جستجوی مقالات مرتبط با کلیدواژه "کومارین" در نشریات گروه "پزشکی"

 The use of functionalized metal nanoparticles against cancer cells has gained assiduous attention. This study aimed to assess the inhibitory activity of iron oxide nanoparticles coated with glucose and conjugated with coumarin (Fe3O4@Glu-Coumarin) on breast cancer cell line, as well as the expression of the caspase-8 and caspase-9 genes.

The physical and chemical properties of nanoparticles were evaluated using FT-IR, XRD, EDS-map, and electron microscope imaging. The toxicity of the synthesized nanoparticles was determined using the MTT assay, and the 50% inhibitory dose (IC50) was calculated. Moreover, the effect of nanoparticles on apoptosis induction was investigated by measuring the expression level of the caspase 8 and 9 genes and flow cytometry analysis. Statistical analyses were performed in SPSS software. One-way analysis of variance (ANOVA) was employed to assess significant differences between nanoparticle-treated and control groups. A p-value of less than 0.05 was regarded as statistically significant.

The synthesis of Fe3O4@Glu-Coumarin nanoparticles was confirmed by physicochemical tests, including FT-IR, XRD, EDS-mapping, and electron microscope imaging. The nanoparticles had dimensions of 25 to 50 nm and contained Fe, O, and C elements. The treatment of MCF-7 cells with nanoparticles caused a significant decrease in the survival of cancer cells, and the IC50 was 93μg/ml. The exposure of cells to the nanoparticles caused a marked increase in the expression of caspases 8 and 9 by 2.6 and 2.9 folds, respectively, compared to the control group. In addition, the frequency of apoptotic cells after treatment with the nanoparticles increased from 2.21% to 84%.

The results of this study pointed out that Fe3O4@Glu-Coumarin increased the expression of the caspases 8 and 9 genes in breast cancer cells and, as a result, can activate the intrinsic and extrinsic apoptotic pathways, thereby inhibiting the proliferation of cancer cells.

Alzheimer's disease is one of the most common causes of loss of mental function, which is generally known as dementia (1) .Alzheimer's disease affects almost two percent of people in developing countries (2). The risk of developing the disease increases with age. Alzheimer's disease and its consequences are the Greatest Health Crisis of the 21st Century. Coumarin and its derivatives are one of the most abundant natural compounds in plants. This compound is a heterocyclic oxygen that is known as the parent chemical structure for a class of phytochemicals naturally found in several plant species. These compounds have been used as anticoagulant, antibacterial, anti-osteoporosis and antiasthmatic (6). Quantitative structure- activity relationship (QSAR) is widely used in drug design processes to improve the therapeutic indicators of designed compounds. QSAR models are mathematical equations written based on the relationship between the chemical structure of compounds and their biological activity (7). These equations use different descriptors; these descriptors are divided into different groups such as structural, geometric, spatial, quantum, and the like and are obtained by experimental and computational methods. Due to the time-consuming and costly experimental methods, computational methods are preferred (8). Density functional theory has been one of the most popular methods of solid-state physics since 1970. Though it was not until 1990, when the considered approximations, in theory, were revised, and a better model for exchange interactions was proposed, it was not considered an exact method in quantum chemistry.

Due to the anti-Alzheimer's property of coumarin and its derivatives, In this research, 44 coumarin derivatives have been selected that were previously synthesized and their experimental activity was measured. All of compounds optimized and their quantum descriptors have been obtained using Gaussian software and computational DFTmethod and basis set 6-31G (d), other descriptors were also determined using Dragon software. At first, using IBMSPSS20 software and stepwise multiple linear regression method, the samples were randomly divided into training series (33 molecules) and prediction series (11 molecules). 75% of the samples were considered training and 25% of them as a test, and this ratio was repeated three times to get the best correlation. The training series was used to create a suitable model, and the prediction series was used to evaluate the model. The most important part of creating an efficient model is the selection of appropriate descriptors. After calculating different descriptors, they are selected as suitable descriptors to build the model. In this study, the stepwise method (SW) was used to select the most appropriate descriptors. In a stepwise method by examining all descriptors, the selection process continues until a model with a high correlation coefficient is obtained. Using the stepwise method from among 95 descriptors, six descriptors were selected as the most suitable and were modeled by the MLR method. After selecting the most suitable descriptors, the relationship between the selected descriptors and the activity of the drug compounds was established by a stepwise incremental method. To check the accuracy and validity of the model, internal and cross-validation methods were used. Internal validation is related to the statistical parameters of the training category, one of these parameters is R or the correlation coefficient. An acceptable equation has a correlation coefficient value greater than 0.6. The reported values ​​for R2 are between 0 and 1. R2=0 means no correlation between the activity and the selected variable, and R2=1 means a very good correlation. Increasing the number of parameters in an equation R2 cannot show the correlation value correctly. For this reason, in an equation with several parameters, R2adj is a more accurate scale for expressing correlation. The closer this value is to one, the stronger the linear relationship between the dependent and independent variable. Cross-validation was used to predict the properties of the compounds that were not included in the new model.

The final evaluation of the model is done by external validation, which indicates how much predictive ability the QSAR model has for the compounds outside the model. For the QSAR equation R2= 0.89665 and R= 0.94691 were obtained. Also, MSE=0.51397 and RMSEP=0.81297 and Q2=0.83216 are a confirmation of the acceptability of the obtained model. The obtained equation shows that the activity of these compounds is related to the negative coefficients of RDF065m, nCbH, Jhetp, which means that by increasing the values of these descriptors, the amount of activity decreases.. On the other hand, the activity of these compounds depends on the positive coefficient of nR=Ct and SPH that means by increasing this value, the activity of these compounds also increases. By placing the effective descriptors, the anti-Alzheimer activity values of these compounds were predicted. The comparison of these values with the obtained experimental activities shows an acceptable correlation between the values of experimental and predicted activity. To investigate how much the increase or decrease of the selected descriptors affects the desired activity, a graph of the average effect of the descriptors has been drawn.The y-axis represents the standardized coefficients, and the x-axis represents the selected descriptor using the SW-MLR method. According to this chart, the Jhetp has the most negative , and the nR=Ct descriptor has the most positive effect. In this chart, the descriptors drawn above the chart mean that the amount of activity increases with increasing the value of the descriptor, and for those drawn at the bottom of the chart, the amount of activity decreases as they increase. The evaluation of the domain of application shows that there is no systematic error in the obtained model, and it also shows the efficiency of the model for predicting behavior in experimental methods.

According to the examination of the results presented above, it can be generally concluded that according to the predicted activity values in Table 3, compounds 36 and 37 have the most activity and compounds 21 and 15 have the least anti-Alzheimer activity. The obtained model helps to design new drugs with more activity in the future based on the factors affecting the activity obtained from the QSAR equation. Since computational methods are faster and more accessible than experimental methods, it can be less predicted the necessary structures to design effective drugs.

In recent years, researchers have considered the anticancer activity coumarins, due to their powerful biological activity and poor toxicity that can neutralize the side effects induced by radiotherapy. The aim of this study was to investigate the cytotoxic effects of coumarin on HT-29 and A549 cancer cells.

In this experimental study, the stoke of coumarin was prepared and then for 1,3, and 5 days at concentrations of5, 10, 15, 20, and 25 μM the cells were treated and evaluated on viability days and morphology of the cells indefinite days. The IC50 concentration of coumarin was calculated using MTT assay in two cell lines. Also, the expression of the involved genes in apoptosis such as Bax, Bad, and Bcl-2 was evaluated by the qRT_PCR method. Data were analyzed by a one-way ANOVA test.

The results showed that coumarin reduced the viability and proliferation of HT-29 and special A549 cells by dose and time significantly (P≤0.001), as well as the viability rate of cells in treated cells on the fifth day, significantly decreased compared to the control group (P <0.05). Morphological changes such as reduced chromatin density, cell turnover were also noticeably observed in the cells. Also, molecular results showed that coumarin could significantly increase the expression of Bax, Bad genes and decrease the expression of Bcl-2 gene expression. That these genetic changes in A549 cells were significantly greater than HT-29.

Coumarin is capable of anti-proliferative activity and induces apoptosis effectively against colon and lung cancer cells.

Learning is essential for understanding mental disorders, normal behavior, and forgetfulness. In this regard, the hippocampus plays an important role in the learning process. It has been reported that gamma-aminobutyric acid (GABA) receptors in the hippocampus are involved in learning and memory mechanisms and some diseases, such as epilepsy and Alzheimerchr('39')s. This study aimed to investigate the effect of coumarin on retention, tissue index, and GABA type A receptor gene expression in the hippocampus of male gonadectomy rats.

The population of this study consisted of 40 Wistar rats, which were randomized into 5 groups (n=8 each). These groups included healthy without treatment, gonadectomized without treatment, gonadectomized receiving solvent or Dimethyl sulfoxide, and gonadectomized receiving coumarin at a dose of 3.5 mg/kg. The treatment was administered intraperitoneally once daily in 2 weeks. A shuttle box was used to test the memory retention of the rats. At the end of the research process, the rats were exterminated in accordance with research ethics. After removing the brains of rats, in each group, in four brains histology test was implemented with Niels staining, and in four other brains, the hippocampus was removed quickly. The hippocampi were placed inside the micro type and frozen with liquid nitrogen. Finally, a gene expression test was taken from the hippocampus using a real-time polymerase chain reaction.

Based on the findings, in the memory retention test of initial latency to enter the dark room (step through latency), the gonadectomy group showed a reduction, compared to the healthy group.  Moreover, a significant decrease was observed in the number of healthy hippocampal pyramidal neurons; however, GABAA gene expression showed no significant difference. In the gonadectomy groups receiving treatments with different doses of coumarin, the amount of STL  (Step Through Latency) and number of healthy pyramidal neurons in the memory retention test showed a significant decrease, compared to the gonadectomy group receiving solvent; nonetheless, a significant increase was revealed in the GABAA-α2 gene expression.

It can be concluded that Gonadectomy caused memory impairment and coumarin affects memory impairment by increasing the GABAA-α2 gene expression and decreasing the number of healthy hippocampal neurons.

Lactobacillus reuteri has broad-spectrum effects on both gram-positive and negative bacteria as well as fungi and protozoa. Also, Coumarins have high ability to control and treat cancer. Apoptosis is a planned cell death that plays an essential role in the development and homostasis of living creatures. Bax and Bcl2 genes are among key target genes of internal pathway; thus the present study aimed to determine the effect of L. reuteri and Coumarin on the expression of these two genes on AGS cell line.

After cultivation of gastric cancer cells, Coumarin and L. reuteri were affected in these concentrations at different concentrations and the inhibitory effect on cell proliferation was evaluated using the MTT method. Afterwards, the RNA content of cells was extracted using an RNA extraction kit. Then the cDNA was synthesized for Bax and Bcl2 genes and finally Real time PCR was run.

The results of the MTT assay on gastric cancer cells showed the inhibitory effect of Coumarin and L. reuteri. Also, the results of Real Time PCR showed that the expression of Bax and Bcl2 expression in comparison with the control group was significantly increased.

Considering the effects of Coumarin and L. reuteri on inhibiting proliferation of AGS cells and increasing the Bax and Bcl2 gene, it can be concluded that Coumarin and L. reuteri can induce apoptosis in cancerous cells by affecting the expression of genes involved in apoptosis.

Medicinal plants of Genus Ferula are prennial herbs of Apiaceae family which are widely distributed all around the word. Many of Feula species are exclusive and endemic to Iran which has widespread uses in traditional medicine as food additive, as well as a carminative, antispasmodic and expectorants. Coumarins, flavonoids and sulfur-containing compounds with different biological effects have been reported from the plant.
The phytochemical investigation on total extract of the aerial parts of Ferula persica Willd var. Latisecta collected from the Central Alborz Protected Area was subjected with the aim of purification and determination of main metabolite constituents of the plant extract.
Dried and powdered plant material was extracted by maceration method. Then the extract was concentrated under reduced pressure to leave a residue which was defatted and chromatographed on a silica gel column by increasing slightly the polarity with solvent. After the serial fractionation the fractions were compared by TLC, and those giving similar coumarin spots were combined and further purified on PLC to give a pure natural compound.
After the purification step the remarkable constituents were obtained. Elucidation of results by spectral methods (IR, 1H-NMR, 13C-NMR and DEPT) demonstrate that a coumarin namely: Auraptene (7-genaryloxycoumarin) was isolated from the aerial parts of F. persica. var. latisecta.
F. persica is an endemic and endangered species of medicinal plants of Iran which contains different natural compounds such as coumarins. So the Protection of the plant for its economic and scientific uses is so important.

Ferula is a genus of about 130 species of flowering plants in the family Umbelliferae، of which 30 species are found in Iran. Many species of this family possess medicinal qualities and have long been used in traditional medicine. This research aims to isolate، separate and determine the structure of the compounds found in the chloroform extract of the aerial parts of Ferula hirtella. We collect F. hirtella form the site of its natural habitat in Ābāde، Fars Province. The chloroform extract of the aerial parts is derived and then mixture separation using Column chromatography is performed. Using Column chromatography purification methods، we were able to separate، for the first time، two coumarins، Farneciferol C and Umbelliprenin، and a steroid compound، β-stigmasterol from the chloroform extract of the F. hirtella which were identified using C NMR and H NMR spectral data. A majority of the compounds found in the chloroform extract of the aerial parts of F. hirtella are coumarins. Separation of β-stigmasterol from the chloroform extract of this genus was achieved for the first time.

Leishmaniasis has a wide range of clinical symptoms including cutaneous، mucocutaneous، and visceral leishmaniasis. Recently، advances have been observed in the field of using herbal medicines for the treatment of leishmaniasis. The study aimed to determine the in-vitro effect of two prenylated coumarins (oxypeucedanin and isoimperatorin) of Prangos ferulaceae (L.) Lindl with positive and negative controls on Leishmania major.

To have stationary phase of the growth curve، the parasites were cultured in NNN (Novy-MacNeal-Nicolle) and RPMI-1640 (Roswell Park Memorial Institute 1640) medias in the incubator. Then a certain amount of culture، containing approximately one million parasites، were exposed to oxypeucedanin and isoimperatorin and their effects were investigated after 3، 6، 24، 48، and 72 hours.

Non of the concentrations of oxypeucedanin and isoimperatorin had leishmanicidal effect compared to the positive control (P < 0. 05).

Oxypeucedanin and isoimperatorin do not have leishmanicidal effect on Leishmania major promastigotes.

Zireh Kermani, with the scientific name of Bunium persicum (Boiss.) B. fedtsch, is a plant belonging to Umbelliferae family. In some Iranian traditional medicine references, the fruits of Zireh are introduced as processed with vinegar and heat. Thus, the study examines qualitative and quantitative effects of this process on the plant compounds. Bunium persicum fruit was prepared from a standard source and then processed according to the method noted in Iranian traditional medicine references. Thin layer chromatography was used for determination of flavonoid and coumarin compounds of the plant. Additionally, polyphenolic compounds were measured by Folin-Ciocalteau method, before and after processing of the plant. Thin layer chromatography indicated that a certain amount of flavonoid and coumarin compounds entered vinegar. Presence of kaempferol and caffeic acid was observed in all samples of TLC analysis. Also, polyphenolic compounds increased in later stages of the process.Discussion and As by the process, a certain amount of flavonoid and coumarin compounds entered vinegar or changed by thermal effects and also polyphenolic compounds increase, the aims of this process can be decreasing the side-effects of the medicine and increase the particular effects.