REVIEW_ARTICLE Background: Nanostructured lipid carriers (NLCs) are advanced colloidal drug delivery systems composed of a mixture of solid and liquid lipids. Compared to metallic or polymeric nanoparticles, NLCs are considered safer, non-toxic, and biocompatible, making them highly suitable for pharmaceutical applications. Objectives: This study aimed to provide an in-depth overview of NLCs, focusing on their composition, structural characteristics, methods of preparation, advantages, and recent advancements, particularly in the formulation of lipid nanocarrier-based gels. Methods: NLCs are formulated using various techniques, such as high-pressure homogenization, solvent evaporation, and microemulsion methods. These approaches, along with the use of appropriate solid and liquid lipids and surfactants, enable the customization of NLCs for specific therapeutic needs. The study reviewed recent literature to assess the performance and potential of NLCs in drug delivery. Results: NLCs exhibit improved stability, enhanced drug loading, controlled and sustained drug release, and increased permeability of poorly water-soluble drugs. These characteristics make them effective for targeted delivery in the treatment of chronic and complex conditions, such as cancer, infections, neurological disorders, diabetes, hypertension, and pain management. Additionally, their application in gel-based formulations supports long-term treatment of skin and wound-related disorders. Conclusion: Due to their biocompatibility, stability, and versatility, NLCs represent a promising platform for innovative drug delivery. However, comprehensive clinical evaluation of their long-term safety, toxicity, and bio-compatibility is essential. This review highlights the structure, classification, ingredients, formulation methods, and recent advancements in NLC technology, underlining their growing role in modern therapeutics. http://pbr.mazums.ac.ir/article-1-678-en.pdf 2025-03-19 81 94 10.32598/PBR.11.2.1378.1 Nanocarrier Lipid Bioavailability Lipid Nanocarriers (LNCs) Solid lipid nanoparticles (SLNs) Shivam Singh shivamchotu08@gmail.com 1 Department of Pharmaceutics, Seth Vishambhar Nath Institute of Pharmacy, Lucknow, India. AUTHOR https://orcid.org/0009-0002-0308-226X Arpita Singh arpitmohan2010@gmail.com 2 Department of Pharmaceutics, Seth Vishambhar Nath Institute of Pharmacy, Lucknow, India. AUTHOR https://orcid.org/0000-0002-8941-2348 Ritunja Singh ritunja4@gmail.com 3 Department of Pharmaceutics, Seth Vishambhar Nath Institute of Pharmacy, Lucknow, India. AUTHOR https://orcid.org/0009-0008-7526-3194 Anupama Maurya anupamamaurya1997@gmail.com 4 Department of Pharmaceutics, Seth Vishambhar Nath Institute of Pharmacy, Lucknow, India. AUTHOR https://orcid.org/0009-0001-2600-7863 Urmila Nishad nishadurmila1994@gmail.com 5 Department of Pharmaceutics, Seth Vishambhar Nath Institute of Pharmacy, Lucknow, India. AUTHOR https://orcid.org/0009-0005-5160-7851 Priyanka Tyagi tyagipriyanka20@gmail.com 6 Department of Pharmaceutics, Seth Vishambhar Nath Institute of Pharmacy, Lucknow, India. AUTHOR https://orcid.org/0009-0002-5610-4813 Harshit Yadav harshityadav31081997@gmail.com 7 Department of Pharmaceutics, Seth Vishambhar Nath Institute of Pharmacy, Lucknow, India. AUTHOR https://orcid.org/0009-0001-0703-564X

ORIGINAL_ARTICLE Background: Diabetes mellitus (DM) and hypertension often coexist in sufferers, which exacerbates the complications of DM. Also, the impacts of antihypertensive medications on the treatment outcomes of DM are not fully understood.  Objectives: Our objective was to evaluate the effect of valsartan and amlodipine on the hematological and biochemical differentials of vildagliptin-treated streptozotocin-induced diabetic rats.  Methods: DM was induced in male Wistar rats by a single intraperitoneal dose of streptozotocin (40 mg/kg body weight). The animals were grouped as non-diabetic rats (control), untreated diabetic rats, and diabetic rats treated with 5 mg/kg vildagliptin only, 5 mg/kg plus 30 mg/kg of vildagliptin and valsartan, respectively, and 5 mg/kg plus 2.5 mg/kg of vildagliptin and amlodipine, respectively. Drugs were administered orally, and rats were treated daily for three weeks. Then, blood samples were collected for hematological and biochemical analyses.  Results: The addition of amlodipine and valsartan as adjuncts to vildagliptin appeared to alter the evaluated differentials compared to vildagliptin treatment alone. Furthermore, the assessment of renal and liver functions, as well as the lipid profile, showed that treatment with valsartan as an adjunct improved the outcomes.  Conclusion: Our findings therefore suggest that amlodipine and valsartan brought about significant alterations in the differentials of diabetic rats treated with vildagliptin.  http://pbr.mazums.ac.ir/article-1-651-en.pdf 2025-03-19 95 104 10.32598/PBR.11.2.671.3 Diabetes mellitus (DM) Hypertension Vildagliptin Amlodipine Valsartan Israel Olapeju Bolanl 1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin City, Nigeria. AUTHOR https://orcid.org/0000-0002-4638-6522 Osayemwenre Erharuyi osayemwenre.erharuyi@uniben.edu 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Benin, Benin City, Nigeria. AUTHOR https://orcid.org/0000-0002-9667-2439 Abigail M. Akhigbemen abigail.omo-isibor@uniben.edu 3 Department of Pharmacy, University of Benin Teaching Hospital, University of Benin, Benin City, Nigeria. AUTHOR https://orcid.org/0000-0001-9412-5565 Amenaghawon Imuetinyan Ugiagbe ugiagbeamenaghawon@gmail.com 4 Department of Pharmacy, University of Benin Teaching Hospital, University of Benin, Benin City, Nigeria. AUTHOR Edobor Ekugum edis55ng@gmail.com 5 Department of Pharmaceutical Technology, Edo State Polytechnic Usen, Usen, Nigeria. AUTHOR Samuel O. Nwusulor ozoemenanwusulor@gmail.com 6 Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin City, Nigeria. AUTHOR Keziah E. Adudu keziahadudu@gmail.com 7 Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin City, Nigeria. AUTHOR Abiodun Falodun faloabi@uniben.edu 8 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Benin, Benin City, Nigeria. AUTHOR https://orcid.org/0000-0003-2929-3305

ORIGINAL_ARTICLE Background: The search for more active and less toxic anti-inflammatory drugs is the desire of every medicinal chemist. Amide derivatives of fatty acids (FAs) have diverse biological functions. Objectives: The search for more active and less toxic anti-inflammatory drugs is the desire of every medicinal chemist. Amide derivatives of FAs have diverse biological functions. Methods: The current study conducted an in-silico molecular docking analysis using PDB ID: 6DII on synthesized amide derivatives of long-chain FAs (LCFAs) and evaluated and correlated their anti-inflammatory and anti-nociceptive biological mechanisms with those of acetylsalicylic acid as a standard. The synthesis was achieved using glycine, β-alanine, γ-aminobutyric acid (GABA), and palmitoyl chloride. The raw paw edema model was used to assess the anti-inflammatory and analgesic properties.  Results: The anti-inflammatory assessment revealed a dose-dependent bioactivity from 20 mg/kg to 50 mg/kg; further increments in the dose led to decreased activity. For the analgesic activity, at 100 mg/kg, N-palmitoyl glycine exhibited 83.2% inhibition of writhing compared to 74.3% inhibition of the standard drug, aspirin (100 mg/kg). The molecular docking studies showed that N-palmitoyl alanine had the highest protein binding affinity, followed by N-palmitoyl, GABA, and N-palmitoyl glycine, higher than acetylsalicylic acid. The compounds interacted with the protein via specific functional groups and protein amino acid residues. Conclusion: The ability of these amide derivatives of LCFAs to biologically inhibit the inflammatory and nociceptive pathways could be attributed to the presence of N-H, C=O, and OH groups, which bind to the GLY-255, THR-300, GLY-302, and ASP-207 residues. http://pbr.mazums.ac.ir/article-1-666-en.pdf 2025-03-19 105 114 10.32598/PBR.11.2.820.2 Nociception Anti-inflammatory Agents Nociceptive Carrageenan-induced edema Molecular mechanisms Samuel J. Bunu amuelbunu2@gmail.com 1 Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, Niger Delta University, Wilberforce Island, Nigeria. AUTHOR https://orcid.org/0000-0001-5347-9383 Haruna Baba babharun1@gmail.com 2 Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Calabar, University of Calabar, Nigeria. AUTHOR https://orcid.org/0000-0001-7604-8703 Deghinmotei Alfred-Ugbenbo audeghinmotei@gmail.com 3 Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Bayelsa Medical University, Yenagoa, Nigeria. AUTHOR https://orcid.org/0000-0003-4835-1638

ORIGINAL_ARTICLE Background: Cyperus papyrus has been used to treat various health problems, such as ulcers and inflammation. Its possible use to promote healing, especially in the case of wounds, is still a topic that lacks thorough research.  Objectives: This study assessed the wound-healing effect of the ethanolic extract of C. papyrus in Wistar rats using an excision wound model.  Methods: The ethanolic extract of C. papyrus was made into gels at concentrations of 5% and 10%. Excisional wounds were induced on the dorsal of Wistar rats, which were treated topically with the gels twice daily. The effects of the treatment were evaluated through macroscopic measurements of wound contraction daily, histopathological analysis, and regeneration assessment by day 14.  Results: Wounds treated with C. papyrus gel at both concentrations of 5% and 10% showed increased rates of wound contraction when compared to the control group and the 10% formulation showed the most pronounced effect. Staining identifiable changes were noted that suggested enhanced epithelialization, advanced collagen maturation, inflammatory exocytosis within lower ranges of collagen deposition in the left interstitial tissue, and a decrease in the remaining inflammatory cells.  Conclusion: Using a 10% gel of C. papyrus extract through a topical procedure may increase the rate of wound healing in rats. This is probably due to the anti-inflammatory and antioxidant effects of the extract. These results confirm its effectiveness for further development of herbal therapeutic medicines to promote wound healing.  http://pbr.mazums.ac.ir/article-1-639-en.pdf 2025-03-19 115 124 10.32598/PBR.11.2.1021.4 Cyperus papyrus Healing of wounds Extracts of herbs Model of excision Mohammed Ali Khalifa Ahmed mmali198939@oiu.edu.sd 1 Department of Pharmacology, Faculty of Pharmacy, Omdurman Islamic University, Khartoum, Sudan. AUTHOR https://orcid.org/0000-0002-0766-6847 Amna Elhassan Hamad Mohammad amna.elhassan@gmail.com 2 Department of Pharmacology, Medicinal and Aromatic Plants and Traditional Medicine Research Institute, National Centre for Research, Khartoum, Sudan. AUTHOR https://orcid.org/0000-0001-9174-3472 Basher Mohamed Ahmed b.eltegani@gmail.com 3 Department of Pharmacology, Medicinal and Aromatic Plants and Traditional Medicine Research Institute, National Centre for Research, Khartoum, Sudan. AUTHOR https://orcid.org/0000-0003-4005-6802 Bashir A. Yousef 4 Department of Pharmacology, Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan. AUTHOR

ORIGINAL_ARTICLE Background: Parkinson’s disease (PD) is a neurodegenerative disorder marked by dopaminergic neuron loss, oxidative stress, and neuroinflammation, leading to progressive motor dysfunction. Current treatments provide symptomatic relief but do not halt disease progression. Caffeine, a widely consumed neurostimulant, has been linked to a reduced risk of PD and possesses antioxidant and anti-inflammatory properties.  Objectives: We investigated the effects of caffeine on motor performance, biochemical markers, and immunohistochemical changes in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced model of PD in female Swiss mice.  Methods: Twenty-five female mice were used, with 20 injected intraperitoneally (ip) with MPTP to induce PD. The mice were divided into five groups (n=5): Healthy controls, MPTP-induced PD, L-Dopa, 10 mg/kg caffeine, and 5 mg/kg caffeine for three weeks. Behavioral tests, including the pole test, beam test, and open field maze assessed motor activity and anxiety. Brain, liver, and heart tissues were analyzed for antioxidant, inflammatory, and oxidative stress markers. Brain tissues were also examined for immunohistochemistry, assessing microglial activation, TH, and α-synuclein to measure dopamine loss.  Results: Caffeine administration significantly (P<0.05) improved motor performance and decreased anxiety compared to MPTP-induced mice. Biochemical analyses of brain tissue showed that caffeine enhanced antioxidant activity by increasing the levels of catalase and glutathione while decreasing malondialdehyde (MDA), a marker of oxidative stress. Caffeine also significantly reduced the levels of pro-inflammatory cytokines, TNF-α, and IL-1α in the brain tissue, indicating an anti-inflammatory effect. Serum biochemical analyses indicated increased superoxide dismutase (SOD) levels, elevated catalase activity, and reduced MDA levels in caffeine-treated groups. Immunohistochemical analysis revealed a significant reduction in the expression of α-synuclein and microglial activation and preservation of TH-positive dopaminergic neurons in the substantia nigra following caffeine treatment.  Conclusion: Caffeine exerts protective effects against motor dysfunction, oxidative stress, and neuroinflammation in an MPTP-induced model of PD, highlighting its potential as a therapeutic agent for managing PD.  http://pbr.mazums.ac.ir/article-1-667-en.pdf 2025-03-19 125 138 10.32598/PBR.11.2.1251.1 Caffeine Parkinson’s disease (PD) Neuroprotection Oxidative stress Neuroinflammation Aminat Omolola Imam-Fulani imamfulani.ao@unilorin.edu.ng 1 Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. AUTHOR https://orcid.org/0000-0003-1359-7945 Abdulrahman Olanrewaju Shuaib aoshuaib@alhikmah.edu.ng 2 Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. AUTHOR https://orcid.org/0009-0008-3221-8385 Lateefah Omotoyosi Olajide latolajide@gmail.com 3 Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. AUTHOR https://orcid.org/0000-0002-4123-9013 Halimat Oluwakemi Afolabi afolabihalimat27@gmail.com 4 Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. AUTHOR https://orcid.org/0009-0002-5871-7744 Jerry Inyang jerprog0@gmail.com 5 Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. AUTHOR https://orcid.org/0009-0006-7815-1337 Oluwadamilola Onoshi Onoshi damilolaonoshi06@gmail.com 6 Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. AUTHOR https://orcid.org/0009-0002-9107-9457 Taofeekat Temitope Ogunsesan temitopetaofeekat@gmail.com 7 Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. AUTHOR https://orcid.org/0009-0003-4904-4514 Oyindamola Bisola Adekunle adeoyin97@gmail.com 8 Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. AUTHOR https://orcid.org/0009-0007-8352-0261 Taiwo Elijah Eso teezy577@gmail.com 9 Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. AUTHOR https://orcid.org/0009-0008-4363-4579 Oluwaseyi Deborah Babatunde oluwafunmilayodebbie24@gmail.com 10 Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. AUTHOR https://orcid.org/0009-0000-0904-2328 Edwin Ayolola Makanjuola Edwinmakanjuola@gmail.com 11 Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. AUTHOR Olamilekan Abdulfatai Alimi olamilekanola18@gmail.com 12 Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. AUTHOR https://orcid.org/0009-0005-1580-8752 Hafeez Ajibola Olorunoje hafeezolorunoje@gmail.com 13 Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. AUTHOR https://orcid.org/0009-0008-4116-9087 Kamaldeen Olalekan Sanusi sanusikamaldeen@yahoo.com 14 Department of Human Physiology, Faculty of Basic Medical Sciences, Al-Hikmah University, Ilorin, Nigeria. AUTHOR https://orcid.org/0000-0002-9588-7710

ORIGINAL_ARTICLE Background: Hypertension is a major public health concern worldwide, contributing to cardiovascular morbidity and mortality. The use of plant-based therapies, such as Euphorbia hirta and Leptadenia hastata, has gained attention for their potential antioxidant, anti-hyperlipidemic, and organ-protective effects.  Objectives: This study aimed to investigate the phytotherapeutic approach to hypertension using E. hirta and L. hastata extracts in adrenaline-induced hypertensive Wistar rats Methods: Utilizing an adrenaline-induced hypertensive rat model, we assessed the effects of E. hirta and L. hastata leaf extracts (50, 100, and 200 mg/kg) on systolic blood pressure, renal function, lipid metabolism, and hematological parameters. Results: Antioxidant activity: Increased levels of superoxide dismutase, catalase, and glutathione peroxidase. Lipid profiles: Reduced levels of total cholesterol, triglycerides, and LDL cholesterol. Liver function tests (LFTs): Decreased levels of alanine transaminase and aspartate transaminase. Hematological parameters: Improved red blood cell count, hemoglobin, and packed cell volume (PCV). Conclusion: This preclinical investigation provides compelling evidence for the antihypertensive potential of E. hirta and L. hastata leaf extracts, validating their traditional use. These findings underscore the promise of these natural products as adjunctive therapeutics for hypertension management, warranting further clinical investigation. http://pbr.mazums.ac.ir/article-1-659-en.pdf 2025-03-19 139 146 10.32598/PBR.11.2.1365.1 Antihypertensive Euphorbia hirta Leptadenia hastata traditional medicine Cardiovascular disorders Phytotherapy Cardiovascular Bushirat Oyenike Fagbohun bushirathassan@gmail.com 1 Department of Pharmacy Technician, Ogun State College of Health Science and Technology, Ogun, Nigeria. AUTHOR https://orcid.org/0009-0008-5853-567X Ochonung Emmanuel Ogar ochonungemmanuel1@gmail.com 2 Department of Chemical Engineering, University of Benin, Benin City, Nigeria. AUTHOR https://orcid.org/0009-0006-1665-9776 Atapia Innocent Messiah messiah.atapia@physci.uniben.edu 3 Department of Chemical Engineering, University of Benin, Benin City, Nigeria. AUTHOR https://orcid.org/0009-0001-4655-0935 Hassan Abdulsalam Adewuyi hasselbatch@gmail.com 4 Department of Biochemistry, Federal University of Technology, Minna, Nigeria. AUTHOR https://orcid.org/0009-0004-3824-5377 Waheed Sakariyau Adio waheedsackson@gmail.com 5 Department of Chemistry and Biochemistry, College of Science, Old Dominion University, Norfolk, United States. AUTHOR https://orcid.org/0000-0002-4546-0153 Adebimpe Hameedah Oluwatoyin adebimpehameedah@gmail.com 6 Department of Chemistry and Biochemistry, College of Health and Natural Sciences-Keplinger Hall, The University of Tulsa, Oklahoma, United States. AUTHOR Chizoba Victory Obunadike obunadikechizoba1234@gmail.com 7 Department of Industrial Chemistry, College of Pure and Applied Chemistry, Osun State University Osogbo, Osun, Nigeria. AUTHOR Adeleye Adegboyega Edema adeleye07edema@gmail.com 8 Department of Biochemistry, University of Ibadan, Oyo State Nigeria. AUTHOR https://orcid.org/0000-0001-7303-7283 Samad Hussein husseinsamad02@gmail.com 9 Department of Biochemistry, Federal University of Technology, Minna, Nigeria. AUTHOR Usman Abiola Mohammed abiolau@gmail.com 10 Department of Biological Sciences, AhmanPategi University, Pategi, Nigeria. AUTHOR Tolulope Olukayode Jaiyeola tolulope.jaiyeola@crawforduniversity.edu.ng 11 Department of Biological Sciences, Crawford University, Ketu Adieowe, Nigeria. AUTHOR https://orcid.org/0009-0003-8208-8404

ORIGINAL_ARTICLE Background: Tricyclic antidepressant (TCA) poisoning is a serious medical emergency due to its high toxicity and life-threatening complications. Objectives: This retrospective cross-sectional study evaluated the frequency of clinical, paraclinical, and prognostic findings of poisoned patients with TCAs who were referred to Shah Vali Hospital, Yazd, Iran, and Shahid Beheshti Hospital, Taft, Yazd, Iran, between 2014 and 2023. Methods: We collected neurological findings, cardiovascular findings, paraclinical findings, treatment measures, and prognosis of poisoned patients with TCA who were referred to Shah Vali Hospital in Yazd and Shahid Beheshti Hospital in Taft from 2014 to 2023. We examined the patient’s medical records to extract the findings.  Results: Over a decade-long study, 233 cases of poisoning resulting from TCAs were documented, with a mean age of 28.11 years. Most of these cases involved nortriptyline (42.5%) and amitriptyline (32.6%). Notably, 69.1% of the affected individuals were female. Neurological manifestations included agitation (42.9%), mydriasis (39.05%), and dryness of the skin and mucous membranes (52.3%). Additionally, seizures were reported in 10.7% of patients. Cardiovascular symptoms included shock in 6.2% of cases, tachycardia in 24.56%, and QRS complex prolongation in 14.16%. Elevated lead augmented vector right (aVR) was noted in 7.18% of patients, while rhabdomyolysis occurred in 7%. The primary treatment administered was sodium bicarbonate, utilized in 51.1% of cases. Furthermore, 8.2% of patients had a history of suicide attempts, predominantly associated with amitriptyline use. Ultimately, the mortality rate among this cohort was recorded at 1.7%. The findings suggested a significant association between different types of TCAs and factors, such as disease severity, rhabdomyolysis, gender, method of drug administration, and the occurrence of seizures (P=0.001). Additionally, a notable association was observed between mortality rates and QRS complex prolongation and rhabdomyolysis (P<0.001). Furthermore, a significant correlation was found between the frequency of QRS complex prolongation, seizures, and the necessity for tracheal intubation (P<0.01). However, no statistically significant association was found between mortality rates and gender and age (P<0.05). Conclusion: In conclusion, this study highlights that poisoning from TCAs remains a significant challenge in the management of poisoned patients across various regions. Nortriptyline and amitriptyline are the most commonly involved drugs in poisoning incidents, likely due to their widespread prescription in Iran. The observed higher prevalence of poisoning among women, coupled with the frequent occurrence of suicide attempts, underscores the necessity for addressing psychological factors and closely monitoring the use of these medications. Cardiac complications, particularly tachycardia and QRS complex prolongation on the ECG, are critical indicators of poisoning. Prompt treatment with sodium bicarbonate, along with effective management of severe conditions, such as seizures and hypotension, is essential to reduce mortality. Furthermore, a significant relationship exists between QRS complex prolongation and rhabdomyolysis about mortality outcomes. http://pbr.mazums.ac.ir/article-1-662-en.pdf 2025-03-19 147 158 10.32598/PBR.11.2.1366.3 TCA poisoning Tricyclic Antidepressant (TCA) poisoning Prognosis suicide Attempts nortriptyline poisoning Negar Zahir Mirdamadi negar.mrdd@gmail.com 1 Department of Toxicology, School of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. AUTHOR https://orcid.org/0009-0005-9493-3411 Hamid Reza Jamshidi hrz.jamshidi@gmail.com 2 Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. AUTHOR https://orcid.org/0000-0002-2739-2847 Khashayar Moravej 3 Faculty of Dentistry, Isfahan Branch, Islamic Azad University, Isfahan, Iran. AUTHOR https://orcid.org/0000-0002-4759-7516 Komeil Aghazadeh-Habashi komeil.aghazade@gmail.com 4 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. AUTHOR https://orcid.org/0000-0001-6002-2437 Sareh Rafatmagham Niloofarderavi@yahoo.com 5 Department of Internal Medicine, Fasa University of Medical Sciences, Fasa, Iran. AUTHOR https://orcid.org/0000-0002-2765-0543 Farhad Farnaghi drfarhadfarnaghi@gmail.com 6 Department of Toxicology, School of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. AUTHOR https://orcid.org/0000-0003-4266-2419 Hamid Reza Ghasemirad hr.ghasemirad@yahoo.com 7 Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. AUTHOR https://orcid.org/0000-0002-5390-6653 Raheleh Kadivari Rhlkdvri@gmail.com 8 Department of Medical Science, Faculty of Medicine, Yazd Branch, Islamic Azad University, Yazd, Iran. AUTHOR https://orcid.org/0000-0001-9774-0416 Hamid Owliaey hamid.owliaey@gmail.com 9 Department of Forensic Medicine & Clinical Toxicology, Faculty of Medicine, Yazd Branch, Islamic Azad University, Yazd, Iran. AUTHOR https://orcid.org/0000-0001-5642-9584

ORIGINAL_ARTICLE Background: Heavy metal accumulation has been shown to improve memory impairment, which is the most visible symptom of Alzheimer’s disease (AD).  Objectives: This study was conducted to select and synthesize rhodanine-N-acetic acid (ROD) ligand as an azosulpha drug, as well as its metal complexes containing Fe(III), Mn(III), and Cu(II), to evaluate the iron complex’s bioactivity in Swiss Albino rats. Methods: A new series of metal complexes were synthesized and characterized using elemental analysis, magnetic susceptibility, spectroscopic, and analytical methods, including Fourier-transform infrared spectroscopy (FT-IR), inductively coupled plasma (ICP), and thermogravimetric analysis (TG). The effects of heavy metal accumulation of the characterized iron complex on rats were investigated through in vivo studies.  Results: The results indicated that as the iron load in the liver and spleen tissues increased, the iron-binding capacity of the ROD ligand also significantly increased. Conclusion: These findings suggest that the activity of ROD metal complexes should be investigated further as a potential prodrug for AD. http://pbr.mazums.ac.ir/article-1-671-en.pdf 2025-03-19 159 172 10.32598/PBR.11.2.1373 Rhodanine Drug Alzheimer’s disease (AD) Iron Rats Elem Sabahsan ykaratas@cu.edu.tr 1 Department of Chemistry, Faculty of Arts and Science, Cukurova University, Adana, Turkey. AUTHOR https://orcid.org/0009-0001-7685-9167 Emel Yildiz eeyildiz@cu.edu.tr 2 Department of Chemistry, Faculty of Arts and Science, Cukurova University, Adana, Turkey. AUTHOR https://orcid.org/0000-0002-3169-491X Yusuf Karatas elemseflek@hotmail.com 3 Department of Medical Pharmacology, Faculty of Medicine, Cukurova University, Adana, Turkey. AUTHOR https://orcid.org/0000-0002-2892-5625