, such as thymoquinone, have recently attracted considerable attention for their antioxidant, immunoprotective and antitumor properties. The present study was conducted to assess the chemopreventive potential of crude oils in N. sativa on tumor formation using a well-established rat multi-organ carcinogenesis model featuring initial treatment with five different carcinogens. Post-initiation administration of 1000 or 4000 ppm N. sativa volatile oil in the diet of male Wistar rats for 30 weeks significantly reduced malignant and benign colon tumor sizes, incidences and multiplicities. The treatment also significantly decreased the incidences and multiplicities of tumors in the lungs and in different parts of the alimentary canal, particularly the esophagus and forestomach. Bromodeoxyuridine labeling indices, reflecting cell proliferation were significantly decreased in various organs and lesions after treatment with the two doses of N. sativa. The plasma levels of insulin growth factor, triglycerides and prostaglandin E2 were also altered. The findings show, for the first time, that N. sativa administration exerts potent inhibitory effects on rat tumor development and on cellular proliferation in multiple organ sites. In particular, the ability to significantly inhibit murine colon, lung, esophageal and forestomach tumors was demonstrated in the post-initiation phase, with no evidence of clinical side effects. The mechanisms are likely to be related to suppression of cell proliferation.
Nigella sativa; multi-organ carcinogenesis; rat; cancer
A decoction comprised of Nigella sativa seeds, Hemidesmus indicus root bark and Smilax glabra rhizome is being recommended for cancer patients by a family of traditional medical practitioners of Sri Lanka. Previous investigations have demonstrated that a short term (10 weeks) treatment with the decoction can significantly inhibit diethylnitrosamine (DEN) mediated expression of Glutathione S-transferase P form (GST-P) in rat liver. The objective of the present investigation was to determine whether long term (16 months) treatment with the decoction would be successful in inhibiting in rat livers, not only DEN- mediated expression of GST-P, but also the carcinogen mediated development of overt tumours (OT) or histopathological changes leading to tumour development (HT).
Thirty-six male Wistar rats were divided into 3 groups of 12 each. Groups 1 and 2 were injected intraperitoneally (i.p) with DEN (200 mg/kg) while group 3 was injected normal saline (NS). Twenty-four hours later, decoction (DC; 6 g/kg body weight/day) was orally administered to group 1 rats, while groups 2 and 3 (DEN-control and normal control) were given distilled water (DW). Treatment with DC or DW continued for 16 months. At the end of the 9th month and 16th months (study 1 and study 2 respectively), six rats from each group were sacrificed, and livers observed for OT or HT, both visually and by subjecting liver sections to staining with Haemotoxylin and Eosin (H & E), Sweet's Silver stain (for reticulin fibers), Periodic Acid Schiff (PAS) staining (for glycogen), and immunohistochemical staining (for GST-P).
At the end of 9 months (study 1) a hepatocellular adenoma (HA) developed in one of the rats in the DEN + DW treated group (group 2). At the end of 16 months (study 2), livers of all rats of group 2 developed OT and HT. Large areas of GST-P positive foci were also observed. No OT, HT or GST-P positive foci were detected in any of the other groups.
Protection against DEN-mediated carcinogenic changes in rat liver can be achieved by long term treatment with the DC comprised of N. sativa seeds, S. glabra rhizome and H. indicus root bark.
Oxidized low density lipoprotein plays an important role in development of foam cells in atherosclerosis. The study was focused on regulation of primary human monocyte growth and CD11b expression in presence of Nigella sativa oil.
Primary human monocytes were isolated from whole blood and grown at 37°C and 5% CO2 saturation for five days prior to treatment with Nigella sativa oil. The cells were plated and washed before treatment with ox-LDL (10 μg/ml) as positive control and combined treatment of ox-LDL (10 μg/ml) and (140 ng/ml) Nigella sativa oil. The growth progression was monitored every 24 hours for 3 days.
Macrophages showed reduced growth in comparison to monocytes 24 hours after treatment with Nigella sativa oil. The mean cell diameter was significantly different between untreated and treated condition in monocytes and macrophages (p < 0.001). Similarly, intracellular lipid accumulation was hindered in combined treatment with Nigella sativa oil. This was further supported by cell surface expression analysis, where CD11b was markedly reduced in cells treated with combination oxLDL and Nigella sativa oil compared to oxLDL alone. More cells differentiated into macrophage-like cells when monocytes were supplemented with oxidized LDL alone.
The finding provides preliminary evidence on regulation of cell growth and differentiation in monocyte and monocyte-derived macrophages by Nigella sativa oil. Further investigations need to be conducted to explain its mechanism in human monocyte.
A decoction comprised of Nigella sativa seeds, Hemidesmus indicus root and Smilax glabra rhizome is used to treat cancer patients in Sri Lanka. However, the anti-carcinogenic properties of this decoction have not been experimentally confirmed. The purpose of this study was to determine whether the above decoction could protect against chemically induce hepatocarcinogenesis.
The effects of this decoction on diethylnitrosamine (DEN) induced hepatocarcinogenesis were examined in male Wistar rats using the medium term bioassay system of Ito, based on a 2-step model of hepatocarcinogenesis. Rats were randomly divided into 6 groups of 10 each. Groups 1 to 4 were injected with DEN (200 mg/kg) to initiate carcinogenesis. Twenty-four hours later groups 1 and 2 were administered the decoction at 4 g/kg body weight/day (dose 1) and 6 g/kg body weight/day (dose 2), respectively. Group 3 and group 4 were given distilled water instead of the decoction and a suspension of garlic powder (20 g/kg body weight/day) in distilled water (positive control), respectively. Group 5 and 6 were injected with normal saline and twenty-four hours later group 5 was given distilled water (normal control) while group 6 was given decoction dose 2 (decoction control). Oral feeding continued for two weeks after which all rats were subjected to 2/3 partial hepatectomy to promote carcinogenesis. Oral feeding continued for eight more weeks. At the end of the 10th week, rats were sacrificed and samples of livers taken for immunohistochemical studies.
Carcinogenic potential was scored by comparing the number, area and staining intensity of glutathione S-transferase placental form (GST-P) positive foci and the number of cells/cm2 of the positive foci in the livers of the six groups of rats.
The number and area of DEN-mediated GST-P positive foci, number of cells/cm2 of foci and staining intensity of the foci were significantly (P > 0.001) reduced by the decoction and garlic in the order dose 2 = garlic >dose 1.
Overall results indicate that the decoction comprised of N. sativa, S. glabra and H. indicus has the potential to protect rat liver against DEN induced hepatocarcinogenesis
The seeds of the Nigella sativa plant have been used to promote health and fight disease for centuries, especially in the Middle East and in Southeast Asia. This plant has been a focus of much research. This clinical study was undertaken to know the adjuvant effect of N. sativa oil on various clinical and biochemical parameters of the insulin resistance syndrome.
MATERIALS AND METHODS:
This prospective study was conducted at a tertiary health care center in North India. After confirmation of diagnosis, 60 patients who fulfilled the inclusion and exclusion criteria were enrolled in this study. Written informed consent was taken from all the patients enrolled. Approval from the institutional ethical committee was also obtained. The patients were divided into two groups of 30 each. In group I (the standard group), patients were advised tablet atorvastatin 10 mg once a day and tablet metformin 500 mg twice a day for a period of 6 weeks. In group II (the N. sativa group), the patients were advised tablet atorvastatin 10 mg once a day, tablet metformin 500 mg twice a day, and N. sativa oil 2.5 ml twice daily for a period of 6 weeks. Fasting and postprandial blood glucose, fasting lipid profile, and waist circumference were recorded before therapy and after completion of therapy.
The treatment group showed significant (P < 0.05) improvement with reference to total cholesterol, low density lipoprotein cholesterol (LDL-C), and fasting blood glucose (P < 0.05).
N. sativa oil was found to be effective as an add-on therapy in patients of insulin resistance syndrome. N. sativa oil has a significant activity in diabetic and dyslipidemic patients.
Insulin resistance syndrome; Nigella sativa
Ten plants indigenous to Sudan and of common use in Sudanese folk-medicine, were examined in vitro for antimalarial activity against schizonts maturation of Plasmodium falciparum, the major human malaria parasite. All plant samples displayed various antiplasmodial activity. Three plant extracts caused 100% inhibition of the parasite growth at concentrations of plant material ≤ 500 ug/ml. The two most active extracts that produced 100% inhibition of the parasite growth at concentration of plant material ≤ 50 μg/ml were obtained from the seeds of Nigella sativa and the whole plant of Aristolochia bracteolata. The ten plants were phytochemically screened for their active constituents. The two most active plants showed the presence of sterols, alkaloids and tannins.
medicinal plants; antiplasmodial activity; folk-medicine
Nigella Sativa (NS) seeds have been used for medicinal purposes for centuries both as herbs and its oil. In Islam it is regarded as one of the greatest forms of healing medicine included in the medicine of prophet Mohammed. Huge number of studies have been carried out in recent years on the pharmacological effects of these seeds and also the possible relationship with their constituents. A number of these investigations emphasized the antimicrobial effect of them by using different extracts. In our study we have tried to use the normal human mechanism in digestion by using the ground seeds. A modified paper disc diffusion method was used to test the antibacterial effect of NS seeds. Clear inhibition of the growth of Staphylococcus aureus was observed by concentration of 300mg/ml with distilled water (D.W.) as control , this inhibition was confirmed by using the positive control Azithromycin. The inhibition obtained was higher with Nigella sativa ground seeds from Hadramout (HNSGS) than with Nigella sativa ground seeds from Ethiopia (ENSGS). No inhibition was found in the growth of E.Coli and Enterobacter. This was emphasized by using the positive control Ciprofloxacin. The positive inhibition may be attributed to the two important active ingredients of NS, Thymoquinone and melanin.
Nigella Sativa; antibacterial effect; Staphylococcus aureus; paper disc-diffusion method
Thymoquinone is an active principle of Nigella sativa seed known as "Habbah Al-Sauda" in Arabic countries and "Sinouj" in Tunisia. Bacterial biofilms tend to exhibit significant tolerance to antimicrobials drugs during infections.
The antibacterial activity of Thymoquinone (TQ) and its biofilm inhibition potencies were investigated on 11 human pathogenic bacteria. The growth and development of the biofilm were assessed using the crystal violet (CV) and the 2, 3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) reduction assay.
TQ exhibited a significant bactericidal activity against the majority of the tested bacteria (MICs values ranged from 8 to 32 μg/ml) especially Gram positive cocci (Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis CIP 106510). Crystal violet assay demonstrated that the minimum biofilm inhibition concentration (BIC50) was reached with 22 and 60 μg/ml for Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis CIP 106510 respectively. In addition our data revealed that cells oxidative activity was influenced by TQ supplementation. In the same way, TQ prevented cell adhesion to glass slides surface.
The ability of TQ to prevent biofilm formation warrants further investigation to explore its use as bioactive substances with antibiofilm potential.
Pancreatic cancer is one of the most lethal cancers in the world, as it continues to be resistant to any therapeutic approaches. The high molecular weight glycoprotein mucin 4 (MUC4) is aberrantly expressed in pancreatic cancer and contributes to the regulation of differentiation, proliferation, metastasis, and the chemoresistance of pancreatic cancer cells. The absence of its expression in the normal pancreatic ductal cells makes MUC4 a promising target for novel cancer therapeutics. Natural products have been widely investigated as potential candidates in cancer therapies, and thymoquinone (TQ), extracted from the seeds of Nigella sativa, has shown excellent antineoplastic properties in some systems. In the present study, we evaluated the effect of TQ on pancreatic cancer cells and specifically investigated its effect on MUC4 expression. The MUC4-expressing pancreatic cancer cells FG/COLO357 and CD18/HPAF were incubated with TQ, and in vitro functional assays were done. The results obtained indicate that treatment with TQ downregulated MUC4 expression through the proteasomal pathway and induced apoptosis in pancreatic cancer cells by the activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase pathways. In agreement with previous studies, the decrease in MUC4 expression correlated with an increase in apoptosis, decreased motility, and decreased migration of pancreatic cancer cells. MUC4 transient silencing studies showed that c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase pathways are activated in pancreatic cancer cells, indicating that the activation of these pathways by TQ is directly related to the MUC4 downregulation induced by the drug. Overall, TQ has potential for the development of novel therapies against pancreatic cancer.
Nigella sativa seeds (NS) has been used traditionally for various illnesses. The most abundant and active component of NS is thymoquinone (TQ). Animal studies have shown that NS and TQ may be used for the treatment of diabetes-induced osteoporosis and for the promotion of fracture healing. The mechanism involved is unclear, but it was postulated that the antioxidative, and anti-inflammatory activities may play some roles in the treatment of osteoporosis as this bone disease has been linked to oxidative stress and inflammation. This paper highlights studies on the antiosteoporotic effects of NS and TQ, the mechanisms behind these effects and their safety profiles. NS and TQ were shown to inhibit inflammatory cytokines such as interleukin-1 and 6 and the transcription factor, nuclear factor κB. NS and TQ were found to be safe at the current dosage for supplementation in human with precautions in children and pregnant women. Both NS and TQ have shown potential as antiosteoporotic agent but more animal and clinical studies are required to further assess their antiosteoporotic efficacies.
A major concern of cancer chemotherapy is the side effects caused by the non-specific targeting of both normal and cancerous cells by therapeutic drugs. Much emphasis has been placed on discovering new compounds that target tumour cells more efficiently and selectively with minimal toxic effects on normal cells.
The cytotoxic effect of thymoquinone, a component derived from the plant Nigella sativa, was tested on human glioblastoma and normal cells. Our findings demonstrated that glioblastoma cells were more sensitive to thymoquinone-induced antiproliferative effects. Thymoquinone induced DNA damage, cell cycle arrest and apoptosis in the glioblastoma cells. It was also observed that thymoquinone facilitated telomere attrition by inhibiting the activity of telomerase. In addition to these, we investigated the role of DNA-PKcs on thymoquinone mediated changes in telomere length. Telomeres in glioblastoma cells with DNA-PKcs were more sensitive to thymoquinone mediated effects as compared to those cells deficient in DNA-PKcs.
Our results indicate that thymoquinone induces DNA damage, telomere attrition by inhibiting telomerase and cell death in glioblastoma cells. Telomere shortening was found to be dependent on the status of DNA-PKcs. Collectively, these data suggest that thymoquinone could be useful as a potential chemotherapeutic agent in the management for brain tumours.
Hepatocellular carcinoma accounts for about 80–90% of all liver cancer and is the fourth most common cause of cancer mortality. Although there are many strategies for the treatment of liver cancer, chemoprevention seems to be the best strategy for lowering the incidence of this disease. Therefore, this study has been initiated to investigate whether thymoquinone (TQ), Nigella sativa derived-compound with strong antioxidant properties, supplementation could prevent initiation of hepatocarcinogenesis-induced by diethylnitrosamine (DENA), a potent initiator and hepatocarcinogen, in rats. Male Wistar albino rats were divided into four groups. Rats of Group 1 received a single intraperitoneal (I.P.) injection of normal saline. Animals in Group 2 were given TQ (4 mg/kg/day) in drinking water for 7 consecutive days. Rats of Group 3 were injected with a single dose of DENA (200 mg/kg, I.P.). Animals in Group 4 were received TQ and DENA. DENA significantly increased alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, thiobarbituric acid reactive substances (TBARS) and total nitrate/nitrite (NOx) and decreased reduced glutathione (GSH), glutathione peroxidase (GSHPx), glutathione-s-transferase (GST) and catalase (CAT) activity in liver tissues. Moreover, DENA decreased gene expression of GSHPx, GST and CAT and caused severe histopathological lesions in liver tissue. Interestingly, TQ supplementation completely reversed the biochemical and histopathological changes induced by DENA to the control values. In conclusion, data from this study suggest that: (1) decreased mRNA expression of GSHPx, CAT and GST during DENA-induced initiation of hepatic carcinogenesis, (2) TQ supplementation prevents the development of DENA-induced initiation of liver cancer by decreasing oxidative stress and preserving both the activity and mRNA expression of antioxidant enzymes.
diethylnitrosamine; thymoquinone; hepatic carcinogenesis; gene expression
Thymoquinone (TQ), the major active component of the medicinal herb Nigella sativa Linn., has been described as a chemopreventive and chemotherapeutic compound.
In this study, we investigated the effect of TQ on survival, actin cytoskeletal reorganization, proliferation and signal transduction in multiple myeloma (MM) cells.
We found that TQ induces growth arrest in both MDN and XG2 cells in a dose- and time-dependent manner. TQ also inhibited CXC ligand-12 (CXCL-12)-mediated actin polymerization and cellular proliferation, as shown by flow cytometry. The signal transducer and activator of transcription (STAT) and B-cell lymphoma-2 (Bcl-2) signaling pathways may play important roles in the malignant transformation of a number of human malignancies. The constitutive activation of the STAT3 and Bcl-2 pathways is frequently observed in several cancer cell lines, including MM cells. Using flow cytometry, we found that TQ markedly decreased STAT3 phosphorylation and Bcl-2 and Bcl-XL expression without modulating STAT5 phosphorylation in MM cells. Using western blotting, we confirmed the inhibitory effect of TQ on STAT3 phosphorylation and Bcl-2 and Bcl-XL expression.
Taken together, our data suggests that TQ could potentially be applied toward the treatment of MM and other malignancies.
Cytoskeleton; multiple myeloma; proliferation; signaling; thymoquinone