Suppression of penicillin-induced epileptiform activity by Nigella sativa: Possible mediation by neurotransmitters

To investigate the effects of whole body vibration on the central nervous system, rats were exposed to various whole body vibrations and examined for changes in the levels of norepinephrine (NE) in whole brain or regions of the brain. Whole brain NE had decreased significantly (P less than 0.05) after an acceleration of 5.0G with a frequency of 20 Hz; and the decrease was also observed in the hypothalamus (P less than 0.01) and the hippocampus (P less than 0.10). Exposure to noise [100 dB (A)] caused a significant decrease in NE. This decrease related particularly to a significant decrease in midbrain NE (P less than 0.05) and a non-significant decrease of NE in the hypothalamus.

Effect of chronic treatment of aqueous extract root extract of Moringa oleifera (350 mg/kg) on penicillin-induced convulsion and the changes of EEG pattern and brain serotonin (5-HT), dopamine (DA) and norepinephrine (NE) level were studied in Holtzman strain adult albino rats of both sexes. The results revealed that pretreatment with Moringa oleifera (MO) inhibited penicillin-induced seizure and decreased the number and duration of spike wave discharges. Moringa oleifera significantly increased the NE level in cerebral cortex (CC) and midbrain (MB) and decreased that in the cerebellum (CB). Similarly, dopamine level significantly increased in MB and CB and decreased in CC and caudate nucleus (CN) and 5-HT level significantly increased in all four brain regions. Thus Moringa oleifera suppresses penicillin-induced epileptic seizure by changing the electrical activity and by altering the 5-HT, norepinephrine and dopamine balance.

This study was conducted to determine the inhibitory dose of the hot and cold aqueous extracts of Pimpinella anisum (PA) , Foeniculum vulgara (FV) , and agroup of different medical herbs on growth of bacteria , Staphylococcus aureus isolated from the sputum of bronchiolitis patients . Minimum Inhibitory concentration (MIC) method was used to test the sensitivity of the bacteria toward the above extract . The hot aqueous extract of (PA)in concentration of 23.8 and 28mg/ ml gave a strong inhibitory ability on the growth of the bacteria at MIC 0.01 mg/ ml compared with the highest concentration of 47.6 mg/ml which did not inhibit the bacterial growth at MIC 0.02 mg/ml . The cold aqueous extract of PA at 125 mg /ml concentration also did not inhibit the bacterial growth up to MIC 0.12 mg / ml . This study also revealed that a concentration of 17.12 mg / ml of hot aqueous extract of FV seeds had no inhibitory effect on growth up to MIC 0.008 mg / ml . The combined hot aqueous extract of PA and FV seeds in a ratio of 1gm to 0.5 gm respectively an 1gm to 1 gm (24and 40.32mg / ml respectively ) also did not have any inhibitory effect of bacterial growth up to MIC 0.002 and 0.004 mg / ml, respectively . The results of this experiment also revealed that hot aqueous extract of similar quantities and concentrations ( 17.28 and 31.74 mg /ml ) of a mixture of several medical herbs like ( PA , FV , Anthemis nobilis , Thymus bovei ,Gum Arabic, Nigella sativa , Althaea , and Cydonia vulgaris ) did not show any inhibitory action on bacterial growth up to MIC of 0.004 and 0.007 mg / ml . It could be concluded that the inhibitory ability of the hot aqueous extract of PA seeds is the best compared to the other extracts used . The inhibition of bacterial growth may need a carefully selected medical herbs in different concentrations and combination .

Diabetes mellitus (DM) is the most common metabolic disease worldwide. Multiple medications and side effects, the most significant and prevalent themes in diabetes mellitus ultimately determine novel directions and avenues in drug discovery. The objective of this study was to determine the effects of NS (Nigella sativa) L. Seed hydroalcholic Extract on hypoglycemic and hypolipidemic condition in Streptozotocin- induced diabetic rats. DM was induced by single intraperitoneal injection of freshly prepared Streptozotocin (STZ) (65 mg/kg body weight) solution. Mice were divided into six groups. This study was conducted for 28 days and blood glucose level was measured at 7 days interval. Hyperlipidemic was induced by mixture of cholesterol (1.5%) and cholic acid (0.5%) with diet of rats. At the end of the treatment, the blood glucose level and lipid profile was measured by using commercial kits. It was observed that NS (Nigella sativa) has a potential hypoglycemic effect as it significantly (p<0.001) decrease blood glucose level compared to diabetic group. The SGPT, SGOT and CRP were also decreased significantly (p<0.05). Therefore NS (Nigella sativa) might be effective against liver malfunction. An indicative antilipidemic effect was also observed as TC, TG, LDL, VLDL showed significant (p<0.05) decrease whereas HDL showed significant increase (p<0.001) by NS (Nigella sativa) treatment compared to diabetic group. These results showed that hydroalcholic extract of NS (Nigella sativa) at low doses has hypoglycemic effect and as well as lipid profile in diabetic subjects. Nigella sativa is a potential protective natural agent against atherosclerosis, hepatoprotective and cardiovascular complication in diabetes rats.

Grape seed extracts (GSE) are very potent antioxidant and exhibit numerous interesting pharmacologic activities, including an antioxidant property, and has been suggested to be of use in treatment of several diseases. The present study has been undertaken to investigate the protective and therapeutic effect of GSE against lead-induced neuro and hepatotoxicity in rat. Male albino rats were divided into six groups: the 1st group, rats were injected daily with saline vehicle and served as negative control, the 2nd group (positive control group), the rats were injected (i.p.) with subacute dose (100 mg/kg b·w/day) of lead acetate (LA). The 3rd group (protective group), the rats were injected (i.p.) with LA (100 mg/kg b·w/day) for 7 days after treatment with GSE (100 mg/kg b·w/day) for 3 weeks. The 4th, 5th and 6th groups (therapeutics groups), rats were injected (i.p.) with subacut dose (100 mg/kg b·w/day) of lead acetate for 7 days, then treated with GSE (100 mg/kg b·w/day) for one, two and three weeks, respectively. The level of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and 5-hydroxyindol acetic acid (5-HIAA) were evaluated in brain regions (cerebellum, brainstem, striatum, cerebral cortex, hypothalamus and hippocampus). The result indicated that the administration of subacute dose of LA (100 mg/kg/day, i.p.) induce a significant decrease in NE, DA, 5-HT and 5-HIAA content in all tested brain regions. Also the obtained data showed significant increase in liver enzymes: serum glutamate oxaloacetate transaminase (GOT), serum glutamate pyruvate transaminase (GPT) and Lactate dehydrogenase (LDH) level in group 2 (positive control). There is an improvement in neurotransmitters content. Also the obtained data showed significant in- crease in liver enzymes of protective (G3) and therapeutics groups (G4, G5 and G6) which received GSE compared with animal group that received lead acetate (G2). This is may be the presence of proanthocyanidins and procyanidins which have antioxidant and free radical scavenging activities. The result suggests that grape seed extract may prevent lead-induced neurotoxicity and hepatotoxicity.

DNA Methylation Signatures within the Human Brain

Background: Picralima nitida is a West African plant with varied applications in African folk medicine. Aqueous extract of seeds of Picralima nitida was used to evaluate its protective effect on dexamethasone-induced insulin-resistance in rats. Methods and Findings: Male rats were divided into five groups for acute and subacute study. At the end of the acute study, Oral Glucose Tolerance Test was performed. For the subacute study, Groups 1 and 2 received distilled water for 11 days orally and from day 7, either saline or dexamethasone (8 mg/kg) intraperitoneally for the last 5 days. Groups 3, 4 and 5 were respectively pretreated with glibenclamide (10 mg/kg), P. nitida extract at the doses of 200 mg/kg or 400 mg/kg orally for 11 days. At the end of the experiment on day 12, blood was collected for biochemical analysis and the animals were subjected to a fasting glucose test and then thereafter sacrificed. The liver, pancreas, kidney, and adrenal were weighed and histological analysis performed. The Area Under the Curve (AUC) of the glucose tolerance test, performed 4 hours after the end of acute treatment at a dose of 400 mg/kg of the extract, was significantly reduced (p<0.01). In subacute treatment, the AUC of the aqueous extract of the seeds of Picralima nitida was significantly reduced at doses of 200 mg/kg and 400 mg/kg compared to rats treated with dexamethasone. Furthermore, there was a significant decrease in Total Cholesterol and LDL-Cholesterol with the extract treatment as well as with glibenclamide which decrease Total Cholesterol. Glibenclamide and the extract at 400 mg/kg prevented the drop in protein levels induced by dexamethasone. Adrenal atrophy was noted in all rats given dexamethasone, as well as increased liver and kidney weights. The pretreatment with the aqueous extract of the seeds of Picralima nitida prevented cytolysis and degeneration of hepatocyte, hypotrophy of the pancreatic islets and tubular and glomerular degeneration caused by dexamethasone. Conclusions: This study reveals that the aqueous extract of the seeds of Picralima nitida has anti-hyperglycemic and antihypercholesterolemic properties that may justify its use in traditional medicine against diabetes abnormalities.

Obesity is a chronic inflammatory disease that represents a risk factor for number of diseases including diabetes, steatohepatitis, and cancer. Using safe natural compounds to ameliorate obesity and its related metabolic syndrome is an interesting spot for research. We investigated the regulatory role and the underlying mechanism of black seed oil (BSO) on high-fat diet (HFD)-induced obesity in rats. The study included two models: the first one aimed to study the prophylactic effect of BSO (BSO administration for 10weeks along with HFD) while the second one aimed to study the treatment role of BSO (BSO administration starting from the 10th week for 4weeks along with HFD). BSO significantly decreased insulin resistance and body weight characteristics in both models. It also normalized lipid profile. Moreover, histopathological examination confirmed these results as BSO significantly decreased adipocyte size and hepatic lipid deposition. Besides, BSO alleviated HFD-induced oxidative stress as indicated by significant increase in the total antioxidant capacity and significant decrease in liver malondialdehyde. Moreover, BSO decreased significantly liver gluconeogenic enzymes mRNA expressions (phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) and increased significantly heme oxygenase-1 (HO-1), nuclear factor erythroid-2-related factor-2 (Nrf2) and insulin receptor mRNA expressions. In conclusion, BSO represents a natural therapy that has the ability to prevent and treat HFD-induced obesity in rats that may be mediated through Nrf2/HO-1 pathway's activation and insulin receptor expression's increase. To our best knowledge, this study represents a novel study that investigates the regulatory role of BSO on Nrf2 pathway in preventing and treating HFD-induced obesity. PRACTICAL APPLICATIONS: Black seed oil is a natural available safe supplement, thus it can be used for prevention from obesity and even treatment of obesity and obesity related complications. Introducing of black seed oil in the treatment regimen of obese patients may be promising.

The effects of dietary lipids on the content and release of norepinephrine and on the overflow of norepinephrine after alpha-adrenoceptor blockade with phentolamine were investigated in isolated perfused rat hearts. Pregnant rats were fed Purina Rodent Chow (reference diet) or a semisynthetic diet containing 16% (wt/wt) of either coconut oil (saturated fatty acids) or sunflower oil (unsaturated fatty acids). Neonatal pups were exposed to the diet via maternal milk and weaned rats were maintained on the same dietary lipid supplementation. Coconut oil caused a significant decrease in cardiac norepinephrine in all age groups when compared with the reference diet (p less than 0.01). Sunflower oil caused a significant increase in cardiac norepinephrine at 14 and 21 days of age when compared with coconut oil (p less than 0.05). Hearts prelabeled with [3H]norepinephrine were stimulated with supramaximal voltage (5 Hz, 2 ms duration, 300 pulses). At 14 and 21 days, coconut oil caused a significant decrease in norepinephrine release when compared with sunflower oil (p less than 0.05). The release of norepinephrine from hearts exposed to sunflower oil diet and the reference diet were comparable. These alterations in neuronal storage and exocytotic release of norepinephrine may be due to dietary-induced membrane perturbations. Phentolamine (10(-8)-10(-6) M) caused a dose-related increase in norepinephrine release following stimulation (supramaximal voltage 2.5 Hz, 150 pulses) of adult rat hearts from all dietary groups. However, the increase above control values was highest for coconut oil and lowest for sunflower oil (p less than 0.01), suggesting changes in receptor sensitivity. It appears that dietary lipid supplementation in the developing and adult rat could affect the myocardial alpha-adrenoceptor microenvironment which could cause changes in the prejunctional alpha-adrenoceptor neuronal function.

Experimental hydrocephalus was induced in rabbits by intracisternal injection of kaolin suspension, and the concentration of noradrenaline (NA), dopamine (DA), and their metabolites was determined in several brain regions. The NA concentration had decreased in the cerebellum, hypothalamus, and pons plus medulla oblongata, and increased in the caudate nucleus at 2 days after kaolin injection (the stage of early intracranial hypertension). At 1 week (the stage of progressive hydrocephalus), the NA content had returned to control levels in all brain regions studied, and it decreased again at 4 weeks (the stage of chronic hydrocephalus) in the pons plus medulla oblongata. The DA level was unchanged throughout the 4-week period after kaolin injection. The concentration of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MOPEG-SO4), the major metabolite of NA, was elevated in all brian regions except the caudate nucleus at all stages after kaolin injection. An increase in MOPEG-SO4 in the caudate nucleus was also observed 1 week after kaolin injection. The content of homovanillic acid (HVA), the major metabolite of DA in the rabbit brain, was decreased in the cerebral cortex at 2 days and at 1 week after kaolin injection, and in the caudate nucleus at 2 days and at 1 week, and 4 weeks. The level of HVA was increased in the hypothalamus at 2 days, in the cerebellum at 2 days and at 1 week, in the pons plus medulla oblongata at 2 days, 1 week, and 4 weeks, and in the midbrain at 4 weeks. These data suggest that, in experimental hydrocephalus in the rabbit, NA release is increased throughout the brain, while DA release is decreased in the cerebral cortex and caudate nucleus, and increased in the cerebellum, hypothalamus, midbrain, and pons plus medulla oblongata.

Background: In folklore, Nigella sativa and Moringa oleifera seeds have long been associated with multifaceted antimicrobial properties, although without extensive empirical scientific validation. Natural products of plant origin have been recognized as potential sources of antimicrobial agents. The antibacterial activity of Moringa oleifera and Nigella sativa against clinical isolates of Staphylococcus aureus has been previously reported in contexts other than burn infections. Objective: This study aimed to compare the antimicrobial effects of Nigella sativa seed and Moringa oleifera seed extracts with gentamicin against Staphylococcus aureus isolates from burn wound infections. The investigation was inspired by ethnobotanical surveys, ethnopharmacological records, and traditional medicinal claims regarding the therapeutic potential of these plants. Materials and Methods: Staphylococcus aureus isolates from burn wound infections were exposed to varying concentrations of Moringa oleifera and Nigella sativa seed extracts (5 µg/mL, 2.5 µg/mL, and 1.25 µg/mL), prepared via cold maceration. Gentamicin at 5 µg/mL served as the standard antibiotic control. All preparations were incubated at 37°C for 24 hours, and antimicrobial activity was assessed by measuring the zone of growth inhibition. Results: Both aqueous and methanol extracts of Moringa oleifera and Nigella sativa seeds demonstrated anti-staphylococcal activity at concentrations ranging from 5 µg/mL to 1.25 µg/mL, particularly at dilution factors of 1:2 to 1:4. However, antimicrobial activity diminished at higher dilutions (1:16 and 1:32). Notably, Nigella sativa seed extract exhibited more pronounced anti-staphylococcal effects than Moringa oleifera. Gentamicin, a broad-spectrum aminoglycoside antibiotic, displayed 100% anti-staphylococcal activity at all tested dilutions. Conclusion: Methanol extracts of Moringa oleifera and Nigella sativa seeds exhibit promising anti-staphylococcal activity and may hold potential for clinical applications as alternative therapies. Gentamicin remains a highly effective standard treatment for Staphylococcus aureus infections, including those associated with burn wounds.

Background: Dental infections were caused by the bacterium overgrowth on the surface of the tooth, and treatment should always be set up to prevent this development.Antibiotics have long been used as a conventional antibacterial medication, but their overuse has resulted in microbes gaining resistance to many of the antibiotics, trying to make many commercialized therapeutic remedies ineffectual and resulting to infection recurrence. In this regard we aim to analyze the antibacterial activity of nigella sativa seeds’ and fenugreek seed extract rinses against S. mutans' colonies.&#x0D; Methodology: It was a preclinical experimental study conducted at Baqai Medical and Dental College Karachi., from January - June 2021. Calculated sample size was n = 80 Consecutive sampling technique was used. Plaque of study participants was collected on sterile strips that was transported to laboratory for culture in sterile containers.The extract of Fenugreek seed and nigella sativa seed was kept in an airtight bottle and stored in a refrigerator till usage. The extracts were diluted in distilled water in 1:4 (Extract: Distilled water). Study participants were instructed to not brush their teeth before sampling. Study participants were divided into four groups (negative control, positive control, fenugreek seed extract group and Nigella sativa group) each group had 20 participants. Diluted Fenugreek seed extract and Nigella sativa extract was given to experimental groups for rinses.&#x0D; Results: There was significant decrease in number of colonies in positive controls, fenugreek seed extract group and nigella sativa extract group and there was no change in number of colonies in control group. Furthermore, the analysis showed significant (p-value = 0.001) difference among the groups followed by post hoc analysis. Post hoc analysis showed no difference between positive control, fenugreek seed extract group and nigella sativa group.&#x0D; Conclusion: Fenugreek seed extract and Nigella Sativa seed extract showed comparable antibacterial properties. Also, the effect was found to be similar to commercially available mouth rinse.

Background: Bisphenol A (BPA), an estrogenic compound, is one of the world’s highest production volume chemicals used in polycarbonate plastics in many consumer products and epoxy resins lining food containers. BPA is known to have toxic effects on various systems in man and animals. The aim of this study was to evaluate the cytogenetic and biochemical changes induced by BPA on testis of albino rats and the possible protective effect of black seed oil. Materials and Methods: This study was carried out on (80 rats), divided into four groups (20 rats each). Group I: negative control Group II: received black seed oil (2ml/ kg b w), Group III: administered BPA (25mg/ kg b w), Group IV: administered BPA + black seed oil same as previous doses. Blood, testis and epididymis were collected for biochemical and cytogenetic evaluation. Results: BPA caused a significant decrease in sperm count, total content of DNA, RNA and Protein in the testis, while, significant increase of DNA damage of spermatocyte, head and tail abnormalities compared with control. Co-administration of BPA+ black seed oil resulted in significant improvement of sperm count, total content of DNA, RNA and Protein with significant decrease in DNA damage of spermatocyte and head and tail abnormalities compared to BPA group. Also, BPA group showed a significant decrease in serum testosterone and catalase levels, while, a significant increased super oxide dismutase (SOD) compared to control. However, BPA + black seed oil group showed significant improvement of serum testosterone, catalase and (SOD) levels compared to BPA group. Conclusion: Exposure of rats to BPA resulted in reproductive toxicity through inducing a significant DNA damage and impaired synthesis of DNA, RNA and protein in testicular tissue. Black seed oil attenuate oxidative damage in rat testis via upregulating the activities of enzymatic antioxidants Catalase and SOD.

Background and aim of the study: DM represents an important independent risk factor for the development of and mortality from coronary heart disease (CHD), increasing the risk by 2 to 4 times. According to WHO data, more than 75% of patients with DM die due to vascular accidents. This study investigated the effects of some plants used in Saudi Arabia and some other Arab countries as antidiabetic agents and explores its metabolic effects. Material and Methods: One hundred fifty adult male Albino Rats were divided into six experimental groups each consist of twenty five rats. The first group was considered as a control group. The rest of groups were affected by induction of experimental diabetes by subcutaneous injection of Alloxan. The second group consisted of diabetic rats without any treatment. The third group was treated by the aqueous extract of mixture contains Foenugreek, Nigella sativa and Termis seeds. The fourth group was treated with the aqueous extract of Nigella sativa seeds (100 mg / kg of body weight), while the fifth group was treated with the aqueous extract of Foenugreek seeds (100 mg / kg of body weight). The sixth one was treated with the aqueous extract of Termis seeds (100 mg/kg body weight). After four weeks of treatment, different biochemical parameters were performed including estimation of blood sugar level and serum insulin level. Pancreatic and liver samples were obtained and processed for microscopic and quantitative evaluation after staining the prepared sections with both Heamatoxylin and Eosin as well as special stain for demonstration of the different pancreatic cells in the Islet of the Langerhans. Results: The usage of the mixture or each plant alone corrected the glucose level and insulin level. Microscopically there was definite decrease in the number and diameter of beta pancreatic cells in the diabetic group while the other pancreatic cells were not affected (alpha and delta cells). The use of medicinal plants in the different groups of this study greatly improved such cellular changes and the level of blood sugar level was corrected. Also, improve dyslipidemia present in diabetic rats. The results showed that the activity of the mixture was better when compared with Nigella, Foenugreek or Termis seeds alone. Conclusions: The water extract of the mixture is the most powerful in amelioration hyperglycemia and most of all damage effects of Alloxan on hematological parameters and lipid profile. Also, it can control most of the metabolic risk factors of CAD in diabetic rats. So it is advised to use the plant mixture as an antidiabetic agent rather than the use of each plant separately. Repeating such study with the use of variable doses may be helpful in better evaluation for the required dose.

Aim: This study was carried out to determine the Phytochemical contents of Azadirachta indica seed and Nigella. sativa and their synergistic therapeutic effect on indices of clinical importance in malaria-induced male wistar rats.&#x0D; Study Design: The animals that were used for this study where divided into 4 groups of 6 rats each. All rats in the 3 test groups were inoculated with 0.2 ml blood parasitized with Plasmodium falciparum and observed for 3 days for manifestation of signs of malaria. Treatment with Azadirachta indica seed extract only, Nigella sativa extract only and a combination of Azadirachta indica seed and Nigella sativa extracts was conducted for a period of 14 days. Changes in weight of the rats and hematological parameters RBC, WBC,PCV and Hemoglobin were assessed before commencement of treatment and through the 14 day period.&#x0D; Place and Duration of Study: This study was conducted at the National Veterinary Research Institute (NVRI), Vom in collaboration with the Department of Biological Sciences Abubakar Tafawa Balewa University, Bauchi, Nigeria between March 2022 and May 2022. &#x0D; Methodology: Azadirachta indica seed and Nigella sativa seeds were extracted with distilled water and the lethal doses (LD₅₀) were determined on the rats. Qualitative phytochemical screening of Azadirachta indica seed and Nigella sativa extracts was performed. Plasmodium infected rats were divided into 3 groups of 6 rats each and a normal control group which was left uninfected. Symptoms of malaria infection were observed three days after infection. The treatment was commenced on day 4 post-infection and was continued for a period of 14 days. Each plant extract and the mixture of both extracts were administered at 100, 200, and 300mg/kg body weight of the rats. After first 4 days, 7 days, and at 14 days of treatment each rat’s blood sample was taken for hematological analysis.&#x0D; Results: The plant extracts lethal dose (LD₅₀) was considered safe for Azadirachta indica seed at 5000mg/kg and 2000mg/kg for Nigella sativa respectively. Qualitative phytochemical screening revealed the presence of saponins, alkaloids, flavonoids, resins, glycosides, steroids in both Azadirachta indica seed extract and Nigella. sativa extract. Treatment with a mixture of both extracts showed a high restoration of red blood cell count with a significant (p&gt;0.05) increase in RBC with a non-significant decrease in PCV and WBC. There was no significant decrease in hemoglobin concentration observed across all treatment groups at the end of the 14 day study.&#x0D; Conclusion; The combination of both Azadirachta indica seed and Nigella sativa is well tolerated and safe for Plasmodium parasites effects on wistar rats at concentration of 400mg/kg of body weight which showed highest values of restoration of RBC count as compared to the normal control group. Group A treated with only Nigella sativa also showed RBC count higher than that obtained in group B treated with only Azadirachta indica seed. PCV values compared with the normal control group showed an 8% increase at concentration of 400mg/kg at the end of the experiment in group C treated with the mixture of Azadirachta indica seed and Nigella sativa. At 200mg/kg concentration, the mixture of Azadirachta indica seed and Nigella. sativa gave a 25% increase in PCV values. This shows that the synergistic effect of Azadirachta indica seed and Nigella sativa has better therapeutic effects against Plasmodium parasites than either Nigella sativa or Azadirachta indica seed as a single therapy. This study provides a basis for the development of a cheaper plant-based antimalarial combination therapy.