Pharmaceutical Sciences

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 Journal of Reports in Pharmaceutical Sciences 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.

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 Journal of Reports in Pharmaceutical Sciences 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.

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 Journal of Reports in Pharmaceutical Sciences 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.

Antioxidant activity and phytochemical screening of Ficus benghalensis aerial roots fractions Zeinab Etratkhah, Seyed Esmaeil Sadat Ebrahimi, Nafiseh Khosravi Dehaghi, Yousef Seifalizadeh Journal of Reports in Pharmaceutical Sciences 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.

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 Journal of Reports in Pharmaceutical Sciences 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.

Evaluation the effect of nicotine injection on the lungs of mice Bushra Jasim Mohammed, Amina Naama Al-Thwani Journal of Reports in Pharmaceutical Sciences 2019 8(1):34-38 Background: Nicotine is the chief addictive substance in cigarette smoking which conceder as the main cause of mortality worldwide. Aims: Through the current in vivo study, we tried to evaluate the harmful effect of nicotine injection on the lungs of mice. Materials and Methods: A total of 40 healthy male mice were divided into four groups of 10 mice each, injected subcutaneously with 0.1 ml of (1 mg/kg) nicotine for 5 days a week for (8, 12, and 16) weeks, whereas the control group injected with 0.1 ml of normal saline. The mice were sacrificed, lungs were isolated and divided into two parts, the first for measurement malondialdehyde (MDA) and glutathione (GSH), the second was subjected to histopathological examination. Results: The results showed that the levels of MDA were significantly elevated (P ≤ 0.01) in all work groups and the mice of Group D had the highest MDA value (23.13 ± 3.4 nmol/ml) with statistically significant difference (P ≤ 0.01), and GSH levels were significantly decreased (P < 0.01) in all workgroups, the Group D had the lowest value (6.77 ± 1.33 mM/ml) with statistically significant difference (P ≤ 0.01), also the results clarified that nicotine injection was caused a pathological effect in mice lung tissues such as alveoli damage and emphysema, congestion of blood vessels, hemorrhage, alveolar edema, lung fibrosis, lymphocytes infiltration, and these effects were graded in terms of severity depending on the injection period of nicotine. Conclusion: It can be concluded that the nicotine injection causes significant changes in lung tissues and oxidant markers levels (MDA and GSH).

A prospective study on the burden of renal replacement therapy and pattern of comorbidities among chronic kidney disease patients in clinical practice Olumuyiwa John Fasipe, Peter Ehizokhale Akhideno, Oluwatosin Beatrice Ibiyemi-Fasipe Journal of Reports in Pharmaceutical Sciences 2019 8(1):39-46 Background: The high rate of renal replacement therapy, respective clinical staging, and pattern of associated specific comorbidities/complications among chronic kidney disease (CKD) patients can influence and predispose them to increase morbidity, mortality, and health-care cost. In addition, there could also be a prolongation in the length of hospital stay and recurrent frequency of hospitalization. Aim: This study was predominantly designed to highlight and create awareness concerning the burden of renal replacement therapy and pattern of associated specific comorbidities/complications among CKD patients in renal practice. Materials and Methods: This was a descriptive, prospective study of 18-month duration that was carried out to review the medical case records of consented adult CKD patients attending a Nigerian Tertiary Kidney Care Hospital from January 2015 to June 2016. Results: This study involved 123 consented adult CKD patients made up of 82 (66.67%) males and 41 (33.33%) females with a mean age of 53.81 ± 16.03 years. Eighty-six (69.9%) of the patients were in CKD Stage 5, 15 (12.2%) were in CKD Stage 4, 19 (15.5%) were in CKD Stage 3, 2 (1.6%) in CKD Stage 2, and the remaining one (0.8%) in CKD Stage 1. Regarding the form of nephrological interventions offered, majority of the respondents, i.e. 66 (53.66%) were on maintenance dialysis, followed by 53 (43.09%) on conservative care, while 4 (3.25%) were on renal graft transplant. Among these CKD patients, the prevalence of renal replacement therapy was 56.91%. Most proportion of the respondents 45 (36.59%), were having two number of comorbidities with hypertension 103 (83.70%), diabetes mellitus 39 (31.70%), obesity 24 (19.51%), heart failure 11 (8.90%), obstructive uropathy 8 (6.50%), human immunodeficiency virus (HIV) infection 7 (5.70%), and stroke 5 (4.10%) being the most frequent. Conclusion: The prevalence rates for renal replacement therapy, hypertension, diabetes mellitus, and obesity were significantly high among these CKD patients. In this study, the high rate of renal replacement therapy, respective clinical staging, and pattern of associated specific comorbidities/complications among these CKD patients may significantly increase the risk of morbidity, mortality, recurrent frequency of hospitalization, length of hospital admission, and health-care costs.

Milk-based oral formulations of ibuprofen: An investigation on the role of milk in improving dissolution rate of drug Sukhmeet Singh Kamal, Daljit Kaur, Parminderjit Kaur, Amit Sharma, Ashish Kumar Garg, Charanjit Kaur, Gurvinder Singh, Rajesh Kumar Journal of Reports in Pharmaceutical Sciences 2019 8(1):47-54 Introduction: More than 40% of the newly developed drugs pose a problem of aqueous insolubility which is a major challenge for pharmaceutical scientists since in this form; drug doesn't show required bioavailability and hence sufficient therapeutics effect. Objective: The improvement of dissolution rate of ibuprofen (IBF) (poorly water-soluble drug) by formulating its solid dispersions using milk as generally recommended as safe carrier was the goal and purpose of this study. Method: For this, milk containing 1.5% fat (named yellow milk due to yellow-colored pack) and milk containing 4.5% fat (named green milk due to green-colored pack) were used. Initially, both types of milk were rota evaporated to obtain free flowing powdered form. Then, the physical mixtures were prepared in different ratios by simple mixing and solid dispersions were formulated in different ratios by solvent evaporation method using hot air oven. Various techniques were used to evaluate and characterize the physical mixtures and solid dispersions, which included melting point determination, solubility studies, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy, X-ray diffraction (XRD), in vitro dissolution studies, and scanning electron microscopy (SEM). Results: DSC and XRD studies showed reduction in peak intensity of drug indicating the conversion of crystalline drug into amorphous form. SEM studies indicated that the agglomerates formed were smaller and denser with a smooth surface. In vitro dissolution studies showed that the quantity of drug solubilized and the rate of dissolution increase after formulation into the solid dispersions. Conclusion: The milk powder was found to enhance the solubility of IBF due to the presence of casein which entrapped the hydrophobic drug by forming micelles.

Role of pea protein hydrolysates as antinephrotoxicity Meilinah Hidayat, Sijani Prahastuti, Teresa Liliana Wargasetia, Vincentius Ferdinand, Roro Wahyudianingsih, Andreanus Andaja Soemardji, Siti Farah Rahmawati, Nova Suliska, Khomaini Hasan Journal of Reports in Pharmaceutical Sciences 2019 8(1):55-60 Introduction: Renal damage can be caused by various causes. One of them is drugs that are toxic to the renal, such as cisplatin (CP). In an attempt to find a remedy for antinephrotoxicity, several hydrolyzed proteins were investigated. This study was conducted to find out the effects of 8 peas protein hydrolysates (PPH) hydrolyzed using simple procedure to renal organ indexes (OIs) and histopathological features of CP-induced nephrotoxicity Wistar rats. Materials and Methods: Protein hydrolysates of yellow peas, gude beans, green peas, and pea protein isolate (PPI) which hydrolyzed using neutrase or bromelain were administered to 50 female Wistar rats. The treatments were given for 30 days, and on day 7, all groups of rats, except negative control group, were injected CP intraperitoneal. Renal OIs were measured and kidneys were histopathological analyzed, which the results were converted to scoring system. Data were analyzed using ANOVA, LSD, Kruskal–Wallis, and Mann–Whitney test. Results: Data of renal OIs were homogenous and normally distributed but were not significantly different between groups (P > 0.05).The nephrotoxicity of CP were not changing the renal OI but worsen the histopathological features of renal tubules in CP-induced rats (P < 0.01). All protein hydrolysate treatment groups showed less histopathological score than CP group. Green PPH hydrolyzed by bromelain-treatment group showed the lowest scores. Conclusion: All PPH hydrolized with neutrase or bromelain improve the CP-induced nephrotoxicity rats. Green PPH with bromelain hydrolyzed had a promising potency as antinephrotoxicity.

Antioxidant activity of the Ferula gummosa Boiss.'s aerial parts: Measurements based on different assay methods Abdoreza Nazari, Elham Golezar, Hamid Mahdiuni Journal of Reports in Pharmaceutical Sciences 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.