An efficient solvent-free synthesis of a 10-member library of octanoyl linked substituted aryl thioureas was accomplished successfully. The octanoyl isothiocyanate was freshly prepared in excellent yield and purity by the reaction of potassium thiocyanate with octanoyl chloride followed by removal of potassium chloride by filtration. The reaction of the latter with a series of ten different substituted anilines by stirring at 60-65 degrees C lead to the formation of the title compounds. The in vitro antifungal activity of newly synthesized compounds was evaluated against Aspergillus niger, A. flavus and Fusarium solani strains of pathogenic fungi. Antibacterial assay was carried out against Gram positive (Staphylococcus aureus, Micrococcus luteus) and Gram negative bacterial strains (Escherichia coli, Enterobacter aerogens). Furthermore, anti-oxidant potential and enzyme inhibition studies against alpha-amylase and butyryl cholinestrase were performed. The results obtained indicated moderate to excellent activities of most of the compounds whilst some derivatives showed potency higher than the standard used.
Quantification of cell viability and proliferation form the fundamental for numerous in vitro assays in response to external factors. An MTT assay is a colorimetric assay based on assessing the cell metabolic activity. A549 Lung adenocarcinoma cell line was used to see the cytotoxic potential of a new drug for initial screening of apoptosis or necrosis. The biochemical mechanism behind the MTT assay involves NAD(P) H-dependent cellular oxidoreductase enzyme that converts the yellow tetrazolium MTT [3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide] into insoluble (E,Z)-5-(4,5-dimethylthiazol-2-yl)1,3-diphenylformazan (formazan). The formed formazan can be dissolved with dimethyl sulfoxide (DMSO) to give a purple color with characteristic absorption at 540 nm. Intensity of purple color is directly proportional to the cell number and thus indicating the cell viability.
The aim of this study was to investigate the antidepressant effects of grape seed oil in male mice (n=60) using tail suspension and forced swim tests. Mice were divided to six groups of 10 in each group. Group I: Intraperitoneally receiving normal saline; Group II: Received normal saline & stress; Group IIIV: Injected (i.p.) with different (60, 120, and 240 mg/kg) doses of grape seed oil; and Group VI: Received fluoxetine (10 mg/kg). Grape seed oil in 60 mg/kg significantly decreased immobility time in tail suspension and forced swim tests under chronic unpredictable stress compared to groups under chronic stress receiving normal saline and grape seed oil (120 and 240 mg/kg). Grape seed oil (60 mg/kg) significantly improved the motor balance in mice under chronic stress. It had no significant effect on serum corticosterone level. Grape seed oil can improve depression symptoms in mice.
The antifungal, anti-yeast and anti-oxidant effects of Calamus aromaticus leaves were studied. The extract showed mild activity against two fungal strains and strong activity against the yeast. The results also indicated the presence of extremely high DPPH radical scavenging potential in all tested samples at each of the seven concentrations used. The data further revealed that ethyl acetate and n-butanol extracted samples measured highest antifungal (25.0% inhibition each against Rhizopus oryzae at 1000 µg/well), anti-yeast (73.5 and 66.4% activity respectively at 2000 µg/disc) and anti-oxidant (96.6 and 97.7% activity respectively at 250 ppm) potential while samples extracted with water were least potent. HPLC analysis of the extracted samples confirmed ethyl acetate and n-butanol as the solvents of choice for the extraction of antifungal, anti-yeast and anti-oxidant compounds (phenolics) from the leaves of C. aromaticus.
The present study investigates antimicrobial and anti-oxidant potential of different solvent extracted samples from Periploca hydaspidis through disc diffusion assay. Pseudomonas aeruginosa and E. coli were sensitive to crude extracts and all fractions measuring varying degree of growth inhibition. Similarly, the growth of Citrobacter freundii was not inhibited by crude methanolic extracts, n-hexane, ethyl acetate and aqueous extracted samples. Maximum growth inhibition was measured against Klebsiella pneumoniae exposed to aqueous fraction followed by n-hexane fraction. Our results also suggested that among various fungi, Candida albicans was sensitive to crude methanolic extracts, n-hexane and aqueous fractions compared with other fractions. The rest of the fungi under test were resistant to crude and all fractions showing no zone of inhibition. All the extracted samples of the stems and roots showed antioxidant activity, however, crude methanolic extract of stem tissues exhibited better antioxidant activity than the other extracts.
The presents study investigates the effect of ludartin on spinal cord injury in rat model. Ludartin treatment decreased the expression of myeloperoxidase and malondialdehyde in spinal cord tissues. The expression of glutathione and superoxide dismutase were enhanced. It also exhibited inhibitory effect on reduction of NeuN-positive cells. The proportion of TUNEL positive cells was also regulated. In addition, ludartin treatment prevented the onset of apoptosis which was evident by decrease in caspase-3 and Bax level and increase of Bcl-2 level. Up-regulation of tumor necrosis factor-alpha, interleukin-1 beta and I interleukin-6 by spinal cord injury was suppressed by ludartin treatment. There was improvement in locomotion of rats by treatment with ludartin. Ludartin treatment of spinal cord injury rats improves locomotion by inhibiting inflammatory cytokine expression and preventing cell apoptosis. Thus, ludartin has therapeutic importance in spinal cord injury treatment.
The present study aims to assess the anxiolytic and hypnotic activity of ethanolic extract of Cocculus laurifolius leaf in mice. Anxiolytic activity was observed using behavioral paradigms while hypnotic activity was assessed by sodium pentobarbital induced hypnosis in mice. Animals were treated with the extract at dose 200 and 400 mg/kg orally for 30 days. Anxiolytic and hypnotic effect were observed on day 1, 7, 15 and 30 of treatment. Significant increase in the number of entries and time spent in open arm were observed in elevated plus maze. Similar results were observed in light/dark, open field and hole board test. The anxiolytic effect was substantially greater at dose 200 mg/kg in comparison to dose 400 mg/kg. Minimal hypnotic activity was observed with decrease in onset and prolongation in duration of sleep at dose 400 mg/kg, while dose 200 mg/kg did not produce any hypnotic effect. These results showed that the ethanolic extract of C. laurifolius leaf might have potential anxiolytic and hypnotic activity in mice.
The aim of this study is to investigate the antidepressant effects of Mentha pulegium essential oil in BALB/c mice. Six experimental groups (7 mice each) were used. Forced swim test was performed 30 min after essential oil injection. In the groups receiving M. pulegium essential oil (50, 75 and 100 mg/kg), immobility duration significantly decreased compared to the control group. M. pulegium (50 and 75 mg/kg) resulted in significant decrease in nitrate/nitrite content in serum compared to the control group. M. pulegium essential oil antidepressant effect that may be due to the inhibition of oxidative stress. The results showed that decrease in nitrate/nitrite content in serum and high anti-oxidant effects of M. pulegium essential oil.
The purpose of this study was to investigate the effect of hydroalcoholic extract of Artemisia persica (100, 200 and 400 mg/kg) on pentylenetetrazole induced seizure and memory impairment. Sixty mice were assigned to seven groups. Pentylenetetrazole (35 mg/kg) was injected at 48 hours intervals for 9 days, and at 60 mg/kg on day 10 to induce seizure model. Different doses of A. persica extract were injected daily 30 min before pentylenetetrazole injection. Exposure of mice to extract significantly reduced the frequency of repeated spinning and jumping and tonic seizures in seizure model. In addition, the extract significantly reduced the increased levels of malondialdehyde in serum and brain. The extract significantly increased the serum and brain anti-oxidant capacity but had no significant effect on nitric oxide. The extract (100 mg/kg) significantly improved pentylenetetrazole induced memory impairment. The hydro-alcoholic extract of A. persica has a protective effect against pentylenetrazole-induced seizure.
The objective of the present study was to evaluate the efficacy and safety of regorafenib in comparison with dinutuximab with chemotherapy in Chinese children with advanced neuroblastoma. The patients aged less than 16 years who were histologically diagnosed with advanced neuroblastoma were enrolled and randomized to receive either regorafenib plus best supportive care or dinutuximab plus chemotherapy plus best supportive care in a 1:1 ratio. The tumor response assessment was made in accordance with modified international neuroblastoma response criteria. Adverse events were also assessed. Regorafenib showed prolonged overall survival and progression-free survival than who received dinutuximab plus chemotherapy (overall survival: median 32.3 months versus 27.2 months; hazard ratio = 0.45; 95% 0 0.11-0.13, p<0.001; progression-free survival: stratified hazard ratio = 0.48; 95% CI 0.11-0.14; p<0.01). Moreover, the overall response rate was greater in patients treated with regorafenib as compared to dinutuximab group. Regorafenib appears efficacious and has a manageable safety profile in Chinese children with advanced neuroblastoma.
The aim of the present study was to evaluate the effectiveness of e-learning (virtual class) in achieving procedural knowledge necessary to conduct practical class in the laboratory. In this study, teaching modules were prepared on eight selected topic related to pharmacology laboratory works. Virtual classes were conducted among the postgraduate MD students (n=26) of this department. To know the existing procedural knowledge pre-test was taken before the classes and to evaluate the effectiveness of virtual class, a post-test was carried out seven days later. To get the feedback from students, two additional questionnaire surveys were done. The performance of each student improved in the post-test in comparison to the pre-test. Most of the students mentioned that virtual class was easier in comparison to face to face class. But they preferred combination classes to learn procedural knowledge.
The objective of this study was to evaluate the in vitro anti oxidant, hypotensive and the diuretic: activities of Origanum glantiulosum leaves in rat. Chemical analysis revealed the isolation of katuranin and 5-isopropyl-3-methyl phenol. Ethyl acetate extract possessed highest scavenging activity against DPPH and hydroxyl radicals. Intravenous administration of extracts (0.04 to 12 mg/kg body weight) dose-dependently decreased the blood pressure (systolic, diastolic and mean) of the anesthetized rat. Methanol extract showed dose-dependent diuretic activity by increasing the urine output (77%) and the urinary excretion of sodium and potassium. In conclusion, this study supports the use of O. glansulasum in traditional medicine as hypotensive and diuretic agents.
In this study, the effect of different extracts of Centaurea pterocaula were evaluated on 6 mm wound created by punch biopsy on the rat back. The leaves of the plant were powdered and extracted with distilled water, methanol, n-hexane and ethyl acetate. Extracts were obtained in the form of pomade with vaseline and applied topically to the wounds. The wound measurements performed on day 0, 2, 4, 6, 8, 10 and 12 and the histopathological examination performed on day 12. The n-hexane extract had an accelerating effect on wound healing and made a positive contribution to the healing process. In conclusion, C. pterocaula has a promising future for new drug development studies by its wound healing property.
This study aimed to investigate the anti-tumor effect of the compound 34 on MCF-7 cells in vitro and explore its mechanisms. The MTT assay results showed that the compound 34 selectively inhibited the estrogen receptor-positive cells proliferation. Hoechst 33342 staining showed nuclear pyknosis, nuclear debris associated with apoptotic bodies. JC-1 staining showed the loss of mitochondria] membrane potential. Although the compound increased the intracellular reactive oxygen species (ROS), the apoptosis was not prevented by pretreatment with ROS scavengers. The Western blotting showed apoptosis-related protein like cytochrome c, and cleaved PARP protein increased. Furthermore, docking studies exhibited that the compound could hind to ERa. In summary, compound 34 selectively inhibited the estrogen receptor positive cells proliferation and induced apoptosis in MCF-7 cells via ROS-independent intrinsic apoptosis in MCF-7 cells. It may he a potential targeted drug of estrogen receptor for therapeutic application of breast cancer.
The anxiolytic and antidepressant like effects of Salvia officinalis extract (50, 100 and 200 mg/kg) were evaluated using marble burying, forced swimming and open-field tests in intact and hippoczunpal lesioned rats. Additionally, S. officinalis was evaluated on rat's memory using conditioned learning test and we screened the methanolic extract for anti-oxidant activity, phytochemical and high performance liquid chromatography analyses. The administration of sage extract showed a significant reduction of immobility time in lesioned and intact animals during the forced swim test and anxiolytic effect in marble burying test. In the case of conditioned learning paradigm, memory enhancement was observed in sage treated group which indicates a cognition improvement. These activities seem to be related to the anti-oxidant capacity and the phytochemicals (phenolic, flavonoid, and tannin) detected into the extract of S. officinalis. The findings show that the methanolic extract of sage possess antidepressant-like effect, anxiolytic activity and also may contain bioactive compounds that stimulate learning in rat.
Evaluating the effect of herbal extracts has been always interesting for cancer researchers considering that these natural materials could be suitable sources for finding new anti-cancer agents. In the present study, Acroptilon repens methanol extract had been evaluated for its cytotoxic effects in two human breast cancer cell lines, MCF-7 and MDA-MB-468, using MTT assay. The apoptosis potential had also been evaluated using annexin-Wpropidium iodide assay, Hoechst 33258 staining and evaluating the cell cycle with flow cytometery. The MTT results showed cytotoxicity with IC50 values of 69.2 and 32.6 mu g/mL for MCF-7 and MDA-MB-468 cells, respectively. The results of the apoptosis assays confirmed the apoptosis potential of the plant extract in the breast cancer cell lines suggesting A. repens for further cancer studies.
This study was conducted to investigate the neuroprotective effect of Citrus auratium essential oil on hippocampal injury induced by transient global cerebral ischemia and reperfusion in rat. In total 50 rats were randomly assigned into five groups; control, sham, ischemia, and essential oil-treated (50 or 75 mg/kg) rats. Ischemia was induced by occlusion of the carotid artery for 30 min. Spatial memory, passive avoidance learning, anti-oxidant capacity, and lipid peroxidation during ischemia/reperfusion were evaluated. The compounds of the essential oil were analyzed by gas chromatography/mass spectrometry. Induction of ischemia/reperfusion caused a decline in learning and passive avoidance memory in rats. C. aurantium exerted protective effects on the spatial memory, passive avoidance learning, anti-oxidant capacity, and lipid peroxidation during ischemia/reperfusion in animals. The main compounds of the essential oil were camphor (45.9%), thymol (11.2%), linalool (6.6%), carvacrol (6.3%) and borneol (2.9%). The essential oil with anti-oxidant compounds significantly decreased the symptoms of ischemia/reperfusion injury.
Herein the antidepressant-like effect of theallavin-3-gallate, a plant polyphenolic compound in 1-methyl-4-phenyl pyridinium-induced neuronal injury in N2a cells used as an in vitro model of depression as well as in vivo. The results from MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) and lactic dehydrogenase assay revealed that theallavin-3-gallate exerted a neuroprotective effect in N2a cells. Treatments with mixtures of 1-methyl-4-phenyl pyridinium (20 mu M) and four concentration levels of theaflavin-3-gallate increased cell viability from 23.3 to 79.6% while lactic dehydrogenase leakage value decreased from 63.2 to 23.4 U/L. Fura-2-acetoxymethyl ester assay for Ca2+ concentration measurement revealed that different doses of theaflavin-3-gallate or fluoxetine (20 mu M) reduced the intracellular Ca2+ overloading in N2a cells induced by 1-methyl-4-phertyl pyridinium. Inverted phase microscopy showed that theatlavin-3-gallate induced neurite outgrowth in 1-methyl,4-phenyl pyridinium-induced neurotoxicity in N2a cells. Theaflavin-3-gallate could significantly reduce the immobility time of mice in both forced swimming test and tail suspension test.
In a study designed to determine the antibacterial potential of endophytic fungi inhabiting plants of Cyperaceae family, 72 morphologically distinct endophytic fungi were isolated from six plants and their antibacterial activities against two Gram positive and three Gram negative pathogenic bacterial species were examined. Two antibacterial metabolites from two endophytes were also isolated and their chemical structures and minimum inhibitory concentrations were determined. Sixty six fungal extracts (92%) were active against at least one bacterium tested. Butyrolactone I isolated from the Aspergillus terreus and 9-epi viridol isolated from Trichoderma virens exhibited MIC values in the range 128-256 mu g/mL against Gram positive Bacillus subtilits, Staphylococcus aureus, methicillin resistant S. aureus (MRSA) and Escherichia coli. Both compounds were inactive against other microorganisms tested. This study confirmed that Cyperaceae plants harbor numerous endophytes that produce antibacterial metabolites active against both Gram positive and, to a lesser extent, Gram negative bacteria.