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   Table of Contents - Current issue
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January-June 2020
Volume 9 | Issue 1
Page Nos. 1-175

Online since Friday, June 26, 2020

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ORIGINAL ARTICLES  

Quantitative bioanalytical and analytical methods for estimation of ivabradine hydrochloride in pure and pharmaceutical dosage form p. 1
Anjali Polker, Yenumula Padmavathi, Ravi Kumar, Nayaka Raghavendra Babu
DOI:10.4103/jrptps.JRPTPS_110_19  
Introduction: New analytical and bioanalytical methods were developed for the estimation of Ivabradine hydrochloride in bulk and pharmaceutical dosage form by UV spectrophotometry and high-performance liquid chromatography (HPLC) technique. Objective: The primary objective of the study is to develop a new RP-HPLC method for estimation of Ivabradine Hydrochloride in pure and formulation and to develop a bioanalytical method for analysis of Ivabradine Hydrochloride in biological samples. The methods were validated as per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and USFDA guidelines respectively. Methods: In Reversed-phase (RP)-HPLC method developed telmisartan is the internal standard used. After liquid–liquid extraction, the analyte and the internal standard were chromatographed on Waters 125A (10 µ, 300 × 3.9 mm) C18 column using 20-µL injection volume with a run time of 15 min. An isocratic mobile phase consisting of acetonitrile and ammonium acetate buffer pH 7.8 (60:40% vol/vol) is used to separate drug and internal standard. In Spectrophotometric bioanalytical method developed for the estimation of ivabradine hydrochloride in pure and pharmaceutical dosage form. The solvent system used is absolute methanol and detected at the wavelength of 287 nm. The solvent system used is absolute methanol and detected at the wavelength of 287 nm. Results: The Analytical method is validated according to ICH guidelines over the range of 2–16 μg/ mL, showing accuracy, precision, selectivity, and robustness. For Bioanalytical method the linearity is established in the range of 500–3500 ng/mL with the regression coefficient of r2 = 0.9994. The validated spectrophotometric method is used successfully to study ivabradine hydrochloride in rat plasma and also quantitative determination in marketed tablets. Conclusion: The proposed methods were successfully applied for the quantitation of ivabradine hydrochloride in pharmaceutical dosage form with good recovery and reproducibility.
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In silico analysis of miRNA role in resistance of hepatocellular carcinoma Bel-7402 cells to TRAIL p. 11
Zohreh Salehi, Homeyra Seydi, Paria Hadadi, Omid Tavallaei
DOI:10.4103/jrptps.JRPTPS_18_19  
Context: To this date, the exact basics of microRNAs (miRNAs) mechanisms in inducing a resistance to tumor necrosis factor –related apoptosis-inducing ligand (TRAIL) signaling pathways remain unclear. Aims: The aim of this study was to analyze miRNA signaling pathways in TRAIL-resistant Bel-7402 cell line. Materials and Methods: The Gene Expression Omnibus (GEO) database was studied for miRNA expression profiling studies in TRAIL-resistant versus TRAIL-sensitive Bel-7402 cells. By searching through databases of DIANAmT, miRanda, miRDB, miRWalk, and PICTAR using the online tools of miRWalk and TargetScan, target genes of miRNAs were predicted to express differentially by up to 50% in TRAIL-resistant versus TRAIL-sensitive Bel-7402 cells. Afterwards, signaling pathways and biological functions of miRNA target genes in TRAIL-resistant versus TRAIL-sensitive Bel-7402 cells were analyzed by the DAVID database. Results: A total of 352 miRNAs (186 up- and 166 downregulated miRNAs) were obtained from GSE74130 GEO DataSets accession item. The upregulated miRNAs including hsa-mir-145, hsa-mir-188, hsa-mir-221, hsa-mir-4802-5p, hsa-mir-198, hsa-mir-1184, and hsa-mir-345-3p were significantly intensified in apoptotic signaling pathway and process. The downregulated miRNAs including hsa-mir-138, hsa-mir-375, hsa-mir-449, hsa-mir-637, hsa-mir-208-3p, hsa-mir-4783-5p, hsa-mir-548b-3p, hsa-mir-127-3p, hsa-mir-92b-5p, hsa-mir-375, hsa-mir-503-5p, hsa-mir-499a-3p, and hsa-mir-154-3p were significantly raised in expression in cancer stem cell pathways. Conclusions: Analysis of miRNA expression profile revealed that some of the upregulated miRNAs negatively contributed to the regulation of apoptosis signaling pathways and cell cycle arrest as well as promoting TRAIL-induced apoptosis resistance in TRAIL-resistant Bel-7402 cells. Also, down-regulated miRNAs were probably involved in cancer stem cell processing.
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In vitro cytotoxic activity of Verbascum alceoides against cervix carcinoma cells p. 19
Masoud Sadeghi Dinani, Samin Malakooti, Vajihe Akbari
DOI:10.4103/jrptps.JRPTPS_65_19  
Background: Verbascum species showed various pharmacological activities including anti-inflammatory, antitussive, antiulcerogenic, immunomodulatory, antimicrobial, antimalarial, antioxidant, and anticancer activities. Objectives: The aim of this work was to evaluate cytotoxicity of different fractions of Verbascum alceoides, which belongs to this genus. Materials and Methods: Aerial parts of this plant were collected from Doveiseh area in Kordestan province. The plant was extracted using a four-step extraction method with increasing solvent polarity (i.e., hexane, dichloromethane, chloroform-methanol [9:1], and methanol). The methanol extract was finally separated between water and butanol. Hexane, dichloromethane, chloroform-methanol, butanol, and aqueous partitions were then subjected to cytotoxicity evaluation. Showing the most potent cytotoxic effects, the butanolic partition was further fractionated by medium-performance liquid chromatography and similar eluates were pooled to prepare five final butanolic fractions, named A–E. Results: In vitro cytotoxicity of these fractions against human cervical epithelioid carcinoma (HeLa) and human umbilical vein endothelial cell (HUVEC) was evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Fractions D, E, and A showed a significant and dose-dependent inhibition of cell proliferation (half maximal inhibitory concentration [IC50] of 30, 39.8, and 188.6 µg/mL, respectively). According to the preliminary thin-layer chromatography analysis, these cytotoxic effects may be mainly due to presence of saponin and flavonoid compounds. Conclusion: Future studies will be aimed to isolate and purify active constituents and investigate the effect of them on more different kinds of cancer cells.
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Ethanolic leaf extract of Ipomoea aquatica Forsk abrogates cisplatin-induced hepatotoxicity in albino rats p. 25
Elias Adikwu, Bonsome Bokolo, James Kemelayefa
DOI:10.4103/jrptps.JRPTPS_53_19  
Context: Hepatotoxicity is a therapeutic predicament that affects the clinical use of cisplatin (CPT). Ipomoea aquatica is traditionally used for the treatment of some diseases. This study examined the protective effect of the ethanolic leaf extract of Ipomoea aquatica (EEIA) against CPT-induced hepatotoxicity in albino rats. Materials and Methods: Fifty-four adult male albino rats randomized into nine groups (six rats in each group) were treated orally with EEIA (100, 200, and 400 mg/kg) daily for 7 days and CPT (6 mg/kg) intraperitoneally on day 5 and 7, respectively. On day 8, the rats were anesthetized; blood samples were collected and evaluated for plasma liver function markers. Liver samples were harvested and evaluated for biochemical parameters and histology. Statistical Analysis: Data are presented as mean ± standard error of the mean (SEM). Statistical analysis was performed using one-way analysis of variance (ANOVA) and Tukey’s test. Results: CPT-induced hepatotoxicity was characterized by significant (P < 0.001) elevations in liver and plasma levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transferase, total bilirubin, and conjugated bilirubin when compared to control. The alterations in liver redox status of CPT-treated rats were marked by significant (P < 0.001) decreases in superoxide dismutase, catalase, glutathione, and glutathione peroxidase levels with significant (P < 0.001) increases in malondialdehyde levels when compared to control. The liver of CPT-treated rat was characterized by hepatocyte necrosis. The hepatotoxic effect of CPT was significantly abrogated in a dose-dependent fashion in rats pretreated with EEIA 100 mg/kg (P < 0.05), 200 mg/kg (P < 0.01), and 400 mg/kg (P < 0.001) when compared to CPT-treated rats. Conclusion: EEIA has potential as treatment for CPT-induced hepatotoxicity.
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Anxiolytic and antidepressant effects of aqueous extract of Stachys lavandulifolia Vahl. in mice p. 31
Masoud Modarresi, Ahmad Mohammadi-Farani, Keyvan Amirshahrokhi, Rezvan Beheshtizadeh
DOI:10.4103/jrptps.JRPTPS_108_19  
Background: Stachys lavandulifolia Vahl. is a widely used plant in Iranian traditional medicine. It has long been used as an anxiolytic herb. The aim of this work was to investigate the anxiolytic and antidepressant properties of aqueous extract of aerial parts of Stachys lavandulifolia Vahl. in mice. Materials and Methods: For evaluation of anxiolytic and antidepressant effects of the plant, different doses (500, 1000, 1200, and 1400 mg/kg) of the extract were used in the mouse models of elevated plus maze (EPM) and forced swimming test (FST), respectively. The possible anxiolytic mechanism of the extract was determined by using pentylenetetrazol (PTZ) (10 mg/kg), propranolol (0.2 mg/kg), and atropine (0.5 mg/kg). Sedative effect of the extract was evaluated by ketamine sleeping time test, and rotarod was used to determine the effects of the extract on motor function. Statistical analysis was performed using one-way analysis of variance (ANOVA). Results: The results showed that the percentage of time spent and number of entries is significantly increased (P < 0.05) with doses of 1000 and 1200 mg/kg of the extract. PTZ but not propranolol or atropine reversed the effects of the extract (1000 mg/kg) on EPM. Neither doses of the extract could decrease the immobility of the mice in FST (P >0.05). Motor coordination was impaired (all doses) by the plant. Conclusion: This study confirms the anxiolytic properties of aqueous extract of S. lavandulifolia and suggests that its effects are mediated through GABAA receptors. The extract does not have sedative properties but the results are indicative of a coordination impairing potential of the extract.
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Improvement of antiproliferative activity of recombinant truncated form of Pseudomonas aeruginosa exotoxin (PE38) by vitamin E in MCF-7 cells p. 41
Fahimeh Baghbani-Arani, Vahid Asgary, Razieh Bigdeli, Rahele Najafi-Far, Atieh Hashemi
DOI:10.4103/jrptps.JRPTPS_114_19  
Background: In addition to beneficial roles of vitamin E in many metabolic processes and its antitumor activities, vitamin E derivatives have extensively been considered as permeability enhancers. Using these enhancers, permeability of a wide spectrum of drugs was reported to be significantly increased. PE38, a toxic substance with a potential application in cancer therapy, is a truncated form of Pseudomonas exotoxin A (PE), which lacks Ia and a portion of domain Ib. Objective: Here, the antiproliferative potential of PE38 and alpha-tocopherol (αT) form of vitamin E were assessed in MCF-7 cells. The role of vitamin E in PE38 cytotoxicity level was also evaluated. Materials and Methods: The antiproliferative potential of PE38, vitamin E, and a combination of them were colorimetrically evaluated in a cellular breast cancer model (MCF-7), using the MTT assay. P values of <0.05 were considered significant. Results: Compared to control cells, the PE38 inhibited the proliferation of MCF-7 cells (80% ± 1.37% cell viability) only at the highest concentration used (500 μg/mL) (P < 0.05). MTT assay also showed that 0.1, 1, and 10 mg/mL of vitamin E could significantly (P < 0.001) decrease the cell viability of MCF-7 cells to 57% ± 1.37%, 26.8% ± 1.37%, and 14.7% ± 1.37% at 24 h, respectively. Moreover, the coadministration of vitamin E (0.1 mg/mL) with 31.25, 62.5, 125, 250, and 500 μg/mL concentrations of PE38 decreases in cell viability from 100% in control cells to 35.61% ± 4.29%, 37.8% ± 6.45%, 36.42% ± 5.79%, 32.33% ± 4.62%, and 29.97% ± 5.07% at 24 h, respectively (P < 0.001). Conclusion: The results of this study suggest that vitamin E can enhance the antiproliferative activity of PE38 toward MCF-7 cells.
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Phytochemical analysis and evaluation of purified extract of Tinospora crispa stem for in vivo antihyperuricemic effect p. 46
Harwoko Harwoko, Warsinah Warsinah
DOI:10.4103/jrptps.JRPTPS_45_19  
Background: Tinospora crispa is used in folk medicines for the treatment of gout, rheumatoid arthritis, and internal inflammation. The presence of flavonoids, polyphenols, glycosides, and alkaloids in T. crispa stem is supposed to contribute to these therapeutic effects. This study aimed to analyze qualitative and quantitative phytochemical of purified extract of T. crispa stem (PETS) and to evaluate the in vivo antihyperuricemic effect. Materials and Methods: First, total flavonoid and total alkaloid contents of PETS were determined by colorimetric and gravimetric methods. After that, potassium oxonate-induced hyperuricemic mice were treated with three doses of PETS at 50, 100, and 200 mg/kg, and hydroalcoholic extract at 500 mg/kg. Moreover, allopurinol at 10 mg/kg and sodium carboxymethylcellulose 0.5% were orally administered as positive and negative controls, respectively. Serum uric acid levels were measured by ultraviolet–visible spectrophotometry. Results: The high flavonoids content (31.08% ± 1.77% rutin equivalent) in T. crispa stem possesses a potential as uricostatic in the treatment of gout. The purified extract of T. crispa stem at a dose of 100 mg/kg revealed a significant uric acid–lowering effect compared with negative control (P < 0.05). Conclusion: This study indicates the potential of T. crispa purified extracts in the treatment of hyperuricemia and gout.
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Comparative chemical evaluation of commercially available mint hydrosols produced in Fars province, Iran p. 52
Zahra Nazemosadat Arsanjani, Hamed Etemadfard, Mahmoodreza Moein
DOI:10.4103/jrptps.JRPTPS_17_19  
Background: Hydrosols of Mentha species are a common beverage among Iranians. The product quality may differ depending on the type of material used and the distillation process. However, despite the many investigations on the chemical composition of different mint essential oils, the co-produced hydrosols have rarely been evaluated. Objectives: This study evaluated and compared the chemical composition of 10 mint hydrosol samples purchased from local markets of Fars province, Iran, to Mentha piperita and Mentha spicata authentic hydrosols. Materials and Methods: Essential oils of the samples were extracted via liquid–liquid extraction by petroleum ether and analyzed using gas chromatography–flame ionisation detector (GC-FID) and gas chromatography–mass spectrometry (GC-MS). Hydrosols were then clustered based on their components. Results and Conclusion: Approximately 91.3%–100% of the components and overall 31 constituents were identified with the majority of oxygenated monoterpenes. Menthol, (R)-(−)-carvone, and piperitenone were the three different major compounds in the market samples. High percentages of menthol and carvone in many samples suggest that each product could be biologically active, and moreover, could be a valuable water-soluble source of their constituents. However, lack of chemical evaluation and standardization in this industry leads to inconsistency in quality and undermines the credibility of the industry.
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Chemical composition, antibacterial and antioxidant activities of Tagetes patula L. essential oil raised in Erbil, Iraq p. 59
Ausama A Safar, Anwar O Ghafoor, Dara Dastan
DOI:10.4103/jrptps.JRPTPS_68_19  
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.
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Evaluation of cytotoxic and apoptotic effects of DT386–BR2: A promising anticancer fusion protein p. 68
Fatemeh Shafiee, Mohammad Rabbani, Ali Jahanian-Najafabadi
DOI:10.4103/jrptps.JRPTPS_15_19  
Purpose: In the previous studies, we designed an anticancer immunotoxin containing the catalytic and translocation domains of diphtheria toxin fused to BR2, a buforin II-derived antimicrobial peptide as a cancer-specific cell penetrating peptide, in order to target various cancer cells. The aim of this study was to evaluate the in vitro cytotoxicity of DT386–BR2 against K-562 cells as the most famous cell line for leukemia. Materials and Methods: MTT and flow-cytometry assays were used for determining the cytotoxic effects and cell death mechanism of DT386–BR2, respectively, against K-562 cell line. The recombinant DT386 and synthetic BR2 were used as the negative control in cytotoxicity assay. Results: The results of this study showed a significant reduction in survival of K-562 cells caused by DT386–BR2 as compared with BR2 and DT386 fragments. On the contrary, the flow-cytometry results showed apoptosis induction by DT386–BR2 after 12h in a dose- and time-dependent manner. Conclusion: DT386–BR2 fusion protein can be used for further preclinical studies for determining its pharmacokinetic/pharmacodynamic profiles and evaluating its anticancer efficacy in suitable animal models.
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Clindamycin stewardship: An opportunity for hospitalized patients in Razi Hospital, Rasht, Iran p. 73
Shahram Ala, Afsoun Kamali, Razieh Avan
DOI:10.4103/jrptps.JRPTPS_74_19  
Background: In hospitalized patients, the most common used drugs are antibiotics. Programs designed to rational use of antibiotics improve the quality of care and infection management, and reduce costs. Aims and Objectives: The objective of this study was to assess the rational use of clindamycin in Razi Hospital, Rasht, Iran. Materials and Methods: This retrospective cross-sectional study was performed in Razi Hospital, Rasht, Iran. All hospitalized patients who received clindamycin were included. Patient’s demographic, duration of use and dose of clindamycin therapy, and other concomitant antibiotics were collected from patients’ medical records. Rational clindamycin prescribing was evaluated based on recommendations of UpToDate software, version 21.6, Waltham, MA, United States. Analysis of data was performed by the Statistical Package for the Social Sciences software, version 16.0. Results: A total of 607 patients receiving clindamycin during 15 months of study were evaluated. The mean age of the patients was 51.51 ± 15.92 years (range: 16–87 years). The most hospitalized patients receiving clindamycin were in internal ward (86%). The most frequently coadministered antibiotics with clindamycin were third-generation cephalosporins (47.9%). The majority of patients admitted in the winter (40.4%). The most frequently primary and final diagnosis in patients receiving clindamycin was reported pneumonia, respectively, 33.1% and 32.1%. Indication, dose, and duration of clindamycin were appropriate in 583 (96%), 277(47.5%), and 208 (35.7%) patients, respectively. Conclusion: The rate of incorrect dose and duration of clindamycin in our hospital were significantly high. Also, the majority of its prescription were as off-label indications. Programs for more justified administration of clindamycin to improve quality of care and decrease antibacterial resistance and cost are necessary.
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Assessment of antidiabetic activity of combination of Murraya koenigii leaves extract and Vitis vinifera seeds extract in alloxan-induced diabetic rats p. 79
Shreya M Palwankar, Pravin P Kale, Pramod K Kadu, Kedar Prabhavalkar
DOI:10.4103/jrptps.JRPTPS_50_19  
Background: Murraya koenigii is a well-known curry leaf tree. Its leaves are used as a spice in food recipe in India. Its related antidiabetic activity is attributed to alpha glucosidase activity of carbazole alkaloids. The proanthocyanidins present in Vitis vinifera contribute to its hyperglycemic activity through antioxidant effect and preservation of β-cell function. Aims and Objective: The aim of this study was to assess antidiabetic effect of the combination of M. koenigii leaves extract and V. vinifera seeds extract. Materials and Methods: A total of 36 animals were randomly selected for the study and were divided in six different groups: control group, alloxan (130 mg/kg; intraperitoneal [i.p.]) treated group, alloxan (130 mg/kg) treatment + M. koenigii leaves extract (300 mg/kg; per oral [p.o.]) treated group, alloxan (130 mg/kg) i.p. treatment + V. vinifera seeds extract (200 mg/kg; p.o.) treated group, alloxan (130 mg/kg) + M. koenigii leaves extract (150 mg/kg; p.o.) treatment + V. vinifera seeds extract (100 mg/kg; p.o.) treated group, and alloxan (130 mg/kg) treatment + glibenclamide (5 mg/kg; i.p.) treated group. Treatment was given for 21 days after induction of diabetes. Result: The combination treated group showed a significant reduction in serum glucose levels when compared to individual test extracts. It also attenuated the elevated activity of alkaline phosphatase enzyme in diabetic rats as compared with the healthy controls. The combination treatment showed reversal of the serum glutamic oxaloacetic transaminase (P < 0.001) and serum glutamic pyruvic transaminase (P < 0.001) levels. It also significantly decreased cholesterol level to near normalcy (P < 0.001). Conclusion: The findings of this study suggest additive antidiabetic effect of the combination of M. koenigii leaves extract and V. vinifera seeds extract.
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Knowledge, perception, and practice of pharmacy professionals on drug misuse and abuse in eastern region of Saudi Arabia p. 86
Dhfer M Alshayban, Royes J Chacko, Fatimah Aljishi, Jisha M Lucca
DOI:10.4103/jrptps.JRPTPS_34_19  
Background: Drug abuse is a worldwide issue affecting all human life aspects including health, social, economic, and security status. According to the United Nations Office on Drug and Crime reports, over 5% of adults used drugs at least once in the year 2015, and 29.5 million of them had consequences of inappropriate use of drugs. Information about severity of the problem in Saudi Arabia is limited, and therefore, a study was conducted among pharmacy staff to assess their knowledge, belief, and practice on drug misuse and abuse. Materials and Methods: A cross-sectional study was carried out in Eastern Province, Saudi Arabia. Pharmacy professionals with more than three months of experience were included in the study. A structured questionnaire was used to obtain participant's responses. Chi-square test was used to evaluate the association of sociodemographic factors with the participant's responses. Results: Ninety pharmacy professionals responded to this study. Overall 69 (76.7%) participants agreed that misuse and abuse are two different terms. Overall 48.9% (n = 44) of participants believed that the misuse or abuse of medications in Saudi Arabia is in an alarming situation. In addition, study showed different practices for patients who were suspected to be medication abusers. Conclusion: This study provided an initial picture about pharmacy staffs' knowledge and opinion regarding the misuse and abuse of medicines in Saudi Arabia. Participants' reactions and practices toward such behaviors were different and not consistent. Therefore, there should be a clear policy to define the role of the pharmacy staff toward the misuse and abuse of medication in Saudi Arabia.
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Angiotensin-converting enzyme and renin inhibition activities, antioxidant properties, phenolic and flavonoid contents of Cuphea ignea A. DC p. 92
Walaa M Ismail, Shahira M Ezzat, Haidy E Michel, Kadriya S El Deeb, Ahlam M El-Fishawy
DOI:10.4103/jrptps.JRPTPS_81_19  
Cuphea ignea A. DC. is an ornamental plant belonging to family Lythraceae distributed in the tropics and temperate zones. Some Cuphea members are traditionally used in treatment of hypertension. The aim of this research was to study the antihypertensive activity of the plant by applying a bio-guided fractionation scheme of the leaves, stems, and flowers using in vitro angiotensin-converting enzyme (ACE) and renin inhibition assays to identify the active organ and its respective active fractions. The aqueous extract and the n-butanol fraction of the leaves showed the highest ACE inhibition activity with IC50 values 0.491 and 0.084 mg/mL, respectively. The renin inhibition activity showed that the alcoholic extract of the leaves had the highest percentage of inhibition (94.82%). Meanwhile, the methylene chloride fraction of the stems showed the highest renin inhibition activity (98.14%) followed by the ethyl acetate fraction of the leaves (93.09%). The antioxidant activity was tested using the 2,2-diphenyl-1-picrylhydrazyl and oxygen radical absorbance activity assays. Correlation studies of the antioxidant activity showed moderate correlation with the phenolic content and strong correlation with the flavonoid content. The renin inhibition activity showed significant positive correlation with the phenolic and flavonoid contents with r values (0.777 and 0.629, respectively).
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Comparison of green tea and metformin effects on anthropometric indicators in women with polycystic ovarian syndrome: A clinical trial study p. 97
Maryam Farhadian, Somayeh Barati, Minoo Mahmoodi, Amir Barati Mosleh, Mahnaz Yavangui
DOI:10.4103/jrptps.JRPTPS_14_19  
Background: Polycystic ovary syndrome (PCOS), as a complex reproductive and endocrinological disorder, affects up to one in five women. Treatment for obesity in women with this syndrome is necessary due to the occurrence of various complications, especially infertility. Recently, green tea with many health benefits, as a natural herbal medicine, has been widely considered in treating various diseases. Objective: This clinical study was planned to compare the effect of green tea and metformin treatment on the anthropometric indices of women with PCOS. Materials and Methods: In this double-blind, randomized clinical trial, 45 women among 18–35 years of age with PCOS referring to the endometriosis center of Fatemieh Hospital of Hamadan, Iran, who had the eligibility criteria for entering the study, were randomized into three study groups: the green tea, the metformin group, and the control group. Weight, body mass index (BMI), waist circumference, hip circumference, and waist-to-hip ratio, before, 1 month later, and 3 months after intervention in each group were measured. Data were statistically analyzed using Statistical Package for the Social Sciences (SPSS) statistical software, version 23.0. Results: No statistically significant difference was observed between the three groups during the study period. A significant reduction of anthropometric indices, such as weight, BMI, waist, and hip circumference, was observed in the green tea group. Conclusion: The use of green tea for patients with PCOS is recommended as a complementary therapy that can have potential effects on obesity.
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Antibacterial effect of combination of cinnamon essential oil and thymol, carvacrol, eugenol, or geraniol p. 104
Yassine El Atki, Imane Aouam, Amal Taroq, Fatima El Kamari, Mohammed Timinouni, Badiaa Lyoussi, Abdelfattah Abdellaoui
DOI:10.4103/jrptps.JRPTPS_25_19  
Bacterial resistance to classic antibiotics is an alarming rate to put this into control with the use of natural products of plant derivatives. The objective of this study was to determine the phytochemical of cinnamon essential oil (EO) and to evaluate its antibacterial activity alone and in combination with some main components of EOs such as thymol, carvacrol, eugenol, or geraniol against three bacterial strains (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa). The phytochemical analysis of cinnamon EO was evaluated using gas chromatography-flame ionization detector and gas chromatography-mass spectrometer analysis. The antibacterial activity of tested compounds was determined by agar disk diffusion and minimum inhibitory concentration (MIC) assays. The checkerboard method was used to quantify the efficacy of cinnamon EO in combination with those compounds. The results showed that the major compound in the cinnamon EO was trans-cinnamaldehyde (91.01%). Cinnamon oil was the highest antibacterial activity with MIC of 0.005, 0.005, and 0.02 mg/mL against E. coli, S. aureus, and P. aeruginosa, respectively. Synergistic activity was shown only against S. aureus by the combination of cinnamon EO and thymol. The additive effect was found against E. coli when cinnamon EO was combined with thymol or carvacrol, and against S. aureus when cinnamon EO was combined with carvacrol. However, the combination of EO and thymol or carvacrol showed an indifference action against P. aeruginosa. The combination of cinnamon EO with thymol or carvacrol can be used as an alternative therapeutic agent for medical application and as a natural preservative.
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Daily oral vitamin D3 regimen in similar cumulative doses is more effective than weekly oral vitamin D3 regimen in patients with vitamin D deficiency p. 110
Romina Hamedooni-Asl, Firozeh Sajedi, Younes Mohammadi, Mahtabalsadat Mirjalili, Ehsan Mirzaei, Azadeh Eshraghi, Maryam Mehrpooya
DOI:10.4103/jrptps.JRPTPS_73_19  
Context: Vitamin D deficiency is a common health problem worldwide, especially in the Middle Eastern region. Although various dosing regimens of vitamin D have been used for the treatment of vitamin D deficiency, it is still unclear as to which dosing regimen can efficiently increase the serum level of vitamin D in different patient population. Aim: This study was designed to compare the efficacy of weekly and daily regimens of vitamin D3 in patients with vitamin D deficiency. Settings and Design: A randomized clinical trial was conducted in the autumn and winter of 2016 and 2017, Hamadan, Iran. Materials and Methods: A total of 130 patients with moderate to severe hypovitaminosis D were allocated into two groups: weekly 50,000 IU (routine recommended dose for vitamin deficiency treatment) or daily 4,000 IU (safe upper limit dose of vitamin D per day) of oral vitamin D3 for 8 and 14 weeks, respectively. The serum levels of 25-OH-vitamin D were measured in all patients at baseline and at the end of the treatment period. Results: Results of this study showed that though both dosing regimens can be effective in increasing the serum level of 25-OH-vitamin D, higher percentage of the subjects in the daily regimen group achieved the sufficient serum level of 25-OH-vitamin D when compared to the weekly regimen group. Conclusion: Accordingly, probably owing to better bioavailability of daily regimen of vitamin D3 and establishment of a more steady serum concentration compared with weekly regimen, it can be recommended as the preferred dosing regimen for effective treatment of vitamin D deficiency.
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Chemical composition, antioxidant, antibacterial, and anticancer activities of scorzonera calyculata boiss. and centaurea irritans wagenitz. Extracts, endemic to iran p. 118
Anahita Ayromlou, Shiva Masoudi, Amir Mirzaie
DOI:10.4103/jrptps.JRPTPS_97_19  
Background & Purpose: This research focused on the composition for the essential oils, which was obtained by solvent-free microwave extraction (SFME) from the aerial parts of Scorzonera calyculata, and hydrodistilled oils from the aerial parts and roots of Centaurea irritans, from Astraceae family, were investigated by gas chromatography (GC) and GC/mass spectrometry (MS). In addition, the biological activities of the methanolic extracts from the aerial parts of S. calyculata and C. irritans were determined. Methods: Total phenolic content was determined by the Folin–Ciocalteu procedure. Antibacterial activity of the methanolic extracts was carried out by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Cytotoxicity of the methanolic extract of S. calyculata against human lung cancer cells (A549) and the methanolic extract of C. irritans against breast lung cancer cells (MCF-7) were measured using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Results: The obtained results of GC/MS technique showed that the SFME oil of S. calyculata, was rich in regard to nonterpenoid and sesquiterpene components. Both oils from the aerial parts and roots of C. irritans were rich in regard to oxygenated monoterpenes. The S. calyculata and C. irritans extracts showed moderate antioxidant activities with an inhibitory concentration (IC50) value of 1.48 and 1.99 mg/mL, using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and 73.51 and 44.48 μmol Fe (II)/g dry mass using ferric-reducing antioxidant power (FRAP) assay, respectively. The extracts showed high toxicity against gram-positive bacteria and the IC50 value of extracts cytotoxicity was found to be 9.8 and 10.3 mg/mL, respectively. Conclusion: It appeared that the investigated samples could be as a promising drug for pharmaceutical industry.
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Synthesis and cytotoxicity evaluation of N-(5-Mercapto-4H-1,2,4-triazol-3-yl)-2-phenylacetamide derivatives as apoptosis inducers with potential anticancer effects p. 128
Ahmad Mohammadi-Farani, Hosna Sadat Zamani Mousavi, Amin Hosseini, Alireza Aliabadi
DOI:10.4103/jrptps.JRPTPS_57_18  
Background: Discovery of new anticancer drugs is one of the urgent issues in the medicinal chemistry researches. Incidence of severe side effects and acquired resistance to the current medications are the logical reasons for the development of novel antineoplastic agents. Methods: Herein, a new series of 4H-1,2,4-triazole derivatives was synthesized and subsequently their cytotoxicity was assessed using dimethylthiazol diphenyltetrazolium bromide assay. Furthermore, activity of caspase 3, mitochondrial membrane potential (MMP), and generation of reactive oxygen species (ROS) were investigated. All synthesized derivatives (3a–3o) were tested against Hela (cervical cancer), A549 (lung carcinoma), and U87 (glioblastoma), and the obtained data were compared with doxorubicin. Results: Among the chlorinated derivatives, compound 3c with para positioning of the chlorine on the phenyl residue possessed higher cytotoxicity (IC50 = s3.2 ± 0.6 μM) than compounds 3a and 3b, which positioned chlorine at ortho and meta position, respectively. Chlorine as electron-withdrawing moiety caused enhancement in cytotoxicity. Conclusion: Fortunately, most of the tested compounds showed remarkable cytotoxic activity toward applied cells, especially Hela. Activation of caspase 3, MMP reduction, and ROS generation were also observed for the studied compounds.
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REVIEW ARTICLES Top

A review on analytical methods of antigout agents p. 136
Ramanlal N Kachave, Pragati B Mandlik, Snehal R Wakchaure
DOI:10.4103/jrptps.JRPTPS_32_19  
The aim of this study was to provide information of the development in analytical perspective of impurity profiling, force degradation, and bioanalysis of pharmaceutical drug substance and drug products used for the treatment of gout. This information was discussed on the basis of year of publication, matrix (active pharmaceutical ingredient, dosage form, and biological fluid), sample preparation technique, column and types of elution in chromatography (isocratic or gradient), detector, and therapeutic categories of drug, which were used for analysis. It focuses mainly on analytical methods including hyphenated techniques for the identification and quantification of impurity, degradants, and metabolites in different pharmaceutical and biological matrices.
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Drug delivery through nose: A noninvasive technique for brain targeting p. 168
Abhishek Thakur, Pankaj K Singh, Swadhin S Biswal, Navneet Kumar, Chandan B Jha, Gurvinder Singh, Charanjit Kaur, Sheetu Wadhwa, Rajesh Kumar
DOI:10.4103/jrptps.JRPTPS_59_19  
Majority of drugs are usually introduced through oral or intra-venous route for fast action, better patient compliance and ease of drug administration. However, the low bioavailability and limited brain exposure of orally administered drugs pose a huge challenge to treat neurodegenerative and psychiatric disorders. So, the situation demands for targeting the drug to brain. For brain targeting, a number of factors are considered viz. molecular weight, route of administration, lipophilic character of drug and blood brain barrier (BBB). These factors limit the movement of drug into brain tissue through BBB. To overcome these problems, intranasal drug administration is one of the promising routes that bypasses BBB and cuts down the dose to be administered with better brain exposure to drug. Nasal route has been used for the administration of antihistamines, local analgesics and corticosteroids intended for local drug delivery in nasal allergy, nasal congestion and nasal infection. However, systemic drug delivery through this route has also been explored in recent times. For nose to brain drug delivery, olfactory and respiratory region are utilized which also enable delivery of larger molecules to reach brain tissues. Such delivery systems are generally pH or temperature dependent. Certain diseases of nervous system like migraine, dementia, parkinsonism, epilepsy and Alzheimer’s disease can be successfully treated through this route. This review attempts to highlight the anatomy of nose, mechanisms of drug delivery from nose to brain, critical factors in the formulation of delivery systems, nasal formulations and applications of nasal route for delivery of various drugs.
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