Iranian Journal of Pharmaceutical Sciences

This study employed a multifaceted computational approach to identify potential inhibitors of aquaporin 3 (AQP3) derived from phytochemicals found in the Santalum album as potential drug candidates for melanoma treatment. Initially, the AQP3 structure was modeled using SWISSMODEL, which yielded a satisfactory GMQE score of 0.70 and a MolProbity score of 1.61. The QMEAN Z-score (-3.29) indicated acceptable quality, and Ramachandran analysis revealed that 95.12% of the residues were within the favored region. Virtual screening of phytochemicals utilized AutoDock Vina to identify compounds with strong binding affinity for AQP3. Phytochemicals exhibiting docking scores of -7 or less were selected for further analysis. The physicochemical properties and drug-likeness were evaluated using SWISS ADME, revealing compounds with favorable solubility, permeability, and gastrointestinal absorption. Biological activity prediction through the PASS web server indicated significant probabilities of dermatologic and antineoplastic activities for selected compounds. ADME/T properties were analyzed using the ADMET Lab 2.0 server, demonstrating favorable pharmacokinetic characteristics and safety profiles for compounds such as alpha-bergamotenol, himachalol, lupeol, levomenol, and sclareol. Except for himachalol, the other phytochemicals showed good safety profiles. Apart from himachalol, the remaining phytochemicals demonstrated favorable safety profiles. Molecular dynamics (MD) simulations provided insights into the stability and flexibility of receptor-ligand complexes over time, with compounds such as sclareol and levomenol exhibiting stable interactions. This comprehensive computational investigation highlights the potential of phytochemicals from S. album, particularly levomenol and sclareol, as inhibitors of AQP3. Further experimental validation is necessary to explore their clinical application in treating dermatologic conditions and cancer.

The COVID-19 pandemic has significantly affected people's lives and healthcare systems worldwide. Therefore, it is important to determine its effects on the economic and health sectors. This study aimed to calculate and analyze the costs and outcomes of COVID-19 treatment, including mortality and recovery, to improve health system planning. This cross-sectional descriptive study analyzed the costs and consequences of COVID-19 treatment in one of the largest referral training centers for patients in Lorestan province, Iran. The study examined hospital documents from the beginning of January to the end of December 2022. The results showed that the recovery rate of patients was approximately 87%, and the average cost per patient was 161 USD. More than 70% of this cost was related to medication and hospital bed expenses. Lopinavir was the most prescribed medication, and Immunoglobulin and Remdesivir had the highest cost share among all medication expenses. Given the significant proportion of medication and hospitalization expenses, it is recommended that the new approach to prescribing medications and managing patient care should be centered around standardized treatment protocols and home-based care. This is particularly crucial in developing countries with limited resources and clinical evidence. It is important to note that the calculation of standard treatment costs has limitations and should be interpreted cautiously.

Removing polyethylene oxide and polypropylene oxide co-polymer template to generate porosity is critical in synthesizing SBA 15 (MSN). Porosity generation among silica nanoparticles is in high demand due to its wide applications. Different physical treatments like calcination, solvent extraction ultrasonication, and a combination of methods were implemented to remove organic templates from pores. The particles obtained were characterized using FTIR to expose silanol functional groups. The PSL-5 particles were obtained via combination treatment, which was economical and was selected to formulate mosquito repellent cream. The optimized cream formulation with and without an MSN carrier was evaluated for mosquito repellency using diurnal mosquitoes and blank active citronellol using the arm cage method. The uniformity of particle size distribution and hexagonal porosity represented by crystallinity were evident from the SEM and XRD data. The zeta potential of -16.8 mv of SBA 15 indicates the stability of the particles. Comparison of FTIR of carrier SBA 15 and citronellol shows no incompatibility. The mesoporous material effectively deters mosquitoes for more than 3 hours. The novel template removal process utilizes mild temperature and a less solvent ratio of 1:3. Thus, the obtained MSN material showed prolonged mosquito repellency in the laboratory assay.

Over the years, medicinal plants have been considered promising treatments for managing various disorders. Numerous natural products contain prospective potential for the treatment of insomnia. This study aimed to determine the quantities of melatonin and GABA present in five plant extracts with hypnotic effects. Five plants were selected for investigation, including Valeriana officinalis, Passiflora incarnata, Aloysia citriodora, Withania somnifera, and Lavandula officinalis. The ethanolic extracts of these plants were prepared using the maceration method. For preliminary phytochemical evaluations, HPTLC fingerprinting was conducted on both the extracts and the standards, including melatonin and GABA. GABA content was determined using HPTLC in three out of the five plants. Furthermore, the HPLC method was used to confirm the presence of melatonin. The results of HPTLC fingerprinting revealed that the ethanolic extracts of Aloysia citriodora, Passiflora incarnata, and Withania somnifera contained GABA, which could be attributed to their reported hypnotic effects. Conversely, none of the five plants contained melatonin, indicating that the hypnotic effect was not related to this compound. In conclusion, this study described the HPTLC method for detecting and quantifying GABA in Withania somnifera and Aloysia citriodora for the first time. Notably, Withania somnifera exhibited the highest amount of GABA.

Acetaminophen can put the kidneys at risk of serious damage by affecting the renal antioxidant system and its cellular pathways. Achillea millefolium L. has been found to have antioxidant properties. This study aimed to determine the effect of Achillea millefolium L. (Ach) extract on acetaminophen-induced nephrotoxicity in rats. In this experimental research, 36 male Wistar rats were used. High-performance liquid chromatography (HPLC) analyzed Ach compounds. Animals were randomly assigned to six groups (n=6), which included vehicle, Ach 300 mg/kg, acetaminophen, acetaminophen + Ach (50, 150, and 300 mg/kg). Then, animals received acetaminophen (Single dose, 500 mg/kg), and after 1 hour, they received solutions containing saline/Ach as a single dose by oral gavage. After 24 hours, blood urea nitrogen (BUN) and serum creatinine were determined using the relevant kit. Also, the malondialdehyde (MDA) concentration and the activity of glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD) were measured by the spectrophotometric method. Also, hematoxylin and eosin staining methods obtained renal tissue damage scores (RTDS). The results revealed that acetaminophen significantly increased the serum creatinine, BUN, RTDS, and MDA concentration and decreased the catalase, GPx, and SOD enzymes activity levels in renal tissues of the acetaminophen-administered rats versus the control (P<0.05). Ach treatment could significantly ameliorate these changes in acetaminophen + Ach (300 mg/kg) compared to the acetaminophen group (P<0.05). The present study revealed that Ach may protect against renal injury induced by acute acetaminophen poisoning, at least through its antioxidant effect.

New medicines for Staphylococcus aureus strain resistance are being developed using an in silico approach, modifying monoglyceride with vanillic acid to balance hydrophilic and hydrophobic properties. Furthermore, the structure of the design compounds (M1-M9) was optimized using the AM1 method and docked to Staphylococcus aureus penicillin-binding protein 2a (SauPBP2a) (PDB ID: 1mwt) as a receptor. The binding energy and molecular interaction were evaluated and compared to Penicillin G as a standard. The best dock score of a designed compound is used to evaluate its complex stability using molecular dynamics simulation. The docking results revealed that the monoglyceride containing vanillic acid improved the interaction with the receptor. Increasing the number of methylene chains (-CH₂-) in the acyl group on the saturated product reduced binding energy. The outcomes also demonstrated that monorisinoleylvanillate (Compound M9), an unsaturated monoglycerylvanillate, exhibited the best binding energy of -7.1 kcal/mol. Ser462 and Asn464 are two important amino acids for catalytic domains that interact well with the product, having binding distances of 2.64 and 2.01, respectively. The M9 compound was the most stable SauPBP2a complex among design compounds, as confirmed by molecular dynamics simulation using CABS-Flex and the iMODS server. This compound will be synthesized using vanillic acid and methyl ricinoleate, and its activity against MRSA will be validated through in vitro assays in subsequent research.

Rabies is a fatal disease that may be transmitted from animals to humans. It is caused by a virus called rabies virus (RABV), which is a kind of RNA virus belonging to the family Rhabdoviridae and the genus Lyssavirus. Current rabies vaccines, while effective, require multiple doses for adequate protection, which presents significant financial and logistical challenges, especially in low-resource settings. Additionally, the risk of reversion to virulence in live-attenuated vaccines limits their use. This study aims to design and optimize the rabies virus glycoprotein (G protein) using in silico methods to address these challenges and develop a more effective and accessible rabies vaccine. The nucleotide sequences of the rabies virus glycoprotein were acquired from GenBank (accession number LT839616) and optimized to improve expression in Chinese Hamster Ovary (CHO) cells using bioinformatics tools. PSIPRED was employed for secondary structure prediction, and SWISS-MODEL was used for 3D structure modeling. The optimized gene was synthesized and inserted into the pcDNA3 vector. CHO cells were transfected with the recombinant plasmid, and the presence of the expressed gene was confirmed using RT-PCR and Western blot analysis. Optimizing the codons significantly enhanced the synthesis of the G protein derived from the rabies virus in CHO cells. Structural analyses confirmed the stability and proper conformation of the protein. The gene was successfully subcloned into the pcDNA3 vector, and its expression in CHO cells was verified using RT-PCR and Western blot analysis, demonstrating the effective production of the recombinant glycoprotein. This study successfully utilized bioinformatics and experimental methodologies to optimize the rabies virus G protein, demonstrating its potential as a viable vaccine candidate. The results provide a strong foundation for developing an advanced rabies vaccine that is both effective and accessible, particularly in regions where rabies remains prevalent.

Underreporting of adverse drug reactions (ADRs) due to time constraints, limited awareness, reluctance, and legal fears demands integrating pharmacists with physicians and implementing an extensive continuing education module on pharmacovigilance for application-based learning. Our study aimed to integrate a pharmacist with a treating physician to enhance patient safety by facilitating ADR reporting, providing a continuing education module on pharmacovigilance to senior residents and interns, and providing an ADR alert card to patients. We carried out a cross-sectional study over ten months in the general medicine department of a tertiary care hospital. We integrated Doctor of Pharmacy intern students with treating physicians to facilitate easy identification of ADR and for issuing ADR alert cards. We provided a seven-day continuing education module on pharmacovigilance concepts for senior residents and final-year medical interns. We distributed an ADR alert card to 180 patients. The largest groups of patients affected by ADRs in our study were aged between 41-50 and 51-60 years, collectively accounting for nearly 50% of the affected population. Our study reported a slight female predominance (51.1%). The gastrointestinal system (31.1%), nervous system (20%), and skin and subcutaneous tissue (13.9%) were the most frequently affected organ systems, accounting for 65% of the ADRs. Most ADRs (92.2%) were not serious. Analgesics (aspirin), HMG-CoA inhibitors (atorvastatin), and antiepileptics (phenytoin) were the top three drug classes most associated with ADRs. Out of 23 participants, 21 (91.3%) correctly completed the reporting of ADR into the ADR form from anonymous case reports, identified predisposing factors, assessed causality correctly, and suggested prevention and management strategies according to the clinical scenario. Most participants (95.7%) indicated that the module significantly enhanced their awareness and comprehension of Pharmacovigilance concepts, with only a small percentage (4.3%) expressing neutral sentiment and none disagreeing. Integrating pharmacists, continuing pharmacovigilance education, and issuing ADR alert cards significantly enhanced ADR reporting, comprehension of pharmacovigilance concepts, and patient safety measures in the healthcare setting.

Investigation of the in-vitro anti-cancer and apoptosis activity of various extracts of M. rubicaulis (Lam.) against cancer cell lines (HepG2 and L929) is important. The HepG2 and L929 Cell lines were exposed to increasing concentrations of various extracts of leaves of M. rubicaulis (Lam.) ranging from 640 to 20 µg/ml for 24 hours. MTT assay was used to determine cytotoxicity. All extracts of leaves of M. rubicaulis (Lam.) treated with cancer cell lines HepG2 and normal cell line L929 in response to increasing concentration, cell viability decreased significantly. Additionally, the most affected cells were HepG2 cells, followed by L929. The study found that when exposed to ethanolic extract, the cancer cell lines (HepG2) showed the highest expression, while the normal cell lines (L929) showed the lowest. Based on the experimental data, we discovered that M. rubicaulis (Lam.) has a cytotoxic effect on cancer cell lines. In contrast, no cytotoxic effect was observed at the highest dose on normal cells. The ethanolic extract had potent anti-cancer activities against HepG2 cells via induction of Apoptosis by Flow Cytometry. According to the findings ethanolic extract has a high cytotoxicity against HepG2 cells, with an IC₅₀ of 93.69 µg/ml. Apoptosis processes such as alterations in cell shape, chromatin condensation, membrane swelling, and the production of apoptotic bodies were seen in ethanolic extract treated HepG2 cells. The ethanolic extract treated HepG2 cells variations in light scattering reveal the general characteristics of cell death due to apoptosis. These outcomes show how effective ethanolic extract of M. rubicaulis (Lam.) to exert apoptosis, particularly in late stage apoptosis in HepG2 cell lines. Hence, further investigation is required to study the phytoconstituents in ethanolic extract of M. rubicaulis (Lam.) responsible for cytotoxic activity.

The antimicrobial activity of the methanol extract of Parietaria officinalis from Guilan Province in northern Iran was evaluated against Escherichia coli (E. coli) (Gram-negative) and Staphylococcus aureus (S. aureus) (Gram-positive) using the microtitre plate method to determine the Minimum Inhibitory Concentration (MIC). The Folin-Ciocalteu method was used to analyze the total phenolic compounds. The amount of flavonoids present was determined using the colorimetric aluminum chloride technique. The essential oil of P. officinalis was analyzed to identify its primary components through chemical analysis. Gas Chromatography with a flame ionization detector (GC-FID) and Mass Spectrometry (MS) using a gas chromatograph (GC) (GC-MS) were utilized to analyze the components of the essential oil from wild-grown P. officinalis in Iran. The lowest concentration that inhibits growth for Staphylococcus aureus is 0.01 mg/µL, while for Escherichia coli is 5 mg/µL. The extract showed greater effectiveness against S. aureus than the gram-negative bacteria, E. coli. The total phenolic content was measured at 72.06 (SD=1.48), equivalent to micrograms of phenolic compounds in terms of gallic acid per milligram of dry methanolic extract. The total flavonoid content was recorded at 48.14 (SD=5.05), equivalent to micrograms of flavonoid compounds per milligram of dry methanolic extract. Among 65 observed compounds, 62 components were identified, constituting approximately 98.2%. The oil was rich in geranyl acetate (15.0 %), Viridiflorol (8.9%), trans-β-Ionone (4.8%), Caryophyllene oxide (4.7%), Hexahydrofarnesyl acetone (4.2%), 2,3-Epoxygeranial (4.2%), Bornyl angelate (2.3%) and (-)-Spathulenol (2.2 %). This research found that P. officinalis could be a promising natural substitute for antibiotics in treating S. aureus infections. The antibacterial effects are likely due to its phytochemical components. Results indicated that the P. methanolic extract possessed significant potential for both flavonoid and phenolic content. The extract obtained by the proposed procedure is enriched with flavonoids and is a candidate for a wide range of pharmacological properties.

Motor neuron disease (MND) is a collection of degenerative neurological disorders that impact the motor neurons responsible for controlling involuntary muscular movements. Amyotrophic lateral sclerosis (ALS) is the predominant variant, affecting both the upper and lower motor neurons in the brain and spinal cord. As the disease progresses, these neurons deteriorate, leading to muscle weakness, wasting, and inability to regulate voluntary motions. ALS can impair speech, swallowing, and breathing, causing significant impairment over time. Additional types of motor neuron disease (MND) encompass primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), and progressive bulbar palsy (PBP). These types exhibit variations in the location and severity of motor neuron involvement, but they all share the progressive degeneration of motor neurons. Treatment may involve medication, physical therapy, assistive equipment, and supportive care to manage symptoms and consequences over time. This review's primary aim is crucial for gaining a deeper understanding of the disease's fundamental causes and creating innovative therapies or interventions to enhance the outlook and quality of life for individuals suffering from MND.

Author Package-2024-Vol.20-Issue4