Iranian Journal of Pharmaceutical Research最新文献

{"title":"Protective Effect of Soy Lecithin Liposomes in Oxazolone-Induced Dermatitis in a Mouse Model: A Comparative Evaluation.","authors":"Alireza Partoazar, Maryam Alemi, Partow Mirzaee Saffari, Maryam Eskandary Nasab, Tayebeh Rastegar, Ahmad Reza Dehpour, Ramin Goudarzi","doi":"10.5812/ijpr-170144","DOIUrl":"10.5812/ijpr-170144","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense itching, severe erosion, and rashes on the skin surface. Prolonged AD may cause hemorrhage and secondary infections due to scratching.</p><p><strong>Objectives: </strong>This study aimed to investigate the anti-AD effects of soy lecithin (SL) applied topically to oxazolone (OX)-treated skin in a mouse model.</p><p><strong>Methods: </strong>The effects of SL and hydrocortisone (HC), used as the standard drug, on behavioral responses such as scratching and grooming were evaluated during a 35-day trial. Histopathology and immunohistochemistry (IHC) for the cytokines TNFα and IL8 were also evaluated in the skin of the treated mice.</p><p><strong>Results: </strong>Topical administration of SL showed efficacy comparable to that of HC and significantly alleviated itching and grooming behaviors in eczematous animals. Topical SL also improved symptoms, including skin erythema, scarring, and edema, as well as histopathological parameters in AD mice. IHC analysis indicated that SL administration effectively reduced tissue levels of the inflammatory cytokines TNFα and IL8 in AD mice.</p><p><strong>Conclusions: </strong>Topical SL significantly improved AD severity in an OX-induced mouse model of AD. These results support further preclinical studies before clinical investigations in humans are undertaken.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e170144"},"PeriodicalIF":1.7,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effect of Methoxsalen on Spinal Cord Injury in the Rat Model via Regulation of the PI3K/Akt Pathway.","authors":"Mao Zhaohu, Zhang Zheng, Shan Qunqun","doi":"10.5812/ijpr-171331","DOIUrl":"10.5812/ijpr-171331","url":null,"abstract":"<p><strong>Background: </strong>Spinal cord injury (SCI) is a major cause of disability, and the management of secondary injury remains challenging.</p><p><strong>Objectives: </strong>This study evaluated the protective effects of methoxsalen against SCI and investigated its potential mechanism of action.</p><p><strong>Methods: </strong>Network pharmacology and molecular docking were performed to identify the molecular targets of methoxsalen for the treatment of SCI. SCI was induced in rats by laminectomy, and methoxsalen (12 and 24 mg/kg, p.o.) was administered for 14 days after SCI induction. Motor function was assessed using the Basso, Beattie, and Bresnahan (BBB) score, and spinal cord inflammation was evaluated by assessing water deposition and inflammatory cytokine levels in SCI rats. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to assess the mRNA expression of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) in SCI rats.</p><p><strong>Results: </strong>Molecular docking data showed that methoxsalen interacted with AKT, PI3K, and nuclear factor-κB (NF-κB), with binding energies of -9.1, -9.2, and -9.4 kcal/mol, respectively. The BBB score was significantly improved in the methoxsalen-treated group compared with the SCI group. MDA (18.6 ± 0.9 nmol/mg) and ROS (1.30 ± 0.04-fold) levels were significantly reduced, whereas GSH (92.0 ± 2.2 µM/mg) and SOD (54.2 ± 1.3 U/mg) levels were increased in the methoxsalen-treated group compared with the SCI group. Methoxsalen treatment ameliorated inflammatory alterations and cytokine levels in rats with SCI. The mRNA expression of PI3K, AKT, and NF-κB was attenuated in spinal cord tissue from methoxsalen-treated rats with SCI.</p><p><strong>Conclusions: </strong>Methoxsalen treatment improved motor function in rats with SCI by modulating the PI3K/AKT signaling pathway.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e171331"},"PeriodicalIF":1.7,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiolabeling of Amberlite IRA-68 Resin Microspheres with Rhenium-188: Optimization and Biodistribution in Tumor-Bearing Mice Following Intratumoral Administration.","authors":"Zohreh Zavarzadeh-Moghaddam, Mehdi Salehi Barough, Leila Moghaddam-Banaem, Sodeh Sadjadi, Fariba Johari Daha","doi":"10.5812/ijpr-172717","DOIUrl":"10.5812/ijpr-172717","url":null,"abstract":"<p><strong>Background: </strong>Rhenium-188 (¹⁸⁸Re) is a therapeutic radionuclide with favorable nuclear properties, including high beta energy and a suitable half-life, making it attractive for radiopharmaceutical applications. Solid carriers, such as ion-exchange resins, may improve radionuclide stability, loading efficiency, and controlled delivery.</p><p><strong>Objectives: </strong>This study aimed to activate Amberlite IRA-68 anion-exchange resin microspheres, optimize their labeling with rhenium and ¹⁸⁸Re, and evaluate the biodistribution of the radiolabeled microspheres following intratumoral injection in tumor-bearing mice at 24 and 48 h post-administration.</p><p><strong>Methods: </strong>The effects of contact time, temperature, pH, and initial rhenium concentration on labeling efficiency were systematically investigated. Resin labeling was evaluated by elemental composition analysis using a scanning electron microscope (SEM) equipped with an energy-dispersive X-ray (EDX) analyzer. Radiochemical purity was assessed by instant thin-layer chromatography (ITLC). Activity distribution in mouse organs was assessed using the ISOMED 1010 dose calibrator.</p><p><strong>Results: </strong>The results demonstrated high labeling efficiency; under optimal conditions (rhenium initial concentration 10 ppm, pH 7, 25 °C, 120 min), rhenium uptake reached approximately 98%. Following intratumoral administration, the radiolabeled microspheres showed high tumor retention (5.39%ID/g at 24 h), whereas radioactivity in the blood and normal organs remained relatively low. This retention indicates localized persistence of the injected microspheres rather than active biological targeting. These findings support the potential of Amberlite IRA-68 resin microspheres as an effective carrier for ¹⁸⁸Re-based radiopharmaceutical applications.</p><p><strong>Conclusions: </strong>In this study, Amberlite IRA-68 anion-exchange resin microspheres were successfully evaluated as a carrier system for rhenium and rhenium-188. The results demonstrated high labeling efficiency, reaching approximately 98% under optimized conditions (10 ppm, pH 7, 25 °C, 120 min), indicating a strong affinity between the resin and perrhenate ions. The biodistribution study demonstrated that ¹⁸⁸Re-labeled Amberlite IRA-68 microspheres showed favorable in vivo characteristics following intratumoral administration. The radiopharmaceutical showed high tumor accumulation at 24 h (%ID/g = 5.39), with persistent retention at 48 h and low blood activity, indicating minimal systemic leakage and limited uptake in critical organs.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e172717"},"PeriodicalIF":1.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naringin Administration Is Associated with Reduced Reproductive Toxicity Following Subchronic Low-Dose Chlorpyrifos Exposure in Rats.","authors":"Solale Ramzani, Seyed Bagher Mortazavi, Mohammad Shokrzade, Ali Khavanin","doi":"10.5812/ijpr-169653","DOIUrl":"10.5812/ijpr-169653","url":null,"abstract":"<p><strong>Background: </strong>Male infertility is increasingly associated with environmental and occupational exposure to organophosphate pesticides, particularly chlorpyrifos (CPF). Chlorpyrifos persists in food, water, and the environment, resulting in chronic low-dose exposure. Although the toxic effects of high-dose exposure are well documented, the reproductive consequences of subchronic low-dose exposure remain unclear.</p><p><strong>Objectives: </strong>To evaluate whether intraperitoneal administration of naringin attenuates CPF-induced reproductive toxicity in adult male rats by assessing sperm parameters, serum reproductive hormones, oxidative stress markers, and testicular histopathology.</p><p><strong>Methods: </strong>Adult male rats were assigned to six groups (n = 5 per group): Control, naringin control (200 mg/kg), CPF (8 mg/kg), and CPF plus naringin (50, 100, or 200 mg/kg). Sperm count, motility, and morphology; serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels; testicular malondialdehyde, reactive oxygen species, glutathione, and superoxide dismutase levels; and histopathological changes were assessed.</p><p><strong>Results: </strong>Chlorpyrifos exposure was associated with impaired sperm count, motility, and morphology; reduced reproductive hormone levels; increased oxidative stress; and testicular histological damage. Naringin pretreatment was associated with dose-dependent improvements in sperm parameters, partial restoration of hormonal balance, improvement in oxidative stress markers, and preservation of testicular histology, with more pronounced effects at 100 and 200 mg/kg.</p><p><strong>Conclusions: </strong>Naringin administration was associated with attenuation of CPF-induced reproductive alterations and improved oxidative stress markers and hormonal parameters. These findings support further investigation of naringin for pesticide-induced male reproductive dysfunction; however, validation in humans is required. The limited range of naringin doses and the absence of molecular investigations highlight the need for further studies to elucidate the underlying mechanisms and translational relevance to human reproductive health.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169653"},"PeriodicalIF":1.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Preclinical Evaluation of 188Re-MAX-HEDP: A Promising Theranostics Strategy for Bone Metastases.","authors":"Sarah Shoohani, Saeed Kakaei, Elham Sattarzadeh Khameneh, Fariba Johari Daha, Mojtaba Tajik","doi":"10.5812/ijpr-170436","DOIUrl":"10.5812/ijpr-170436","url":null,"abstract":"<p><strong>Background: </strong>Bone-associated disorders, including metastatic bone lesions, osteoporosis, and pathological fractures, require agents that can support both diagnostic imaging and targeted therapy. Theranostic radiopharmaceuticals provide an integrated approach for disease detection and radionuclide therapy.</p><p><strong>Objectives: </strong>This study aimed to design, synthesize, radiolabel, and evaluate a novel bone-targeting theranostic radiopharmaceutical, ¹⁸⁸Re-MAX-HEDP, for potential diagnostic and therapeutic applications for bone-related diseases.</p><p><strong>Methods: </strong>A novel ligand, MAX-HEDP, was synthesized by conjugating hydroxyethylidene diphosphonic acid (HEDP) to the chelating moiety methoxy amido xanthate (MAX). The ligand was radiolabeled with rhenium-188 (¹⁸⁸Re). Labeling efficiency, chemical yield, in vitro stability under physiological conditions, and biodistribution in normal mice were evaluated.</p><p><strong>Results: </strong>The synthesis of MAX-HEDP achieved an overall chemical yield of 91%. Radiolabeling with ¹⁸⁸Re produced a highly stable complex, with a labeling efficiency exceeding 99%. Stability studies showed that more than 96% of the complex remained intact at ambient temperature, whereas degradation at 37 °C was less than 10%. Biodistribution studies demonstrated pronounced skeletal uptake of ¹⁸⁸Re-MAX-HEDP compared with uptake in other organs, confirming its strong bone-targeting potential.</p><p><strong>Conclusions: </strong>¹⁸⁸Re-MAX-HEDP demonstrated a high synthesis yield, excellent radiolabeling efficiency, favorable stability, and selective skeletal accumulation. These findings suggest that it is a promising, cost-effective theranostic candidate for further clinical evaluation in the diagnosis and radionuclide therapy of bone malignancies and other bone-associated disorders.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e170436"},"PeriodicalIF":1.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacophore-Based Virtual Screening for Identification of Adenosine Deaminase Inhibitors.","authors":"Saba Ahmadi, Mona Khoramjouy, Arefeh Jafarian, Soraya Shahhosseini, Salimeh Amidi, Farzad Kobarfard","doi":"10.5812/ijpr-170515","DOIUrl":"10.5812/ijpr-170515","url":null,"abstract":"<p><strong>Background: </strong>Adenosine deaminase (ADA) is a key enzyme in purine metabolism, and abnormal ADA activity has been associated with various diseases, including severe combined immunodeficiency, cancer, neurodegenerative disorders, and liver diseases.</p><p><strong>Objectives: </strong>This study employed a pharmacophore-based virtual screening strategy to identify novel ADA inhibitors from an in-house library.</p><p><strong>Methods: </strong>Two crystal structures of ADA co-crystallized with erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and pentostatin were used to develop a pharmacophore model. The validated model was used to screen an in-house library. The resulting hits were further evaluated using molecular docking with AutoDock Vina. The compound with the highest binding affinity in the docking study was subsequently assessed by molecular dynamics (MD) simulation and in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis.</p><p><strong>Results: </strong>The validated pharmacophore model comprised one hydrogen bond donor, one hydrogen bond acceptor, and one aromatic ring. When evaluated against the DUDE-Z database set, the model demonstrated acceptable sensitivity and specificity, with an enrichment factor of 23. Screening of the in-house library identified four promising hits. Compound 154 was the most notable hit because of its potent binding affinity and favorable interactions with key amino acids in the ADA active site. MD simulations showed that the ADA-compound 154 complex remained stable throughout the 150 ns simulation. MM-GBSA energy analysis indicated favorable binding driven by van der Waals and electrostatic interactions. Per-residue decomposition analysis identified critical residues contributing to complex stabilization. Compared with reference ADA inhibitors, compound 154 exhibited similar drug-likeness and pharmacokinetic properties, although further toxicity optimization may be required.</p><p><strong>Conclusions: </strong>These results suggest that compound 154 is a promising lead for developing new ADA inhibitors and underscore the effectiveness of computational methods in drug discovery.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e170515"},"PeriodicalIF":1.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Network Analysis of Bioactive Compounds from <i>Punica granatum</i> L. Peel: Multi-Target Mechanisms in Wound Healing.","authors":"Seyyed Shahab Shokri, Ebrahim Salimi Sabour, Seyed Morteza Hosseini, Hossein Reza Shateri","doi":"10.5812/ijpr-170416","DOIUrl":"10.5812/ijpr-170416","url":null,"abstract":"<p><strong>Background: </strong>Wound-healing agents often have limited efficacy and require prolonged recovery times, prompting growing interest in developing herbal-based formulations. Among these, <i>Punica granatum</i> L. has attracted considerable attention because of its high polyphenolic content. Despite its widespread use, the precise pharmacological targets underlying its wound-healing effects remain poorly understood and require systematic investigation.</p><p><strong>Objectives: </strong>This study aimed to elucidate the underlying pharmacological mechanisms of the topical wound-healing properties of <i>P. granatum</i> L. using a network pharmacology approach.</p><p><strong>Methods: </strong>Bioactive compounds of <i>P. granatum</i> L. and their potential target genes were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Similarity Ensemble Approach (SEA), and SwissTargetPrediction databases. Wound healing-related genes were retrieved from the GeneCards database. Genes intersecting <i>P. granatum</i> L. targets and wound healing-associated genes were subjected to functional enrichment analyses, including protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The PPI network was further analyzed using Cytoscape, and the phytoconstituent-target interaction network was visualized using Gephi. These findings were validated using molecular docking.</p><p><strong>Results: </strong>A total of 40 intersecting genes were identified as potential <i>P. granatum</i> L. targets involved in wound healing. Among these, EGFR, PTPN11, HRAS, IGF1R, and ESR1 were identified as key hub genes. Functional enrichment analysis indicated that the most significantly enriched signaling pathways included the MAPK, PI3K-Akt, EGFR tyrosine kinase inhibitor resistance, focal adhesion, and FoxO signaling pathways. Molecular docking analysis confirmed favorable binding of quercetin and ellagic acid to the hub targets EGFR, IGF1R, and ESR1.</p><p><strong>Conclusions: </strong>These findings elucidate the pharmacological pathways underlying <i>P. granatum</i>-mediated wound healing and suggest that <i>P. granatum</i> L. acts as a multi-target modulator in the wound-healing process.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e170416"},"PeriodicalIF":1.7,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Evaluation of the Effects of Nanoparticles of Atorvastatin and Atorvastatin on Cuprizone-Induced Demyelination: Modulation of the Nrf2/NF-kB Signaling Pathway.","authors":"Samira Shirooie, Niloofar Heidarizade, Tayebeh Noori, Antoni Sureda, Amin Iranpanah, Sina Alibeygi","doi":"10.5812/ijpr-170319","DOIUrl":"10.5812/ijpr-170319","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by damage to the myelin sheath and, over time, by progressive neurological disability. Statins have attracted attention in MS research owing to their anti-inflammatory and neuroprotective effects.</p><p><strong>Objectives: </strong>This study assessed whether atorvastatin could ameliorate cuprizone-induced behavioral and histopathological changes in the brains of male C57BL/6 mice.</p><p><strong>Methods: </strong>All groups of mice, except the control group, which received a normal diet, were fed 0.2% cuprizone (CPZ) in their daily diet for 6 weeks to induce demyelination. The treatment groups received atorvastatin (1, 2, or 4 mg/kg/day, i.p.) or nano-atorvastatin (2 mg/kg/day, i.p.) during the final 2 weeks of the study. At the end of the study, behavioral tests were conducted, and immunofluorescence assessment of NF-kB p65 and Nrf2 in the corpus callosum was conducted.</p><p><strong>Results: </strong>CPZ caused progressive weight loss by the end of the study compared with the control group; this effect was reversed by treatment with atorvastatin and nano-atorvastatin. All behavioral tests showed reduced motor coordination in the CPZ group (P < 0.001) compared with the control group. Administration of atorvastatin and nano-atorvastatin during the last 2 weeks reversed these motor deficits. Histopathological examination showed significant demyelination in the CPZ group, which was reversed by atorvastatin injections. Furthermore, CPZ significantly decreased Nrf2 levels (P < 0.001) and increased NF-kB p65 levels (P < 0.001) in the corpus callosum; these changes were stabilized in the atorvastatin and nano-atorvastatin groups.</p><p><strong>Conclusions: </strong>Atorvastatin may attenuate CPZ-induced toxicity by reducing demyelination and modulating the NF-kB p65 and Nrf2 signaling pathways.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e170319"},"PeriodicalIF":1.7,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effects of Empagliflozin Against Methamphetamine-Induced Withdrawal Syndrome in Mice: Involvement of Bdnf, Tlr4, and JNK Signaling Pathways and Oxidative Stress Biomarkers.","authors":"Hamed Ghavimi, Mina Ebrahimi, Maede Hasanzadeh, Alireza Lashgari, Keivan Nedaei, Ali Kalantari Hesari, Mir-Jamal Hosseini","doi":"10.5812/ijpr-172023","DOIUrl":"10.5812/ijpr-172023","url":null,"abstract":"<p><strong>Background: </strong>Methamphetamine withdrawal is associated with reduced dopaminergic neurotransmission, oxidative stress, neuroinflammation, and structural brain changes, which are linked to cognitive impairment, memory deficits, and psychological distress.</p><p><strong>Objectives: </strong>This study investigated whether empagliflozin, a sodium-glucose cotransporter 2 inhibitor, mitigates behavioral, molecular, and histopathological alterations induced by chronic methamphetamine (METH) exposure.</p><p><strong>Methods: </strong>Eighty male NMRI mice were allocated to 8 groups (n = 10). Methamphetamine dependence was induced by administering 2 mg/kg intraperitoneally, twice daily, for 14 days. During METH withdrawal, mice received empagliflozin (0.5, 1, 2, or 10 mg/kg, orally) or saline for 10 days. From days 25 to 28, the open-field test, forced swimming test, elevated plus maze, and novel object recognition test were conducted to assess depression-like behavior, anxiety-like behavior, and cognition. On day 28, the hippocampi were isolated and evaluated for oxidative and antioxidant biomarkers, nitric oxide (NO), and the expression of toll-like receptor 4 (Tlr4), brain-derived neurotrophic factor (Bdnf), and c-Jun N-terminal kinase (JNK). Histopathological studies of the hippocampus and prefrontal cortex were also performed using hematoxylin and eosin staining.</p><p><strong>Results: </strong>Methamphetamine withdrawal induced pronounced anxiety-like and depression-like behaviors, recognition memory impairment, redox imbalance, upregulation of Tlr4 and JNK, suppression of Bdnf, and inflammation. However, post-withdrawal empagliflozin ameliorated affective and cognitive deficits, restored glutathione and ferric-reducing antioxidant power, reduced malondialdehyde and protein carbonyl levels, normalized tissue NO levels, increased Bdnf expression, downregulated Tlr4 and JNK expression, and markedly reversed histopathological damage. These findings suggest that empagliflozin confers robust behavioral, antioxidant, anti-inflammatory, and neuroprotective effects during methamphetamine withdrawal.</p><p><strong>Conclusions: </strong>The results of this animal study support empagliflozin as a potential treatment for neuropsychiatric dysfunction associated with METH withdrawal. Further clinical studies are needed to confirm the effects of empagliflozin.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e172023"},"PeriodicalIF":1.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silymarin Exerts Potent Antipruritic Effects Against Chloroquine-Induced Scratching in Mice by Modulating the NO/NF-κB/TRPA1 Pathway.","authors":"Hosna Bagheri, Amir Kiani, Mohammad Amin Ali Mohammad Golesorkhi, Antoni Sureda, Samira Shirooie","doi":"10.5812/ijpr-169711","DOIUrl":"10.5812/ijpr-169711","url":null,"abstract":"<p><strong>Background: </strong>Pruritus may occur through histamine-dependent or histamine-independent mechanisms. Chronic pruritus, which is often unresponsive to antihistamines, has been associated with nitric oxide (NO) signaling, which can modulate nuclear factor-κB (NF-κB) activity and transient receptor potential ankyrin 1 (TRPA1) function.</p><p><strong>Objectives: </strong>This study investigated the antipruritic potential of silymarin in a mouse model of chloroquine-induced systemic pruritus.</p><p><strong>Methods: </strong>Adult male NMRI mice were allocated to 16 groups. Treatments included silymarin (10, 30, and 60 mg/kg), L-NAME (1 and 10 mg/kg), aminoguanidine, L-arginine (10 and 100 mg/kg), sildenafil (10 and 20 mg/kg), and various combinations of these agents with silymarin. Scratching behavior, including frequency and duration, was recorded for 30 minutes on the second day after chloroquine (CQ) administration. Dorsal root ganglia (DRG) were analyzed by immunofluorescence to assess the expression of NF-κB and TRPA1.</p><p><strong>Results: </strong>Silymarin (60 mg/kg), L-NAME (10 mg/kg), and aminoguanidine significantly reduced chloroquine-induced itching, whereas L-arginine (100 mg/kg) and sildenafil (20 mg/kg) exacerbated it. The combination of subeffective doses of L-NAME (1 mg/kg) and silymarin (10 mg/kg) produced potentiated antipruritic effects, whereas L-arginine and sildenafil counteracted the inhibitory effects of high-dose silymarin. CQ increased NF-κB and TRPA1 expression in the DRG. These changes were ameliorated by silymarin and L-NAME but aggravated by L-arginine and sildenafil.</p><p><strong>Conclusions: </strong>Silymarin alleviated chloroquine-induced itching, suggesting modulation of the NO/NF-κB/TRPA1 signaling pathway and supporting its potential as a therapeutic option for histamine-independent pruritic conditions.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169711"},"PeriodicalIF":1.7,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}