Research/Original Articles

Evaluation of immune responses induced by hydroalcoholic extract of Allium ampeloprasum. L subsp iranicum in mice

Farideh Shiehzadeh , Parham Vakili, Kobra Shirani

Iranian Journal of Pharmaceutical Sciences, Vol. 18 No. 3 (2022), 1 July 2022, Page 176-182

The extract of some plants can play a role in modulating the function of the human immune system. Several studies have shown that Allium species can stimulate the immune system through different cellular mechanisms. In this study the effect of the hydroalcoholic extract of Allium ampeloprasum. L subsp iranicum on the immune responses of NMRI mice was investigated. Mice were randomly divided into three groups and each group was divided into four subgroups: normal saline, levamisole (20 kg/mg), A. Iranicum (150 kg/mg), and A. Iranicum (300 kg/mg). To evaluate immune responses, body and spleen weight, white blood cell count, delayed hypersensitivity response (DTH), antibody titer (HA), and lymphocyte proliferation test were used.

A. Iranicum provoked several parameters including spleen weight, spleen cellularity, proliferation response to lipopolysaccharide (LPS) and phytohemagglutinin-A (PHA), HA titer, and DTH response. While A. Iranicum did not affect body weight and white blood cell counts. Considering the obtained results, it seems that the A. Iranicum can play an effective role in activating the immune system. To better understand the effect of the A. Iranicum on different cellular mechanisms of the immune system, further research is needed.

Inequitable distribution of health resources leads to high costs and sustainable poverty for households. Therefore, it is necessary to study distribution in health. The most common indicator for measuring inequality is the Gini coefficient. Therefore, the present study was conducted to measure and analyze inequality in the distribution of various pharmacies using the Gini coefficient and the Lorenz curve in Iran. This research was a retrospective cross-sectional study that looked at the state and trend of inequality in the distribution of various types of pharmacies in 11 Lorestan cities from 2016 to 2021. Data was gathered from various data centers. Finally, the Gini coefficient and the Lorenz curve were determined. Excel was utilized in this project. The results study showed an increase in the Gini coefficient of the total pharmacies in Lorestan province (0.436) which is relatively indicative of the unfair distribution of the pharmacies but this value is higher for private pharmacies (0.545). The Gini coefficient of public pharmacies was (0.377) and for rural pharmacies was (0.282). So, to achieve an appropriate level of justice in the distribution of pharmaceuticals and pharmacies, resources should be distributed according to the requirements of city residents. Different kinds of pharmacies should be considered for different population groups when developing policies.

Antioxidant Effects of Amino Acids-Capped Silver Nanoprisms Against Cadmium-Induced Toxicity

Sarwar Allah Ditta, Atif Yaqub, Arslan Haider, Fouzia Tanvir, Muhammad Rashid

Iranian Journal of Pharmaceutical Sciences, Vol. 18 No. 3 (2022), 1 July 2022, Page 192-213

The surface functionality of nanomaterials (NMs) with suitable biomolecules may enhance their biocompatibility and make them more effective for biological applications. Furthermore, the functionalization of various materials with biomolecules would also yield more secure and biocompatible nanomaterials for different applications. The present research was designed to evaluate the amino acids-based surface functionality of silver nanoprisms (AgNPrs). Silver nanoprisms were prepared by chemical method and further capped with amino acids such as L-cystine (Cys), L-glycine (Gly), and L-tyrosine (Tyr). Characterization of the newly-synthesized NMs was performed by using various techniques. Prepared nanomaterials (NMs) were assessed for their in vitro antioxidant activity using diphenylpicrylhydrazyl (DPPH), ferric reducing power (FRP), and hydrogen peroxide (HP) scavenging assays. In vivo, the antioxidant potential of the same was evaluated in the cadmium-intoxicated Mus musculus model. Tyr-AgNPrs (p < 0.05), Cys-AgNPrs (p < 0.05), and Gly-AgNPrs (p > 0.05) showed enhanced DPPH scavenging activity. Whereas the Cys-AgNPrs displayed enhanced FRP activity and Tyr-AgNPrs displayed enhanced HP scavenging activity. The AgNPrs and cadmium-exposed mice displayed a decreased (p<0.05) catalase (CAT) activity in G2 and G3, whereas it increased in G4. The superoxide dismutase (SOD) activity was decreased in the G2 (p < 0.05) and G5 (p > 0.05) groups, whereas it increased in the G3 (p < 0.05), G4, and G6 groups of mice. The G2 showed a slightly decreased glutathione-s-transferase (GST) activity (p > 0.05). The levels of reduced glutathione (p<0.05) and metallothioneins (p>0.05) were elevated in the cadmium-intoxicated group. The results revealed that the cystine-AgNPrs and tyrosine-AgNPrs demonstrated higher antioxidant potential in comparison to other treatments. It is concluded that biomolecule-conjugated AgNPrs can work efficiently with more biocompatibility for various nanotechnological and biomedical applications.

In vitro antimalarial activity of the biosurfactant produced by Serratia marcescens MBC1

Achmad Arifiyanto, Endah Setyaningrum, Ni'matuzahroh Ni'matuzahroh

Iranian Journal of Pharmaceutical Sciences, Vol. 18 No. 3 (2022), 1 July 2022, Page 214-222

Serratia is a bacterium with a distinctive red-pigment prodigiosin, known as a plasmodium growth inhibitor. This species is also known for its reliability as a producer of biosurfactants. Furthermore, the ability of these bacteria to reduce the interface tension in antimalarial activity has not been reported. Therefore, this study aimed to develop biosurfactants as antimalarial drugs candidate. Additionally, tryptone Soy Broth is used as a fermented media to produce biosurfactants with the addition of Serratia marcescens MBC1. Biosurfactant activity was evaluated on a hydrocarbon substrate consisting of used motor lubricants, used-cooking oil, and diesel. Emulsifying activity, oil spread test, blue agar, and infrared spectroscopy were methods used for evaluating biosurfactants. Used motor lubricants produced the highest emulsification index at 41.40%. Spectroscopic results using Fourier-transform infrared spectroscopy (FTIR) revealed that the compounds contain glycolipids and lipopeptides. The antimalarial test using Plasmodium falciparum d37 obtained an inhibitory concentration 50 of 3.66 µg/mL. There was limited information on the toxicity of biosurfactants in cells of Plasmodium parasites. The use of biosurfactants from Serratia marcescens MBC1 to control plasmodium infection needs to be improved to provide an alternative to malaria control from natural ingredients.

Population Pharmacokinetic Study of Gabapentin in Iranian Healthy Volunteers

Masoumeh Kurd, Tayebeh Esmaeili, Katayoun Derakhshandeh

Iranian Journal of Pharmaceutical Sciences, Vol. 18 No. 3 (2022), 1 July 2022, Page 223-234

The objective of the study was to evaluate the pharmacokinetics of a single oral dose of 300 mg gabapentin capsule in an Iranian healthy population. The study was a standard two-way, crossover, randomized, and single-dose study with one-week washout period in 24 healthy volunteers who received 300 mg gabapentin capsules (test and reference formulation). After drug administration, blood samples were taken according to the planned times over a period of 24 hours. The plasma concentrations of gabapentin were determined using the validated high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. All the pharmacokinetic parameters for gabapentin in healthy volunteers were calculated using nonlinear mixed-effect modeling and standard non-compartmental methods. A one-compartment model with a first-order absorption rate and first-order elimination rate with a proportional error model described the pharmacokinetics of gabapentin. Values (relative standard error (RSE) %) for first-order absorption rate constant (Ka), oral clearance (Cl/F), and apparent volume of distribution (Vd/F) were 1.08 (7.23) 1/h, 6.72(0.29) L/h, and 73.82(5.10) L. The mean estimate for non-compartmental pharmacokinetic parameters including maximum plasma concentration (Cmax), the area under the curve to the last quantifiable concentration (AUCt), and the area under the curve to the infinity (AUCinf) was calculated. Cmax for test and reference formulation was 3850 ng/mL and 3856 ng/mL respectively. The AUCt for test and reference formulation was 39549 ng. h/mL and 40249 ng. h/mL respectively. The AUCinf for test and reference formulation was 47161 ng. h/mL and 633424 ng. h/mL respectively. The median (range) for the time to peak plasma gabapentin concentration (Tmax) for the test and refer­ence drug was 3 (1.5-6) hours and 3 (1.5-5) hours respectively. The mean (standard deviation) elimination half-life (t1/2) of gabapentin for the test and reference drug was 9.39 (2.75) hours and 8.88 (2.48) hours. They were all within the acceptable range of 80-125%, consequently, we concluded that the two gabapentin formulations were bioequivalent. Our results confirmed that the gabapentin pharmacokinetic model in the Iranian healthy population was similar to other studied populations. However, we could not find any influential covariate to explain the inter-individual variability of parameters.

This study evaluated the amounts of lead (Pb), cadmium (Cd), and manganese (Mn) in pediatric over-the-counter medications made in Uganda. Twelve distinct brands from four categories of pediatric medications (antihistamine, cough expectorant, antipyretic and analgesic, and cold and flu medication) were chosen at random from Kampala's drug stores. Before acid digestion, the syrups were washed with concentrated HNO3:HClO4 (5:1), and the metals were measured using FAAS AAnalyst 400. The average values (µg/mL) found were as follows: antihistamine (Cd, 0.89±0.122; Pb, 7.01±10.0); cold and flu (Cd, 0.89±0.073; Pb, 1.69±0.718); cough expectorant (Cd, 0.14±0.0196; Pb, 1.55±1.332); and antipyretics and analgesic (Cd, 0.16±0.774; Pb, 1.76±1.123). Antihistamines and medications for the cold and flu were not detectable in sample codes (A1 and B1), respectively. In every sample examined, manganese levels were below the non-detectable threshold. The different coefficient of variation (CV) values found in this investigation demonstrated that the metals in pediatric medications came from a wide variety of sources. According to total metal content, each brand of pediatric medication contains Antihistamine (56%), Antipyretic and analgesic (15%), Cold and flu (15%), and Cough expectorant (14%). Uganda's pediatric medicine producers should be closely watched by the National Drug Agency.

Evaluation of the effect of Medicago sativa on Lipid Profile and Iron Indices in Healthy Volunteers

Maria Tavakkoli Ardakani, Fatemeh Agah, Faraz Mojab

Iranian Journal of Pharmaceutical Sciences, Vol. 18 No. 3 (2022), 1 July 2022, Page 244-252

Medicago sativa (alfalfa) has a long history of traditional use. Several studies indicate that the ingestion of M. sativa reduces cholesterol absorption and atherosclerotic plaque formation in animals and has been reported to be beneficial in the treatment of hemorrhage, as a tonic after blood loss and during anemia. Because hypercholesterolemia is an important risk factor for heart diseases and anemia is a common problem in developing countries, this double-blind, placebo-controlled, randomized clinical trial was designed to evaluate the effect of alfalfa extract on lipid profile and iron indices in healthy volunteers. 19 volunteers (all male) with an average age of 35 were elected for a randomized double-blind study. These volunteers were divided into two groups for drug (9 males) and placebo (10 persons). The capsules of 250 mg were taken three times a day for two months. Blood samples were collected at baseline, one month, and two months after taking the capsules. Ferritin, TIBC (Total Iron Binding Capacity), Iron, CBC (Complete Blood Count), cholesterol, triglyceride, LDL, and HDL were determined by laboratory testing standards. After two months in the treated group, serum iron showed more increase and TIBC factor decreased more in comparison with the control group and their LDL and triglyceride decreased and HDL increased but was not statistically significant. Alfalfa ethanolic extract, with 750 mg/day can help decrease LDL and triglyceride and increase HDL, and maybe increase serum iron as an adjunctive for hypercholesterolemia and anemia treatment.

Possible Rapid Therapeutics for SARS Coronavirus 2 RNA-dependent RNA polymerase: A Systematic Review

Vahid Asghariazar, Kamyar Mazloum Jalali, Ali Aghebati-Maleki, Somayeh Biparva Haghighi, Negin Balar, Hadi Peeri-Dogaheh, Chiman Karami

Iranian Journal of Pharmaceutical Sciences, Vol. 18 No. 3 (2022), 1 July 2022, Page 253-264

Research confirms that viral polymerases play a key role in viral genome replication and transcription. Hence, they are essential for the multiplication and survival of viral particles. Our review is limited to original papers in the English language from 2019 to 2020 using various databases, including PubMed, Scopus, Google Scholar, and Science direct. Out of 159 papers, 27 drugs may effectively prevent RNA-dependent RNA polymerase (RdRP), of COVID-19, agreed in order of drug discovery years and paper publication, respectively. In this paper, we realized that the structure comparison and sequence alignment suggest that the mode of substrate RdRP is highly conserved in diverse RNA viruses, providing a foundation for designing broad-spectrum antiviral drugs based on nucleotide analogs.