Iraqi Journal of Pharmaceutical Sciences
Iraqi Journal of Pharmaceutical Sciences (IJPS) is the official journal of the College of Pharmacy, University of Baghdad. The IJPS is a biannual specialized scientific journal which was first founded in 1979. The aim of this journal is to support scientific knowledge and encourage scientific research and publications. The IJPS provides a forum for reporting innovations, production methods, technologies, initiatives and the application of scientific knowledge to all aspects of pharmaceutical sciences, including advanced drug delivery systems, drug targeting, pharmacodynamics, pharmacokinetics, pharmacogenomics, biopharmaceutics, drug and prodrug design, pharmaceutical analysis, drug stability, quality control, pharmaceutical engineering, and pharmacy practice . The journal has issued thirty volumes and fifty three issues from 1979 until December of 2021. Iraqi Journal of Pharmaceutical Sciences (IJPS) is an open access peer-reviewed journal. Open access (OA) refers to a free and unrestricted online access to journal articles. The OA content is open to all with no access fees. For more information on Creative Commons license and the benefits of publishing an open access article
University of Baghdad- College of Pharmacy
Designing Stable Amorphous Solid Dispersions: Insights into Polymer Selection Strategies
Poor aqueous solubility remains a limiting step for many recently discovered active pharmaceutical ingredients (API), especially the drugs that are classified under the Biopharmaceutics Classification System (BCS) Class II and IV. These compounds exhibit poor dissolution in gastrointestinal fluids which leads to limited oral bioavailability. One of the strategies that has been studied to combat this challenge is Amorphous solid dispersion (ASD), which acts by improving the drug solubility through molecular dispersion in polymeric carriers. However, the efficacy of ASDs is significantly dependent on the ability of the recruited polymer to maintain the drug in an amorphous state and ensure physical and chemical stability for a long term. Therefore, there is a great interest in rational methods to guide this selection. In this review, the critical criteria involved in polymer screening, including drug-polymer interaction, miscibility along with glass transition temperature (Tg), and hygroscopicity, are discussed. Experimental and analytical techniques ranging from film casting and precipitation inhibition to Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRPD), Fourier Transform infrared (FTIR), and Nuclear Magnetic Resonance (NMR). Gordon–Taylor (G-T) equation, and Flory-Huggins (F-H) theory, among other methods, are also discussed as part of theoretical approaches. Furthermore, the review examines advanced computational tools such as molecular dynamics simulations (MDs) and machine learning (ML) models, which provide new opportunities for predictive formulation design, in addition to some of their strengths and limitations.
amorphous solid dispersion, polymer selection, solubility enhancement, physical stability, miscibility prediction.
amorphous solid dispersion, polymer selection, solubility enhancement, physical stability, miscibility predictio
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Protective Effect of Chromium Picolinate on Methotrexate Induced Nephrotoxicity in a Rat Model
Methotrexate, a folic acid antagonist, is a chemotherapeutic agent frequently employed in treating certain forms of cancer. Nephrotoxicity caused by high-dose Methotrexate is a medical emergency due to the delayed renal excretion of Methotrexate. Chromium is a trace element found in certain foods and the environment. The primary function of chromium is to regulate glucose levels, which is used as a supplement by people with type 2 diabetes Mellitus. This study aimed to evaluate the renoprotective effect of chromium against Methotrexate-induced Nephrotoxicity in rats. Thirty-two Wistar rats were allocated into four groups and treated as Group-1 (Control group): The rat was administered distilled water orally as a vehicle for eight consecutive days. Group-2 (Induction group): Methotrexate was injected in rats at a single dose of 20 mg/kg intraperitoneally on the first day. On the following day, the rats received distilled water for seven days. Group-3 (Chromium 2mg): methotrexate injected Rats at a dose of 20 mg/kg intraperitoneally, as a single dose on the first day. On the following day, the rats received Chromium picolinate at a dose (2mg/kg) orally by oral gavage for seven days. Group-4 (Chromium 4mg): Methotrexate injected in rats at a dose of 20 mg/kg intraperitoneally, as a single dose on the first day. On the following day, the rats receive Chromium picolinate at a dose (4mg/kg) orally by oral gavage for seven days. The Results of our study indicated that injection (20mg/kg) of Methotrexate caused a significant increase in creatinine and blood urea nitrogen, malondialdehyde, and a significant reduction in superoxide dismutase-1. Interestingly, treatment with chromium picolinate (2mg/kg) and (4mg/kg) showed significant drops in creatinine and blood urea nitrogen and malondialdehyde and a significant elevation in superoxide dismutase-1 compared to Methotrexate-treated rats. In conclusion, the current investigation revealed that the administration of chromium to rats has a beneficial impact on reducing Nephrotoxicity generated by Methotrexate. This is achievd by enhancing antioxidant defenses of the kidneys.
antioxidants, Nephrotoxicity, Chromium picolinate, Methotrexate, Superoxide dismutase.
Comparison Study of Montelukast with Dexamethasone for Possible Protection against Lipopolysaccharide-Induced Oxidative Damage in Bone Marrow of Albino Male Mice
Oxidative stress arises when the host defensive mechanisms of anti-oxidants cannot withstand the fierce attack launched by numerous reactive oxygen and nitrogen species. This prooxidant-antioxidant imbalance can cause endocrine, cardiovascular, pulmonary, and neurological disorders. In sepsis, this imbalance promotes organ failure, including bone marrow. The aim is to evaluate the anti-oxidant effect of montelukast compared with dexamethasone against LPS-induced oxidative stress in bone marrow. For this purpose, twenty-eight male Albino mice were randomly assigned to four groups of seven per each. Group I (control) received distilled water by oral gavage once a day for a week and euthanised on the 8th day; Group II (induction) received a single intraperitoneal injection of LPS 10 mg/kg and euthanised on the 2nd day. Group III received oral gavage dexamethasone 2.5 mg/kg once a day for a week, then two hours after the final dose, LPS was given and euthanised on the 8th day. Group IV received oral gavage montelukast 20 mg/kg once a day for a week, then two hours after the final dose, LPS was given and euthanised on the 8th day. Results showed that the LPS-model group had significantly higher malondialdehyde and myeloperoxidase levels than the control group. Pretreatment with dexamethasone (group III) and montelukast (group IV) significantly lowers both values. In bone marrow histopathology, montelukast reduced inflammatory cells without affecting red blood cells. In conclusion, Montelukast may be a promising anti-oxidant and a medication to prevent terrible oxidative stress results in humans.
dexamethasone; oxidative stress; montelukast
Rizatriptan Benzoate Mucoadhesive Nasal Delivery for Targeting the Brain Pharmacokinetics of Nasal Delivery and Intravenous Solution in Wistar Rats
Owing to the restricted oral bioavailability of antimigraine drugs Rizatriptan Benzoate (RNB), nasal delivery was employed in lieu of enhancing the bioavailability and brain targeting through utilizing spanlastics nanovascular. This work sought to formulate RNB as mucoadhesive spanlastics nanovesicles and assess the pharmacokinetic parameters and histopathological effects of the formulations on the nasal mucosa of rats. RNB was formulated as mucoadhesive spanlastics nanovesicles; the study comprised 68 Wistar rats, each weighing 200±35 g, divided into three groups (control, IN, and IV). RNB is quantified in rat plasma and brain using reverse-phase high-performance liquid chromatography (RP-HPLC). The pharmacokinetic studies on rats indicated that the brain Cmax of intranasal mucoadhesive RNB spanlastics was approximately two times greater than that of intravenous RNB – solution. No damage to the structure of the mucosal membrane was seen during the histological analysis. Consequently, the developed and optimized intranasal mucoadhesive RNB formula demonstrated outstanding potential for safe and effective administration of RNB. Keywords: Rizatriptan benzoate. Mucoadhesive spanlastics, Nasal delivery ,Brain targeting
Rats ,Rizatriptan Benzoate, Soluplus®, Span® 60, Spanlastics .
Tizanidine Cubosomal Nano Carriers as Transdermal Delivery System: Preparation and Characterization
Cubosomes are lipid-based nanostructured aqueous dispersions that form through a highly organized spontaneous self-assembly process. these lipid-based dosage forms can serve as effective carriers for lipophilic, hydrophilic drugs, thereby improving the therapeutic effectiveness of the drugs., cubosomes were developed in order to investigate their efficacy as nano carriers for transdermal delivery of tizanidine (TZN), a skeletal muscle relaxant with low oral bioavailability , cubosomal vesicles were formulated using the thin-film hydration technique, employing glyceryl monooleate (GMO) as the lipid component and poloxamer 407(p407) as the stabilizer. the vesicle characteristics were modified by varying the surfactant-to-lipid ratio. the prepared formulations were evaluated for vesicle size (VS), polydispersity index (PDI), and entrapment efficiency (%EE). the optimized formulation was further subjected to an in vitro release study, zeta potential measurement, field emission scanning electron microscopy (FESEM), and compatibility analysis using Fourier-transform infrared (FTIR) spectroscopy. additionally, differential scanning calorimetry (DSC) were conducted to compare the optimized formulation with the pure drug. the results demonstrated significant variations in certain physicochemical properties like particle size and EE. the optimized formulation, designated as F9, exhibited a vesicle size of 160.7 ± 4.785 nm, a PDI of 0.061 ± 0.048, an entrapment efficiency of 76.8 ± 0.17%, and a zeta potential of -23.46 ± 4.088mV, respectively, in vitro drug release study demonstrated controlled and sustain release profile from cubosomal dispersion photo micrographic analysis of the cubosomal dispersion confirmed a uniform cubic morphology with good dispersion stability. these findings suggest that the thin-film hydration technique is an effective approach for developing stable cubosomal dispersions
Novel Variants in the MDR1 Gene with the Potential to Discriminate Steroid Responsiveness in Iraqi Children with Idiopathic Nephrotic Syndrome
Steroid-resistant idiopathic nephrotic syndrome (SRNS) is a leading cause of childhood end-stage renal disease, with diverse histological features and a challenging diagnosis. SRNS has been suggested to develop due to variations in the multidrug resistance 1 (MDR1) gene, with variable results from different studies. This study explored the presence of novel variants in the MDR1 gene and evaluated their association with steroid responsiveness in Iraqi children with idiopathic nephrotic syndrome. This case-control study included children with SRNS (n=30) and steroid-sensitive nephrotic syndrome (SSNS; n=30) from the pediatric nephrology clinic in Babylon Hospital for Maternity and Pediatrics. Genomic DNA (gDNA) was extracted for each participant from a venous blood sample using the chemical salting-out method. The soluble gDNA was separated later on using a silica column under high salt conditions. Specifically designed primers were utilized in a polymerase chain reaction to produce the MDR1 gene amplicons. The participants were genotyped by utilizing Sanger sequencing. This study detected three novel variants: g.87531179A>T (NV1), g.87531184T>A (NV2), and g.186784C>T (NV3). A higher risk of SRNS development was significantly associated with the NV1 A/T genotype [odds ratio (OR) and 95% confidence interval (95% CI): 3.29 (1.09–9.95), p=0.035] and the NV2 A/A genotype [OR (95% CI): 14.73 (1.64–132.64), p=0.016] compared to the wild genotype. In contrast, the NV3 C/T genotype was associated with a lower SRNS risk [OR (95% CI): 0.064 (0.016–0.26), p < 0.001] compared to the wild genotype. Moreover, the haplotype analysis showed that the likelihood of developing SRNS was significantly lower among the carriers of the ATT haplotype [OR (95% CI): 0.24 (0.1–0.56), p < 0.001], which represents the wild alleles of the NV1 and NV2 variants and the mutant allele of the NV3 variant. The findings concluded that children with the NV3 wild genotype alone or in combination with the NV1 mutant heterozygous and NV2 mutant homozygous genotypes were more likely to develop SRNS, and an alternative immunosuppressive plan might be necessary. Additional research is needed to decipher the steroid pharmacogenetics, which would reveal further insight that is vital to individualizing medication treatment in nephrotic children.
Exploring the In vivo Antiangiogenic Activity via CAM Assay and In vitro Cytotoxic Effects of Iraqi cultivated Leonotis leonurus Methanol Leaf Extract Against A2780 Human Ovarian Cancer Cells
The in vivo antiangiogenic activity and in vitro cytotoxic effects of methanol leaf extract of Leonotis leonurus (Lamiaceae) against A2780 human ovarian cancer cells are investigated in this work. Leonotis leonurus (L. leonurus), a fellow of the Lamiaceae family and commonly Referred to as "wild dagga," or “lion’s ear” is a commercially important plant The antiangiogenic capacity was evaluated with the Avian chorioallantoic membrane (CAM) assay to reveal 100% inhibition of blood vessel growth at 500 mg/mL. Cytotoxicity was measured using the MTT assay; a dose-dependent drop in cell viability resulted from an IC50 value of 93.22 µg/mL. Phytochemical analysis investigation detects the presence of significant amounts of phenolic acids (chlorogenic acid: 342.7 ppm; caffeic acid: 106.11 ppm) and flavonoids (resveratrol: 665.4 ppm; apigenin: 280.2 ppm) using reversed-phase HPLC with novel isolation of resveratrol from the plant for the first time. The presence of these phytochemical is linked to angiogenesis suppression and death induction. Statistical analysis (Tuk's test) with p < 0.05 confirmed notable cytotoxic effects at all dosages. These findings highlight L. leonurus as a possible natural source of bioactive compounds with cytotoxic and antiangiogenic properties, hence worthy of future investigation for the creation of anticancer treatments.
Leonotis leonurus; antiangiogenic activity; cytotoxicity; CAM assay; ovarian cance.r; phenolic compounds; resveratrol; chlorogenic acid.
antiangiogenic activity; cytotoxic effect; CAM assay; leonotis leonurus; A2780 ovarian cancer cell; phytochemical screening; natural product research.
Assessment of Adherence, Quality of Life, and Self-efficacy Among Iraqi Patients with Systemic Lupus Erythematosus: A Single-center Study
Systemic Lupus Erythematosus (SLE) is an immune-mediated disease with severe morbidity and tissue damage. Adherence to therapy in SLE patients remains a significant problem, and nonadherence can lead to poor disease outcomes and decreased quality of life. Self-efficacy is also a critical aspect of disease control and medication adherence. This study aims to evaluate medication adherence, quality of life, and self-efficacy among patients with SLE and their correlation with sociodemographic and clinical factors. This was cross-sectional study was conducted at Baghdad Teaching Hospital's Rheumatology Unit from November 2024 to January 2025, evaluating adherence, quality of life, and self-efficacy among SLE patients using the Compliance Questionnaire for Rheumatology (CQR), the World Health Organisation Quality of Life Questionnaire (WHOQOL-BREF), and Self-Efficacy for Managing Chronic Disease 6-Item Scale (SEMCD) respectively. In addition, the SLEDAI was used to measure the disease activity. The study recruited 118 individuals aged 35.03±10.52 years old on average, and 94.1% did not receive the flu vaccine in the past year. The average CQR score was 64.32, and 12.7% of the patients adhered to the therapy; the WHOQOL-BREF psychological score was at its minimum value of 9.90, while the social score attained the maximum value of 12.21, and the average SEMCD score for the subjects was 39.88. The adherence score significantly correlated with residency and SELENA-SLEDAI. In addition, WHOQOL-BREF scores demonstrated a significant correlation with residency, exercise, SELENA-SLEDAI, disease duration, and the number of chronic diseases. The SES6C score is also associated with residency, SELENA-SLEDAI, and the number of chronic drugs. The study identified a significant positive correlation among self-efficacy scores, medication adherence scores, and four aspects of quality of life. The study concluded that patients with SLE demonstrated low flu vaccine uptake, suboptimal medication adherence, relatively low quality of life regarding the psychological domain score, and relatively high self-efficacy in managing chronic disease. Finally, the study revealed the need for effective communication between healthcare providers and patients regarding infection risks and benefits of flu vaccine. Furthermore, augmenting patient education to enhance medication adherence and improve self-efficacy in managing chronic disease can positively impact treatment outcomes and, hence, patient quality of life.
SLE, Iraqi patients, adherence, quality of life, self-efficacy, flu vaccine
SLE, Iraqi patients, adherence, quality of life, self-efficacy, flu vaccine.
Stevia-Derived Diterpenoids as Potential Dopamine D2 Receptor Antagonists for Insomnia and Schizophrenia Therapy: An In Silico Study
Insomnia is the second most common mental disorder and causes several health risks. Stevia water extract is a popular natural sweetener and promotes health benefits including antioxidant, anti-inflammatory, antimicrobial, antidiabetic, anticancer, anti-hypertension. This study investigates the potential of Diterpenoid-Water-Extract Compounds as a target for insomnia therapy through the use of dopamine receptors (D2/D4) in silico. This research method includes: Stevia water extract compounds resulting from LCMS analysis as ligands and proteins of D4 dopamine receptor (id: 5wiv) and D2 dopamine receptor (id: 6cm4) were taken from the database, then native ligands and bioactive compounds were docked again and their interactions were analyzed. The best binding affinity results are based on the stability of the interaction using molecular dynamics simulations. The docking results showed that several water stevia extract compounds bound to the same dopamine D2 and D4 receptor sites as the original ligand. Binding affinity shows relatively similar scores for both water and original stevia extract compounds against the D2-Dopamine dopamine receptor. This results, molecular docking analysis of water stevia extract compounds shows that the active site interactions and binding affinity are the best for selective D2-Dopamine receptors, including Steviolmonoside, Steviolbioside, Sterebin-G, -E, -B, -M, -A, and -K , Steviol, and Isosteviol. These diterpenoid compounds also have stable interactions with D2-dopamine in dynamic molecular simulations. The conclusion of this research is the diterpenoids compounds in water stevia extracts, such as Steviolbioside, Steviolmonoside, Rebaudioside G, Sterebin G, Sterebin M, Steviol, and Isosteviol have the ability to target insomnia therapy through D2-Dopamine receptor inhibition/antagonist
Assessing the Clinical Significance of Monocyte Chemoattractant Protein 1 and Protein Oxidation Products in Patients with Chronic Periodontitis
An essential chemokine called monocyte chemoattractant protein-1 (MCP-1) is in charge of initiating, controlling, and mobilizing monocytes to the sites of active severe periodontal inflammation. The purpose of the current study is to assess the serum levels of MCP-1 and protein oxidation products in chronic periodontitis patients, namely Advanced Oxidation Protein Products (AOPP), 3-Nitrotyrosine (3-NT), and Protein Carbonyl (PC). Evaluation of potential relationships between MCP-1 levels and the byproducts of protein oxidation. In the current investigation, 45 patients with severe chronic periodontitis (diseased) and 14 healthy individuals took part. Enzyme-linked immunosorbent assay was used to measure the amounts of MCP-1, AOPP, 3-NT, and PC in samples obtained from each participant. Using R statistical software, tests of correlation and linear regression were carried out. Serum levels of MCP-1, AOPP, 3-NT, and PC were considerably greater in the periodontitis group than in the control group among those with periodontitis. Protein oxidation metrics and MCP-1 exhibited a positive connection. It is indicated that elevated levels of MCP-1, AOPP, 3-NT, and PC could be a possible biomarker for periodontal disorders and that these levels may play a significant role during periodontal inflammation.
Monocyte chemoattractant protein‐1, Nitrotyrosine, Oxidative stress, Periodontitis, Protein carbonyl
Identifying Medication-Related Risk Factors among Iraqi Hospitalized Older Patients with Cardiovascular Disease: A Cross-Sectional Study
Cardiovascular drugs are the most commonly prescribed therapeutic classes among older adults, reflecting the high burden of cardiovascular diseases in those patients. Prescribing in elderly people is challenging due to age-related physiological changes, geriatric syndromes, and multi-morbidity. Identifying risk factors associated with medication use is imperative to improve medication management, reduce the risk of medication errors, and optimize therapeutic outcomes. The aim of the present study was to explore medication-related risk factors among a group of older patients. A cross-sectional study was conducted using convenience sampling method to enroll hospitalized older patients attending the Cardiac Care Unit of Baquba Teaching Hospital in Diyala province from December 2024 to February 2025. Risk factors were estimated through the validated Medication Risk Questionnaire (MRQ). A total of 200 patients were included in the study, of whom 111(55.5%) were female. The median age (interquartile range) was 71 (68-74) years. Using more than five medications (89.5%), having more than one physician involved in their healthcare (39.5%), using medications for three or more different health conditions (63.5%), using narrow therapeutic index medications (36.5%), and frequent changes to their medication regimen (35%) were among the types of detected risk factors. Based on MRQ, various factors that may place older patients at risk for drug-related problems had been identified. These findings underscore the need for multi-faceted interventions like periodic structured medication review, medication reconciliation, and applying de-prescribing practices to avoid problematic polypharmacy, ensure the rational use of medications, and reduce unnecessary healthcare utilization.
Cardiovascular disease, Medication-related problem, Older adults, Polypharmacy, Risk assessment
Risk factors for drug-related problems among older adult patients
Formulation and Evaluation of Ion-Responsive in Situ Gel for Ocular Delivery of Lornoxicam: In Vitro and In Vivo Studies
Lornoxicam (LOX) is a potent nonsteroidal anti-inflammatory drug (NSAID) oxicam class; that can be used into treat ocular inflammation; when applied locally to the eye, reducing systemic side effects. However, a major challenge is its rapid lacrimal clearance. An ion-sensitive in-situ gel for lornoxicam (LOX) was developed using gellan gum, a polymer that gel in response to calcium ions present in physiological fluids. This method allows for the local and continuous release of medication, improving therapeutic efficacy. The aim of this study was to formulate and evaluate the efficacy of lornoxicam-loaded in-situ ocular gels Methods A surface solid dispersion of lornoxicam and Crospovidone was prepared and incorporated into the gellan gum-based in-situ gel. Different concentrations of gellan gum were tested changed to create various of formulations, and their impact on viscosity and gelation capacity was assessed. Results: In vitro release experiments; showed that the optimized formulation (F8), containing 0.1% (w/v) lornoxicam and 1% (w/v) gellan gum, released 91.7% of the medication within the first 30 minutes and continued to release over six hours. In an animal model using Rattus norvegicus Domestica, the formulation demonstrated significant therapeutic efficacy in reducing ocular irritation within 72 hours in vivo. Conclusion: The lornoxicam ocular in-situ gel appears to be a promising dosage form that enhances medication retention, reduces drainage, and provides therapeutic benefi
Lornoxicam, Crospovidone, Ion, Ocular In-situ gel, Gullan gum
Comparative Hepatoprotective Effects of Dapagliflozin and Silymarin Against Cyclophosphamide-Induced Liver Injury in Rats: Involvement of Nrf2/HO-1, HNF4α, and HNF6 Pathways
<a href="Background: Cyclophosphamide (Cpd), a common immunosuppressive and chemotherapeutic drug, can cause hepatotoxicity by inducing inflammation and oxidative stress. Dapagliflozin (Dapa) and other sodium-glucose cotransporter-2 inhibitors (SGLT2i) have anti-inflammatory and antioxidant properties, and Silymarin is a natural compound extracted from the seeds of the milk thistle plant (Silybum marianum). It is best known for its antioxidant, anti-inflammatory, and hepatoprotective effects.Objective: By measuring oxidative stress, inflammation, and liver regeneration parameters, with an emphasis on the Nrf2/HO-1 pathway and hepatocyte nuclear factors (HNF4α and HNF6), Dapa's hepatoprotective effects in comparison to Sil on Cpd-induced liver injury will be evaluated. Methods: Five (5) groups of male rats ten rats each were created: control, vehicle (Na-CMC), Cpd (30mg/kg), Cpd + Dapa (3mg/kg), and Cpd + Sil (200mg/kg).. Rat liver tissue was examined for Nrf2, HO-1 (qRT-PCR), HNF4α (ELISA), and HNF6 (Western blot) levels after ten days. Results: Cpd significantly reduced Nrf2, HO-1, HNF4α, and HNF6 levels (*p < 0.0001). Dapa and Sil restored these markers, with Dapa showing superior upregulation of Nrf2 (2.182 ± 0.540 vs. Cpd 0.244 ± 0.096) and HO-1 (2.051 ± 0.533 vs. CP 0.487 ± 0.178) (*p< 0.0001). Dapa also significantly increased HNF4α (2135 ± 297.9 vs. CP 229.5 ± 50.21) and HNF6 (3.635 ± 0.610 vs. CP 0.515 ± 0.255) (*p< 0.001), outperforming Sil in enhancing HNF6 (*p < 0.05). Conclusion: Dapa ameliorates Cpd-induced hepatotoxicity by activating the Nrf2/HO-1 pathway and restoring HNF4α/HNF6 expression, demonstrating comparable or superior efficacy to Sil. These findings highlight Dapa’s potential as an adjunct therapy to mitigate chemotherapy-induced hepatotoxicity">Background: Cyclophosphamide (Cpd), a common immunosuppressive and chemotherapeutic drug, can cause hepatotoxicity by inducing inflammation and oxidative stress. Dapagliflozin (Dapa) and other sodium-glucose cotransporter-2 inhibitors (SGLT2i) have anti-inflammatory and antioxidant properties, and Silymarin is a natural compound extracted from the seeds of the milk thistle plant (Silybum marianum). It is best known for its antioxidant, anti-inflammatory, and hepatoprotective effects.Objective: By measuring oxidative stress, inflammation, and liver regeneration parameters, with an emphasis on the Nrf2/HO-1 pathway and hepatocyte nuclear factors (HNF4α and HNF6), Dapa's hepatoprotective effects in comparison to Sil on Cpd-induced liver injury will be evaluated. Methods: Five (5) groups of male rats ten rats each were created: control, vehicle (Na-CMC), Cpd (30mg/kg), Cpd + Dapa (3mg/kg), and Cpd + Sil (200mg/kg).. Rat liver tissue was examined for Nrf2, HO-1 (qRT-PCR), HNF4α (ELISA), and HNF6 (Western blot) levels after ten days. Results: Cpd significantly reduced Nrf2, HO-1, HNF4α, and HNF6 levels (*p < 0.0001). Dapa and Sil restored these markers, with Dapa showing superior upregulation of Nrf2 (2.182 ± 0.540 vs. Cpd 0.244 ± 0.096) and HO-1 (2.051 ± 0.533 vs. CP 0.487 ± 0.178) (*p< 0.0001). Dapa also significantly increased HNF4α (2135 ± 297.9 vs. CP 229.5 ± 50.21) and HNF6 (3.635 ± 0.610 vs. CP 0.515 ± 0.255) (*p< 0.001), outperforming Sil in enhancing HNF6 (*p < 0.05). Conclusion: Dapa ameliorates Cpd-induced hepatotoxicity by activating the Nrf2/HO-1 pathway and restoring HNF4α/HNF6 expression, demonstrating comparable or superior efficacy to Sil. These findings highlight Dapa’s potential as an adjunct therapy to mitigate chemotherapy-induced hepatotoxicity
Extraction, Identification and Quantification of Vitexin and p-Coumaric Acid from Basella alba L. Cultivated in Iraq
The objective of this work is to isolate, characterize, and quantify two bioactive substances from Basella alba (Malabar spinach), a plant of nutritional and therapeutic value. Vitexin and p-coumaric acid were isolated and quantified using high-performance liquid chromatography (HPLC), and Their characterization was carried out using Fourier transform infrared spectroscopy (FT-IR), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the spiking method, where the isolated compound was compared with the standard for confirmation. confirmationThe concentrations of p-coumaric acid and vitexin in Basella alba were found to be 144 µg/g and 220 µg/g, respectively, which are higher than those identified in previous studies. This suggests that environmental factors, particularly light exposure and geographical conditions, may play a significant role in enhancing the production of these secondary metabolites. Soxhlet extraction was employed to isolate and quantify the compounds, demonstrating high recovery rates consistent with previous findings.. These results highlight the potential of Basella alba as a valuable plant for further research into its health benefits. Future studies should explore its applications in nutraceuticals and pharmaceuticals.
Evaluation of Androgen Receptor Expression and Its Association with Clinicopathological Features in Iraqi Women with Breast Cancer
Breast cancer is the most prevalent malignancy among women worldwide. Regarding the androgen receptor's existence as a likely prognostic indicator, there has been interest in its relationship with various molecular markers such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu), as well as its association with clinicopathological features and therapeutic targets. The purpose of this study was to investigate the expression of AR and its association with clinicopathological features in Iraqi women who were newly diagnosed with breast cancer. We retrospectively analyzed AR expression using immunohistochemistry from 96 tissue samples of breast cancer patients between February 2024 and January 2025. The association of AR with clinicopathological parameters, including age, tumor size, lymph node involvement, distant metastases, TNM stage, histological grade, molecular subtype, ER status, PR status, and HER2 status, was assessed. Tumors with at least 10% nuclear-stained cells were classified as positive for AR. The association between AR expression and other factors was determined using a chi-square test in SPSS. Approximately 63 (65.6%) of the 96 individuals were AR-positive. No significant association was found between AR expression and clinicopathological factors (P >0.05). In conclusion, while AR is expressed in 65.6% of breast cancer patients, there is no significant association with conventional clinicopathological characteristics. This indicates that AR has limited prognostic value in this population. However, its high expression necessitates additional research into its biological significance and potential as a therapeutic target in some breast cancer subtypes.
Androgen receptor, Breast cancer, Iraqi women
Evaluation of androgen receptor in breast cancer, Iraqi women, Immunohistochemistry, clinicopathological features.
Cytotoxic, Docking, and Pharmacokinetic Evaluation of Ethyl Acetate Fraction of Sungkai (Peronema canescens Jack) Leaves Against A549 Lung Cancer Cells
Sungkai (Peronema canescens Jack) is known to have various bioactive compounds as anticancer agents. This study aims to evaluate the anticancer potential of the active compound from the ethyl acetate fraction of sungkai leaves through an experimental and computational approach. The cytotoxic activity of the ethyl acetate fraction was carried out using the MTT assay method on A549 lung cancer cells. The computational study carried out using the molecular docking method and continued with pharmacokinetic analysis of the five main compounds in the ethyl acetate fraction of sungkai leaves. The MTT assay revealed that the ethyl acetate fraction exhibited moderate cytotoxic activity against A549 lung cancer cells, with an IC50 value of 33.41 µg/mL. The LC-MS/MS analysis identified five main compounds in this fraction: isorhamnetin, physcion, pilosin, (3R)-sophorol, and takakin. Molecular docking simulations of these compounds with the EGFR protein (PDB ID: 5UG9) showed bond energies ranging from -7.7 to -8.9 kcal/mol. Physcion has a more negative bond energy value compared to the positive control (quercetin) and four other compounds. The compounds interacted with the protein through hydrogen bonds and van der Waals interactions, predominantly involving amino acid residues ALA A:743, VAL A:726, LEU A:718, LEU A:844, and GLN A:791. Pharmacokinetic analysis revealed that all the compounds met Lipinski's rule of five, indicating good oral absorption and membrane permeation. However, toxicity predictions showed that isorhamnetin, takakin, and pilosin had a high risk of gene mutations, whereas physcion had a moderate risk. Despite potential toxicity concerns, the compounds had drug scores greater than 0, suggesting their potential as drug candidates. Therefore, experimental and computational approaches can be an efficient early screening method to identify potential bioactive compounds as drugs. However, further analysis must be carried out regarding the risk of toxicity and a good dose of the drug.
Peronema canescens Jack, lung cancer, molecular docking, cytotoxicity, pharmacokinetics
Possible Hepatoprotective Effect of Two Different Doses of Acai Berry Extract Alone and in Combination with Orlistat on High-Carbohydrate, High-Fat Diet-Induced Obesity in Male Rats
Obesity is complex and chronic disease . it had negative impact on general health , quality of life and elevation in mortality rate . The liver is the most affected organs by obesity. The use of plants different active constituents which had different pharmacological effects. One of these constituents are the polyphenols which had antioxidants and anti-inflammatory effects. Accordingly, polyphenols nowadays have become one of the most important therapeutic protocols today. Acai berry extract's had different pharmacological benefits due to its anti-inflammatory and antioxidant activity The aim of the present study is to assess the hepatoprotective impact of acai berry extract in rats fed a diet rich in fat and carbohydrates. To achieve this aim, 48 albino rats were divided into Group I. rats receive normal diets, group II: rats on high fats and carbohydrate diets, groups III , IV: rats on high carbohydrate and fat diets with Acai berry extract ( 250, 500mg/kg per day) respectively, groups V, VI; rats feed with high carbohydrate and fat diets with 10 mg/kg/day of orlistat and ( 250, 500mg/kg per day) respectively of acai berry extract. All the groups received their treatments for 12 weeks. At the end of study, serum was collected, and liver tissue were obtained to determine anti-oxidative, inflammatory, and liver function. In the present study, it have been found that, there was a significant elevation in the level of (superoxide dismutase, glutathione peroxidase) in tissue homogenate (p <0.05) and a significant reduction in the levels of liver function enzymes and (malondialdehyde, tumor necrosis factor alpha, tumour growth factors,interleukin-B1)( p < 0.05) when compared between groups III ,IV and the induction group. The present study showed that the extract of acai berries had hepatoprotective effects
AI-Based Approach To Screen Opioid Receptor Ligands Via Grind Fingerprints and Convolutional Neural Network
Opioid receptors belong to G-Protein Coupled Receptor (GPCR) family, and are divided into 3 subtypes of Mu, Kappa and Delta. The receptors are targeted by agonists and antagonists to manage variety of medical issues. Although main endogenous ligands for opioid receptors are peptides, a diverse set of non-peptide molecules can also bind orthosteric and allosteric sites of the receptor. Virtual screening for active agonists and antagonists using structure-based molecular docking is challenged by receptor flexibility, multimerization and orthosteric/allosteric sites coordination. Meanwhile, ligand-based virtual screening is more reliable. In this research grid-based alignment-independent molecular fingerprint (GRIND) and convolutional neural network (CNN) models are used to classify database of potential opioid ligands of experimentally measured activities. Six GRIND-CNN models were trained to recognize features within the fingerprint that are relevant to agonistic and antagonistic activities against each of Mu, Kappa and Delta receptors. The models performance measured by Area Under the Curve of Receiver Operating Characteristic (AUC-ROC), Matthews Correlation Coefficient (MCC) and Balanced Accuracy (BA). The GRIND-CNN models show mean AUC-ROC values (from 0.70 to 0.83) which are comparable to PubChem and Extended-connectivity fingerprints used for deep neural network (DNN) models (PubChem-DNN and ECFP-DNN, respectively. However, both of GRIND-CNN and PubChem-DNN models outperform ECFP-DNN model in recognition of activity-relevant features within relevant fingerprint (mean MCC values for Y-randomized training across all ligands groups are 0.05, 0.03 and 0.16, respectively). By using combined predictions of both GRIND-CNN and PubChem-DNN models with 0.5 coefficient for each, the mean AUC-ROC is improved (0.77 to 0.91) and MCC for Y-randomized training is reduced to 0.02, which indicates improved feature recognition. Saliency maps of GRIND fingerprints for models trained to differentiate agonists vs antagonists, and differentiate ligands vs non-ligands for different opioid receptor subtypes showed statically significant differences at correlogram bins (pixels) level. Such differences are related to message-address theory of opioid ligands. The research provides tools for virtual screening of opioid ligands that follow activity-relevant features recognition irrespective to molecular scaffold or size, in a manner similar to how a hand senses through distinct fingers the geometry of an object. The models are freely available on https://github.com/mohammednooraldeen/GRIND-CNN.
Alignment-independent finger print GRIND