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Formulation and optimization of effervescent tablet containing bismuth sub-citrate
Somayeh Taymouri, Abolfazl Mostafavi, Mohamad Javanmardi
July-December 2019, 8(2):236-244
Objective: The objective of this study was to design, evaluate and optimize effervescent tablets containing bismuth sub-citrate with sufficient hardness and friability in treatment of peptic ulcer. Materials and Methods: Effervescent tablets were prepared by direct compression method and were optimized using irregular factorial design. Amount of citric acid, sodium bicarbonate to citric acid molar ratio, polyvinyl pyrrolidone K 30 (PVP k30), polyethylene glycol 6000 (PEG 6000) were selected as independent variables, whereas disintegration time, amount of carbon dioxide (CO2), friability, pH, and hardness were selected as dependent variables. All the batches were assessed for various pre and post compression characteristics such as flowability, hardness, friability, effervescent time, pH, and content uniformity. For the enhancement of tablets’ palatability, the components of optimized formulation were mixed with same amounts of different flavoring agents. Results: The best results obtained from effervescent tablets prepared by 500 mg citric acid, 5% PEG 6000 and 3% PVP k30 while the molar ratio of the sodium bicarbonate to citric acid was 3. The disintegration time, amount of CO2, friability, pH, and hardness of optimized formulation were confirmed to be 95.33 ± 1.15sec, 398.73 ± 1.46 mg, 0.73%, 6.0 ± 0.06 and 72.3 ± 5.5 N, respectively. The most pleasant taste according to volunteers’ acceptability was the taste of cherry. Conclusion: These results suggest that developed effervescent tablets may be promising for delivery of bismuth sub-citrate in peptic ulcers therapy.
  3,913 440 2
Development of docetaxel-loaded folate-modified Poly(lactic-co-glycolic acid) particles
Yuri I Poltavets, Vasilisa V Zavarzina, Sergey L Kuznetsov, Anna A Krasheninnikova, Danil O Dronov, Nadezhda V Gukasova, Valentina G Shuvatova, Vadim Yu Balabanyan
July-December 2019, 8(2):253-261
Background: Poly(lactic-co-glycolic acid) (PLGA) particles with small vector molecules are used for targeted delivery of anticancer agents. To be effective, they must be small, noncytotoxic, sterile, and stable. Aim: The aim of this study was to prepare docetaxel-loaded folate-modified PLGA-based nanoparticles (FD-Dtx-NPs) and to assess their as parenteral folate-receptor targeted delivery systems during γ-sterilization and long-term storage. Materials and Methods: NPs were prepared by oil/water single emulsion-solvent evaporation method and simultaneous loading of polymer particles with docetaxel and folic acid derivative. NPs’ physicochemical characteristics and antitumor activity were assessed. Findings: FD-Dtx-NPs presented uniform characteristics over repeated measurements: ~250 nm size, <0.100 polydispersity index, and >2.5% docetaxel content in the finished lyophilizate. The observed slow docetaxel release from FD-Dtx-NPs was acceptable for proposed usage. γ-irradiated NPs were sterile under all tested protocols and maintained their physicochemical properties at a 10-kGy cumulative dose, 0.500 Gy/s dose rate, and 5.57-h exposure. No significant differences were observed in physicochemical characteristics of FD-Dtx-NPs over 12 months. Finally, FD-Dtx-NPs showed a high anticancer activity in vitro. Conclusion: The proposed method generates FD-Dtx-NPs with reproducible characteristics, high activity, and elevated stability during the long-term storage. Results of γ-sterilization and stability studies may be valuable for the development of polymer-based drugs.
  2,437 144 2
Pharmacognostic standardization and chromatographic fingerprint analysis on triterpenoidal constituents of the medicinally important plant Artocarpus heterophyllus by high-performance thin layer chromatography technique
Gunja Srivastava, Manjul Pratap Singh
January-June 2019, 8(1):1-12
Background: Artocarpus heterophyllus commonly known as Kathal in Hindi and Jackfruit in English has a wide horizon of medicinal possessions. The plant is found in India and in its tropical regions. Objective: Although the plant and its extracts are renowned for its ethnic medicinal values diversely in India, yet organized data somewhere lack in reverse pharmacognostical approach of this plant that shows that plant have not been completely explored for its therapeutic potency. Materials and Methods: In the present study, the folklore potential of this plant has been explored by generating down its pharmacognostical standards along with measurement of its active therapeutic constituent ursolic acid and lupeol via. High-performance thin layer chromatography (HPTLC), evidence from organized data search says that ursolic acid and lupeol is ubiquitous to A. heterophyllus. The plant was also subjected to spectroscopic-based estimation of tannins (gallic acid and tannic acid) and flavonoids (quercetin and rutin). Antimicrobial testing was also performed. Results: Microscopic features revealed the presence of anomocytic type of stomata, collateral open type vascular bundle in which fascicular cambium is present, calcium oxalate crystal and covering trichomes were key features in leaves. Methanolic extract of leaves of the plant was subjected to HPTLC. HPTLC studies revealed that both ursolic acid and lupeol are present in appreciable amount. Plant showed good antibacterial activity which may be due to the high amount of tannins as the tannins has the ability to disintegrate the bacterial cell wall. Conclusion: The data generated could be significantly used as a reference for the authentication and quality control of A. heterophyllus.
  2,046 512 -
Antioxidant activity and phytochemical screening of Ficus benghalensis aerial roots fractions
Zeinab Etratkhah, Seyed Esmaeil Sadat Ebrahimi, Nafiseh Khosravi Dehaghi, Yousef Seifalizadeh
January-June 2019, 8(1):24-27
Context: Ficus benghalensis (Moraceae) is an evergreen tree found in south and southeast of Iran as wild and cultivated plants. Different parts of this plant have different effects such as antitumor, antipyretic, analgesic and anti-inflammatory. Aims: The aim of this study was investigated the phytochemical screening and antioxidant activities of different fractions of plant roots. Materials and Methods: Phytochemical investigation was done by different methods in references. Antioxidant activity was evaluated by DPPH and FRAP assay. All chemical materials and solvents were prepared from Sigma-Aldrich, Scharlau and Merk. Statistical Analysis: All measurements were carried out in triplicate and the data were expressed as mean ± SD. Statistical analysis was performed using one-way analysis of variance (ANOVA) and tukey test. Results: Phytochemical screening showed steroids, flavonoids, tannins, phenolic compounds, and anthraquinone glycoside are F. benghalensis constituents. This plant had antioxidant activity, but it was lower than the Indian kinds. Conclusion: This study elucidated Ficus benghalensis could be useful plant with antioxidant activity. Further investigation needs for details.
  2,097 459 1
Green peas protein hydrolyzed by bromelain in simple procedure to improve kidney function in cisplatin-induced rats
Meilinah Hidayat, Sijani Prahastuti, Teresa Liliana Wargasetia, Kirana Nugraha, Andreanus Andaja Soemardji, Siti Farah Rahmawati, Nova Suliska, Khomaini Hasan
January-June 2019, 8(1):68-77
Context: Chronic kidney disease (CKD) can lead to terminal kidney failure. Previous study has shown that protein hydrolysate in yellow peas (Pisum sativum L.) can be used as a natural remedy for CKD. Aims: To obtain hydrolysate protein that is most effective in improving kidney function of cisplatin (CP)-induced Wistar rats, based on urea, creatinine, atrial natriuretic peptide (ANP), cyclooxygenase-1 (COX-1), and renin levels of CP-induced nephrotoxicity Wistar rats. Materials and Methods: Methods of Kjeldahl, Bradford, Kunitz, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis were used to determine the content of the eight types of protein hydrolysates. In in vivo experiment, the samples were administered to CP-induced nephrotoxicity Wistar rats, with urea, creatinine, ANP, COX-1, and renin as parameters. Results: Total neutrase activity was 40.65 U/mg, and bromelain was 35.77 U/mg. Total specific activities of both enzymes were almost identical. Protein hydrolyzed using bromelain had small fractions (<14.4 kDa). On the 30th day of treatment, urea and creatinine levels of all groups of treatment were significantly different from CP control (P < 0.01). The lowest level was shown by the group which was treated with bromelain-hydrolyzed green pea protein. Among ANP, COX-1, and renin measurements, only the result of COX-1 showed the promising result. Conclusions: Green peas protein hydrolysate hydrolyzed by bromelain are suggested as the most effective in improving kidney function based on urea, creatinine, and COX-1 levels of CP-induced nephrotoxicity Wistar rats.
  2,294 254 -
Investigation on the effects of Bactenecin on POPC membrane in atomistic details using molecular dynamics simulation
Seyran Saeidi, Elham Esmaeili, Mohabbat Ansari, Sajad Moradi, Mohsen Shahlaei
January-June 2019, 8(1):13-17
Background: Traditional antimicrobial agents are losing their efficiency as microbial resistance increases. Thus, developing antimicrobial peptides (AMPs) can assist as an alternative approach. For AMPs, the hypothesis mode of action is involved in pore formation within the lipid membrane, thereby leading to cell death. In this study, interaction between Bactenecin and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) was studied. Methods: For this purpose, two systems, Bactenecin in water and Bactenecin in POPC were treated by 50 ns of molecular dynamic simulation and data were compared with those of free POPC. Results: The results suggest that the interaction between Bactenecin and bilayer membrane cause some disorder and more instability along with little compactness of bilayer. The hydrogen bond between peptide and heads of lipid components may is main reason of membrane compactness. The results can provide some information on how to Bactenecin or other such peptides affect bio-membranes.
  2,123 328 -
Differential expression levels of agglutinin-like sequence, lipase, and secreted aspartyl protease genes in Candida tropicalis treated with fluconazole alone and in combination with clotrimazole
Alireza Khodavandi, Fahimeh Alizadeh, Maedeh Abdolahi, Mohammad Jahangiri
January-June 2019, 8(1):28-33
Background: The frequency of opportunistic fungal infections in immunocompromised patients, especially by Candida species, has sharply increased in the last few decades. As the number of antifungal drugs available for the treatment of candidiasis is limited, combination therapy has been employed as one of the most commonly used techniques to alleviate this problem. Aims: The main aim of this study was to explore the antifungal activity of fluconazole in combination with clotrimazole on expression levels of virulence genes, agglutinin-like sequences (ALS1 and ALS2), lipases (LIP1 and LIP4) and secreted aspartyl proteases (SAP2 and SAP4) in Candida tropicalis. Methods: Ten infected clinical isolates obtained from recurrent vulvovaginal candidiasis patients were used in this study. The broth microdilution assay was utilized to investigate antifungal susceptibilities to fluconazole alone and in combination with clotrimazole and the synergistic effects were interpreted with reference to the fractional inhibitory concentration (FIC) index model. The expression levels of ALS1, ALS2, LIP1, LIP4, SAP2 and SAP4 genes were quantified by real-time RT–PCR. Results: Antifungal susceptibility results showed that isolates were resistant to at least one type of azole antifungals. The combination of fluconazole with clotrimazole revealed synergistic effects against C. tropicalis isolates with FIC90 index ranging from 0.011 to 0.43. The results indicated that combination of fluconazole with clotrimazole could cause a down-regulation of gene expression of ALS1, SAP2, LIP4, SAP4, LIP1 and ALS2 genes, respectively. Conclusions: Fluconazole in combination with clotrimazole may diminish the virulence properties of C. tropicalis.
  2,019 264 -
New insights into the therapeutic effects of phenolic acids from sorghum seeds
Reda Ben Mrid, Youssef Bouargalne, Redouane El Omari, Mohamed Nhiri
January-June 2019, 8(1):91-101
This paper reviewed the beneficial effects of the major phenolic acid compounds of Sorghum bicolor seeds. Different studies were reviewed to determine the major phenolic acid components of sorghum seeds. Several kinds of literature were then analyzed to discuss the different beneficial effects of these molecules. S. bicolor is an important source for food and feed. It is among the top five crops regarding its production and consumption throughout the world. Till date, many studies highlighted different aspects of the biochemical and physiological properties of sorghum grain. However, studies concerning the pharmacological properties of sorghum grain are scarce. The predominant phenolic acids of sorghum seeds are ferulic, p-coumaric, and protocatechuic acids. The bioactive effects of these phenolic acids are mainly related to their antioxidant, antitumor, antidiabetic, antimicrobial, cardiovascular, and gastrointestinal activities. The data collected from recent studies indicate that these molecules have a promising future as natural agents for the treatment of various diseases, and this is particularly due to their strong antioxidant properties. This review provides evidence for the importance of sorghum seeds and their phenolic compounds in the prevention and treatment of several diseases. This work showed that sorghum grains are a good source of beneficial and therapeutic molecules. It also recommended the addition of sorghum grains to human diet as other cereals because of its high nutritional value.
  1,912 304 -
Preparation and pharmaceutical evaluation of ferrous sulfate and ascorbic acid floating matrix tablet for prevention of anemia
Rahim Najafi Bahri, Lotfollah Saghaei, Taher Babaeimehr
July-December 2012, 1(2):72-80
For prolonging the time that drug remains in stomach, new methods used as floating drug delivery systems, that available in various forms such as floating tablets. These systems enhance drug absorption and decrease plasma concentration fluctuations. Iron deficiency and its inadequate absorption in diet are of community health problems. Common forms of iron available in the market have little bioavailability and due to greater excretion of drugs from the gastrointestinal tract has many complications such as constipation. Using floating systems to enhance drug absorption can reduce the dose required and drug side effects. In this study, preparation of floating tablets of ferrous sulfate plus ascorbic acid is considered since it has proven that vitamin C enhances iron absorption. Tablets were prepared with swollen polymers like HPMC K4M and carbopol934 by direct compression method. Sodium bicarbonate and citric acid was used to create the CO2 then drug properties such as buoyancy, release percentage and physical properties were tested on that. Tablet formulation No. 10, started to float in 27 seconds and floating state lasts 18 hours in environments like stomach. According to the great drug release and long floating state (12 h), tablet formulation 10 is recommended as a drug supplement to prevent anemia.
[ABSTRACT]   Full text not available  [PDF]
  1,827 367 -
Quantitative structure–activity relationship analysis of thiophene derivatives to explore the structural requirements for c-Jun NH2-terminal kinase 1 inhibitory activity
Ashima Nagpal, Monika Chauhan
July-December 2019, 8(2):115-123
Background: With an aim to design a validated two-dimensional quantitative structure–activity relationship (2D QSAR) model, a probe was executed on a series of reported c-Jun NH2-terminal kinase-1 (JNK1) inhibitors, exhibiting selectivity toward JNKs (and not other members of MAPK family). Objective: The present work focused on obtaining valuable insights from the structural architecture of the selected compounds and their effects on JNK1 inhibitory activity. The present work deciphers the importance of descriptive variables, namely Verloop L (Subst. 1), Bond Dipole Moment (Subst. 2), LogP (Subst. 1), Balaban Topological index (Subst. 1), and  VAMP Total Dipole (whole molecule), in molecules possessing JNK1 inhibitory profile. Results: These explanatory variables, obtained after iteratively reducing the data, did not only provide us with the substantial evidence pertaining to the dependence of bioactivity on the structural features of molecules, but also suggested the measures to optimize the selected compounds so as to obtain potent JNK1 inhibitors with good selectivity profile. Based on these distinct descriptors, exhibiting no apparent intercorrelation and manifesting good correlation with biological activity, a 2D QSAR model was generated. Conclusion: Robustness of the developed model was evaluated by performing multiple linear regression, partial least square, and artificial neural network studies. The reliability and predictive ability of the developed model was ascertained through the values of standard statistical parameters, such as s = 0.38, F = 97.22, r = 0.95, r2 = 0.90, and r2cv = 0.88, for the training set compounds. The generated model was validated through the test set compounds, as well as by leave one out method.
  1,782 389 -
The effect of ibuprofen on expression of Cox-1/2-related miRNAs in MKN- 45 -derived cancer stem-like cells
Hassan Akrami, Behnam Karimi, Zohreh Salehi, Sajjad Sisakhtnezhad
January-June 2019, 8(1):18-23
Context: Ibuprofen is an anti-inflammatory drug that non-selectively blocks cyclooxygenases-1/2 (COX-1/2) enzymes and thus reduces the risk tumorigenesis. This study was designed to detect microRNAs (miRNAs) that target Cox-1/2 mRNA and to investigate the effect of ibuprofen on the expression of the miRNAs in MKN-45-derived gastric cancer stem-like cells (CSLCs). We were also aimed to find signaling pathways modulated by the miRNAs. Subjects and Methods: The miRWalk database was used to recognize miRNAs that targeted Cox-1/2 genes. CSLCs were derived from MKN-45 cell line and were then treated with ibuprofen. Consequently, the effect of ibuprofen was evaluated on the expression of the miRNAs by quantitative real-time polymerase chain reaction (qRT-PCR). Finally, DIANA tools were used to identify signaling pathways that modulated by the miRNAs. Results: Our bioinformatic investigation showed that hsa-mir-16-5p, hsa-mir-483-5p, and hsa-mir-4669 targeted both Cox-1 and Cox-2 mRNAs. The qRT-PCR results indicated that hsa-mir-16-5p and hsa-mir-4669 were overexpressed 2.34 and 9.47 folds, respectively, while hsa-mir-483-5p under-expressed (2.08 folds) in ibuprofen-treated CSLCs relative to untreated cells. Moreover, it found that these miRNAs are involved in PI3K-Akt, P53, transforming growth factor-beta, phosphatidylinositol and insulin signaling pathways, cell cycle, extracellular matrix receptor interaction, gap junction, small cell lung cancer, prostate cancer, and chronic myeloid leukemia. Conclusions: We suggest that ibuprofen may reduce the risk of gastric cancer by affecting the expression of miRNAs that target Cox-1/2. however, further research is necessary to unravel its exact effects.
  1,614 311 -
In vitro cytobiological effects of phytochemicals from Artemisia turanica
Mahboubeh Taherkhani
January-June 2019, 8(1):106-113
Background: Phytochemicals from the plants have been used as traditional medicine and can cause many biological effects such as antimicrobial, anticancer, mutagenic and etc. Aims: The subject of this research was to determine the chemical constituents and evaluate the antimicrobial, anticancer, cytotoxicity, mutagenic and anti mutagenic activities of the volatile oil of Artemisia turanica Krasch. Material and Methods: Antimicrobial properties were measured by agar disc diffusion method. Cytotoxicity was determined through 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide method on human lymphocytes and cancer HeLa cells. Toxicity, mutagenesis, and anti-mutagenesis effects of the essential oil were measured by the Ames Salmonella mutagenicity method, in the existence or absence of S9 as a metabolic activation. Results: Oxygenated monoterpenes, especially 1,8-cineole (35.2 %), α-thujone (24.2 %) and cis-chrysanthenol (16.8 %) were the main components in this volatile oil. Bactericidal kinetics of the volatile oil of A. turanica indicated that Esherichia coli is the most vulnerable one (minimal inhibitory concentration = 2.5 mg/ml, D value = 6.43 min). Cytotoxicity of the A. turanica oil in the human tumor cell line (17.67 μg/ml) was more than that observed in normal human lymphocytes (3291.49 μg/ml). Volatile oil of A. turanica showed suitable antimutagenic potency on 2-nitrofluorene, in the strain of Salmonella typhimurium TA98, without the existence of metabolic activation S9. Conclusion: The results achieved by human cells and with S. typhimurium prove that the volatile oil of A. turanica may be exploited as a natural anticancer and antimutagenic agent with low adverse side effects.
  1,678 176 -
Therapeutic effect of Ferulago angulata extract on reproductive parameters and serum testosterone levels in diabetic male rats
Glavizh Rostami Nassab, Somayeh Bohlouli, Ali Ghanbari
January-June 2018, 7(1):1-8
Diabetes is an important metabolic disease inducing different effects on body organs, especially reproductive system. Increased oxidative stress and antioxidant capacity changed in diabetes induce infertility and decrease the sperm parameters. This study was to evaluate the therapeutic effects of hydro alcoholic extract of Ferulago angulata on reproductive parameters in diabetic male rats. In this experimental study, we used 30 male Wistar rats (230- 250g) with an average age of 10 weeks. A total of 24 rats were made diabetes type I by 40 mg/kg streptozotosin. Animals were divided into 5 groups of control, diabetic, and diabetic+ Ferulago angulata extract (100, 200 and 400mg/kg). Sperm parameters, serum testosterone level, seminiferous tubules diameter, and germ line epithelium maturity were assayed at the end of study. Data were analyzed by one-way ANOVA test and P<0.05 was considered statistically significant. Our results showed serum testosterone level and sperm parameters, including count, viability, progressive motility, and normal morphology as well as seminiferous tubules diameter and germ line epithelium maturity of diabetic male rats increased at 200 and 400 mg/kg doses of Ferulago angulata extract (P<0.05). The hydroalcoholic extract of Ferulago angulata, an herbal plant with abundant antioxidants, improved the quality of sperm and reproductive parameters in diabetic male rats.
[ABSTRACT]   Full text not available  [PDF]
  1,122 717 -
Experimental design approach in erythropoietin-alginate microsphere preparation with different concentrations of drug and polymer
Dewi Melani Hariyadi, Tristiana Erawati, Vita Fitria Ramadhani
January-June 2019, 8(1):78-84
Background: Microspheres as drug delivery system has been selected to increase stability of Erythropoietin (EPO) to achieve efficacy. Aim: Aim of this research was to determine effect of polymer and EPO concentrations on the characteristics. Materials and Method: Microspheres involved sodium alginate as polymer and CaCl2 as a crosslinker. The concentrations of sodium alginate used were 2% and 3%, and EPO were 5000 IU and 10000 IU. Formula of microspheres which consist of 2% and 3% of alginate and 5000 IU EPO were called F1 and F2 respectively, whereas microspheres using 2 and 3% alginate and 10000 IU EPO was named F3 and F4 respectively. Characterization including morphology, particle size, swelling index, and yield of microspheres prepared by ionotropic gelation aerosolization technique. Design of Experiment (DoE) was used to analyze the formula. Results: Results showed that particle sizes of EPO-alginate microspheres were 3.36 ± 0.126μm, 3.42 ± 0.098μm, 3.88 ± 0.131μm and 3.95 ± 0.151μm for F1, F2, F3 and F4 respectively. The swelling index measurement based on mass and particle size of microspheres of all formulas showed an index of less than 10. Respectively, yield was 77.84 ± 0.290%, 86.65 ± 0.191%, 91.89 ± 0.210%, and 94.65 ± 0.252% for F1 to F4. Using the ANOVA factorial design, it was found that increasing sodium alginate concentration significantly increased yield, while increasing EPO concentration significantly increased particle size and yield of microspheres. Both sodium alginate and EPO concentrations did not affect swelling index of microspheres. Range concentrations of sodium alginate and EPO that produced optimal characteristics of microspheres can be observed in the feasible area of design space overlaid contour plot generated from DoE study. Conclusion: EPO-alginate microspheres demonstrated the prospective as carrier and DoE is potential for further optimized formulations.
  1,589 235 -
Effect of sodium benzoate on liver and kidney lipid peroxidation and antioxidant enzymes in mice
Forouzan Khodaei, Hossein Kholghipour, Masood Hosseinzadeh, Marzieh Rashedinia
July-December 2019, 8(2):217-223
Introduction: Sodium benzoate (SB), as a chemical preservative, is used in many kinds of foodstuff. Some studies reported toxicity effects of SB in food products and suggested to limit its usage. The aim of this study was to evaluate the effects of oral administration of SB on antioxidant enzymes and lipid peroxidation in the liver and kidney of mice. Materials and Methods: A total of 24 animals were divided into four groups: Control group and three treated groups that received 150, 300, and 600 mg/kg/day of SB, respectively, in drinking water for 4 weeks. The malondialdehyde level, glutathione (GSH) content, superoxide dismutase (SOD), and catalase (CAT) activities of the liver and kidney were measured and the results of the treated groups were compared with those of the control group (one-way analysis of variance). Results: Results showed that SB caused histological alterations in the liver and kidney tissues. Moreover, SB significantly increased lipid peroxidation and GSH content in the kidney tissues (P < 0.05). Also, CAT activity significantly declined in the kidney (P < 0.05), without changing the SOD activity, but SB did not have any effect on the biochemical parameter of the liver tissue. Conclusion: The results of this study showed that SB caused kidney injury more than liver injury, but as a food preservative, which is consumed for a long period of life, it may cause liver damage additionally. For that reason, the excessive SB intake in the food is disturbing.
  1,601 196 2
Analysis of phenolics in Calligonum polygonoides in vitro cultured roots
Asmaa I Owis, Nada S Abdelwahab, Adel A Abul-Soad
July-December 2019, 8(2):124-127
Background: Calligonum polygonoides L. subsp. Comosum (L’Hér.) Sosk. is an endangered plant species belonging to family Polygonaceae. Although the plant is rich in phytoconstituents and has multipurpose medicinal applications, but in vitro root culture studies and phytochemical investigations of these cultures are rare. Objectives: To establish in vitro root, callus and cell suspension cultures from in vitro germinated fruits of C. polygonoides to investigate the production of phenolics through root, callus and cell suspension cultures and attempt to enhance cell capacity to accumulate phenolics. Materials and Methods: Modified Murashige and Skoog medium supplemented with 1 mg l-1 indole-3-butyric acid was used to establish the root culture. Elicitation of cell suspension culture was performed using salicylic acid and yeast extract. The phenolic compounds in root, callus and cell suspension cultures were evaluated using reversed phase high performance liquid chromatography technique. Results: The unorganized cell suspension culture contained fewer amounts of phenolic compounds than the differentiated roots tissue. Elicitation produced quantitative reprogramming of phenolic content. Conclusion: The present study provides a chance to improve secondary metabolite yield from this valuable natural plant.
  1,462 331 -
Chemical composition, antibacterial and antioxidant activities of Tagetes patula L. essential oil raised in Erbil, Iraq
Ausama A Safar, Anwar O Ghafoor, Dara Dastan
January-June 2020, 9(1):59-67
Background: Over the years, management of human pathogenic microorganisms has primarily relied on the use of synthetic antibiotics. In the recent past, Tagetes patula essential oils (EOs) and their phytochemistry and bioactivities have received great attention in research. Purpose and Methods: In this study, the component, antimicrobial activity, and antioxidant capacity (ferric-reducing antioxidant power assay) of EOs from five plant parts (shoot at vegetative growth stage [TPSV], shoot at flowering growth stage [TPSF], flower [TPF], fruit [TPS], and root [TPR]) of T. patula were investigated. The antibacterial activity against five gram-negative bacterial isolates (including Serratia fonticola, Klebsiella pneumoniae, Acinetobacter baumannii, Proteus mirabilis, and Escherichia coli) and five gram-positive bacterial isolates (including Staphylococcus aureus, S. epidermidis, S. saprophyticus, Streptococcus agalactiae, and Streptococcus oralis) was studied using broth microdilution method. FRAP assay was also used to evaluate their antioxidant activity. Results: One hundred and twenty-five compounds of the total EOs were identified, constituting a mixture of oxygenated monoterpenes (33%), monoterpene hydrocarbons (25%), oxygenated sesquiterpenes (19%), sesquiterpene hydrocarbons (12%), and furanocoumarins (8%). In this paper, for the first time, more than 60 new compounds were isolated from T. patula such as bergapten, sylvestrene, (E)-β-farnesene, (E)-epoxy-ocimene, (Z)-jasmone, γ-gurjunene, and γ-himachalene. The EOs of T. patula showed potent antibacterial activity against the studied bacteria with the highest growth inhibition observed in E. coli after 24 h of incubation (MIC value 0.08 and MBC value 0.32 µL/mL). The TPS-EO had the highest mean value for ferric-reducing ability at the three test times, whereas TPR-EO had no activity. Conclusion: It was concluded that the potential biocidal activity of T. patula EOs could be substantially associated with their oxygenated constituents or the synergistic activity of their major and minor chemical components.
  1,681 106 -
Evaluation the effects of Cissus modeccoides hot aqueous extract on alloxan-induced diabetic rats
Waranee Pradit, Taddaow Khumpook, Kanokporn Saenphet, Supap Saenphet, Siriwadee Chomdej
January-June 2019, 8(1):85-90
Introduction: In this study, the hypoglycemic effects and the safety of Cissus modeccoides (CM) were assessed on alloxan-induced diabetic rats. Methods: Various concentrations of CM hot aqueous extract were orally administered to alloxan-induced diabetic rats for 30 days. Blood glucose level, hematological and biochemical parameters, and gene expression level were evaluated. Results: After CM treatment, diabetic rats presented nonreduced blood glucose level and unimproved body weight. Increased blood urea nitrogen was observed in CM-treated groups as well. Although hematological parameters and cholesterol level revealed nonsignificant effects from CM, decreased expression levels of the insulin receptor in the pancreas and insulin receptor substrate 2 and glucose transporter 2 in the liver were demonstrated in CM-treated groups. Nephrin in the kidney of CM groups was highly expressed. Conclusion: The results of this study revealed adverse effects and toxicity of CM extracts in diabetic rats.
  1,537 195 -
Acetyl glycyrrhetinic acid methyl ester as a promising glycyrrhizin derivative against the breast cancer cells (MCF-7)
Mohamed G Ibrahim, Fardous F El-Senduny, Magdy M Youssef, Diaaeldin M Elimam, Fatma M Abdel Bar, Farid A Badria
July-December 2019, 8(2):161-171
Background: Breast cancer remains the most potent threat to women’s life worldwide. So far, no ideal drug for treatment of breast cancer, all available drugs exhibit severe side effects, poor therapeutic index, and high cost. Objective: Therefore, this study aimed to investigate the potential use of the natural pentacyclic triterpenoids such as Boswellic, Betulinic (BA), Urosolic, Oleanolic acids, Glycyrrhizin and their derivatives for treatment of breast cancer. Materials and methods: The cell viability was firstly determined after treatment with 50 µM of each compound. The effect of the treatment on cell cycle, apoptosis, cell migration and colony formation was evaluated. The ability of the new glycyrrhizin derivative to activate p53 was investigated by flow cytometry. Results: The cytotoxicity assay revealed that glycyrrhizin derivative AM-GA (3-acetyl-18β-glycyrrhetinic-30-methyl ester) and BA were the most cytotoxic against breast cancer cell line MCF-7 with IC50 values 4.5±0.1 and 4±0.1 µM, respectively. Both AM-GA and BA were selective towards breast cancer cells rather than the normal lung fibroblast cell line WI-38. Both AM-GA and BA were able to inhibit the cancer cell migration in the wound healing assay and inhibited colony formation. Studying the mechanism of action revealed that AM-GA inhibited the growth of the breast cancer cells via cell cycle arrest at sub-G1 phase, induction of apoptosis and activation of the tumor suppressor protein p53. Conclusion: This work highlights the unique role of AM-GA against breast cancer via different mechanisms and will be the gate for new potent analogues and fights different cancer types.
  1,515 155 -
Appraising the neuroprotective competence of nitrogen-enriched Arthrospira platensis in comparison to commercial resource in depressed mice models
Arockiya Anita Margret, Muppliyan Kalaiyarasan, Arockiya Avila Jerley, Theboral Jeevaraj
July-December 2019, 8(2):139-148
Back ground: Arthrospira platensis encompasses vital nutrients and is commercialized globally. It comprises of imperative resource that has the potential to combat neurological deformities caused due to stress and anxiety. Objective: This work evaluates the neuroprotective effect of spirulina cultivated on nitrogen enriched medium and compares it with the commercial samples. Materials and Methods: The study is authenticated with an antioxidant assay and the vital compounds are relatively profiled by GC-MS study. Furthermore, a molecular docking analysis is implemented to investigate the therapeutic potentials of the phytocompounds against Monoamine Oxidase –A and establish them as inhibitors. The ethanolic extract of spirullina as are fed on depressed mice models to assay its neuroprotective effect and rehabilitation of brain cells by a histopathological study. Results: The antioxidant content of the augmented sample was consistent on par with the commercial sample. The in silico assay was performed with 10 extricated compounds of both the samples where, Butanoic acid, 3-hydroxy- furnished a minimum binding affinity energy value of -56.24 kcal/mol and dodecanamide was efficient to bind with the active site of the amino acid residue TYR 69 with a minimum energy of -87.8 kcal/mol. The histopathological examination upholds the refurbished parameter of vital phytocompounds with placid cellular edema and perivascular infiltration. Conclusion: There is a wide range of need to develop research against stress and anxiety and the study fortifies the restorative efficacy of the phytocompounds as a neuroprotective drug.
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Formulation and evaluation of Neem (Azadirachta indica A. Juss) seed oil suppositories
Olusola I Aremu, Kokonne E Ekere, Yetunde C Isimi, Victoria C Nwaogu, Olawale G Agbaje, Olubunmi J Olayemi, Musiliu O Adedokun, Martins O Emeje
July-December 2019, 8(2):245-252
Background: Neem seed is very vital because of its rich lipid content and bitter constituents. Aims: This study was designed to provide a scientific rationale for the preparation and use of Neem seed oil as suppositories using dika fat (DF), and macrogol (MG), as bases. Materials and Methods: The suppositories which were prepared by fusion method using a pre-calibrated mould, were characterized using parameters like appearance, crushing strength, weight variation, melting point, pH, liquefaction time and in-vitro release according to standard procedures. Results: Results show that, the suppository strengths were in the order; bland, MG (25.00 ± 1.50N) > DF (12.90 ± 0.72 N), while those containing medicaments were NSM1 (20.00 ± 1.92) > NSD1 (12.90 ± 0.94) > NSM2 (12.70 ± 1.24 N) > NSD2 (10.00 ± 1.35 N). The pH of medicated formulations were NSM1 (6.50 ± 0.01), NSM2 (6.54 ± 0.03) > NSD1 (5.73 ± 0.04) and NSD2 (5.07 ± 0.03). Melting point values show that, macrogol base had mean values of 36.80 °C ± 0.62 and 36.40 °C ± 0.46 for NSM1 and NSM2 respectively, whereas, those with DF gave an average melting point values of 32.10 °C ± 0.87 and 30.90 °C ± 0.79 for NSD1 and NSD2 respectively. Conclusion: Results obtained showed that suppositories prepared with Macrogol (MG) base exhibited better physicochemical properties than Dika fat (DF) base suppositories, therefore water soluble bases may be bases of choice in the delivery of neem seed oil.
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Apoptosis cell death effect of linoleic acid from nigella sativa on human ovary cancer cells through mitochondrial intrinsic pathway
Yalda Shokoohinia, Gholamreza Bahrami, Fatemeh Taherabadi, Fataneh Jaffari, Leila Hosseinzadeh
January-June 2018, 7(1):20-26
In this study, we evaluated the cytotoxic potential of fractions (F1-F5) isolated from hexane extract of the seeds of N. sativa on human ovarian carcinoma cell line, A2780. F2 showed an outstanding potent cytotoxic effect against A2780 cells. Next, this fraction was purified to obtain six sub-fractions (SF1-SF6) and their cytotoxic effects were then evaluated. The obtained results showed that SF2 had strong cytotoxic effect against A2780 cell line. The effective sub-fraction (SF2) was determined to be linoleic acid (LA) according to spectroscopic analyses. In the next set of experiments, the apoptotic potentials of LA were investigated. Induction of apoptosis by LA was accompanied by an increase in activation of caspase-3, -9 and reduction in mitochondrial membrane potential (MMP) in A2780 cells. It can be concluded that LA, inhibited the growth of human ovarian carcinoma cells, A2780 and induced mitochondrial-related apoptosis.
[ABSTRACT]   Full text not available  [PDF]
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Evaluation of potential drug-drug interactions in patients with hematologic malignancies at a referral hematology–oncology hospital: A single-center experience
Sara Ataei, Kaveh Ardalani, Maryam Mehrpooya, Mojdeh Mohammadi
July-December 2019, 8(2):284-288
Background: Drug-drug interaction (DDI) is a complication that results from the combined use of two or more drugs. DDIs can create problems and increase drug toxicity. In some DDIs, a drug can reduce the effectiveness of other drugs. The treatment regimen of hematologic malignancies includes various medicines. Patients may have another disease and receive other medicines in their treatment regimen, resulting in an elevation of DDI rate. This study was aimed to study the rate, pattern, and probable risk factors for moderate and major interactions. Subjects and Methods: In this cross-sectional study, data including type of administrated drugs, type of malignancies, and patients’ demographic data were obtained from medical records of patients referred to Tohid Hospital, Sanandaj, Iran, between 2011 and 2015. Major or moderate interactions were considered eligible for further analysis and minor interactions were excluded. DDIs were identified by Lexicomp software and Drug Interaction Facts book. Data analysis was carried out by descriptive statistics. Results: A total of 441 DDIs (moderate to major) were identified in 76 patients. DDIs in men were higher compared to women. In addition, most of the interactions in terms of intensity were moderate (62% of total interactions) and in terms of mechanism were pharmacodynamic (60% of total interactions). Interaction between acetaminophen and granisetron had the highest frequency. Among cancer drugs, cyclophosphamide (7% of total interactions) and among non-cancer drugs, granisetron (10% of total interactions) had the highest frequencies. Conclusion: Moderate or major DDIs occurred frequently in patients with blood cancer or related diseases. Most of the found DDIs were categorized as moderate with regard to severity. DDIs identification by the treatment team and replacement of treatment regimen will impose fewer complications on patients and increase patients’ survival.
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Antioxidant activity of the Ferula gummosa Boiss.'s aerial parts: Measurements based on different assay methods
Abdoreza Nazari, Elham Golezar, Hamid Mahdiuni
January-June 2019, 8(1):61-67
Introduction: Measuring of natural antioxidants power is important in the food industry. Ferula gummosa Boiss. plant, locally called Barijeh, is a member of genus Ferula belonging to the Apiaceae family. To introduce endemic natural antioxidants, antioxidant capacity of alcoholic and hydroalcoholic extracts of aerial parts of F. gummosa Boiss. was investigated. Objective: The primary objective of this study was to compare the antioxidant levels and activities between flower and leaf extracts of Ferula gummosa Boiss. plant by different assay methods. Method: The antioxidant activity of flower and leaf extracts of F. gummosa Boiss. was assessed usingferric-reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and oxygen radical absorbance capacity (ORAC) assay. In addition, phenolic content of the extracts was measured byFolin-Ciocalteu (FC) method. Results: Ferric reducing antioxidant power assay showed that leaf extract has more antioxidant activity compared to flower extract. DPPH assay had similar results. A slow kinetic behavior was found for methanol extracts of both tissues (EC50 of 0.21 mg/mL and 0.25 mg/mL for leaf and flower methanol extracts, respectively) which was estimated by kinetic mode of DPPH assay. The ORAC assay showed higher values for methanolic extracts compared to ethanolic extracts. Except for ORAC assay, a significant positive correlation was found between antioxidant data of ferric-reducing antioxidant power, DPPH and Folin-Ciocalteu assays. Conclusion: These findings suggest that high antiradical potential and reducing power of the alcoholic and hydroalcoholic extracts of the aerial parts of F. gummosa Boiss. correspond to a high phenolic content in these plant parts. The high antioxidant activity of the F. gummosa Boiss. could propound the hydroalcoholic extracts of this plant as a therapeutic agent to prevent and treat diseases due to free radical imbalance in the body.
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Comparative phytochemical screening, in vivo antioxidant and nephroprotective effects of extracts of cassava leaves on paracetamol-intoxicated rats
Israel O Okoro, Helen E Kadiri, Eferhire Aganbi
July-December 2019, 8(2):188-194
The phytochemical screening, antioxidant, and nephroprotective effects of methanol and acetone extracts of cassava (Manihot esculenta Crantz) leaves were comparatively investigated using standard procedures. Fifty-four male Wistar rats (albino) were divided into nine groups of six rats each. Group 1 = negative control (normal untreated rats + normal saline); group 2 = positive control (rats + 2g/kg bw acetaminophen + normal saline), groups 3, 4, and 5 = 200 mg/kg bw, 100 mg/kg bw, and 50 mg/kg bw of methanol extract, respectively, + 2g/kg bw acetaminophen; groups 6, 7, and 8 = 200 mg/kg, 100 mg/kg bw, and 50 mg/kg bw of acetone extract, respectively, + 2g/kg bw acetaminophen; and group 9 = 100 mg/kg silymarin + 2g/kg bw acetaminophen. The phytochemical screening of the methanol and acetone leaves extracts showed the presence of flavonoids, alkaloids, saponins, anthocyanins, tannins, and triterpene, whereas, cardiac glycoside, steroids, and anthraquinone were absent in both extracts. Acetaminophen administration significantly elevated the levels of serum urea, creatinine, sodium, and potassium with a corresponding decrease in the levels of total protein, albumin, and calcium in the group 2 rats compared with that in the group 1 rats. Similarly, the levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione, and glutathione S-transferase were significantly less in the acetaminophen-intoxicated group than that in the negative control group. However, pretreatment with either extracts, dose dependently prevented the acetaminophen-induced derangement of the aforementioned parameters. The extracts showed antioxidant activity similar to the reference drug (silymarin). Comparatively, the methanol extract gave higher in vivo antioxidant and nephroprotective effects than the acetone extract. The results suggest the extracts of cassava leaves have high nephroprotective potential and may be based on their phytoconstituents and antioxidant activity.
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