Iranian Journal of Pharmaceutical Research最新文献

{"title":"Evaluation of the Protective Effect of a Well-Characterized n-Hexane Extract of Black Soldier Fly Larvae (<i>Hermetia illucens</i>) Against Acrylamide-Induced Testicular Damage in Male Rats: A Histopathological, Oxidative Stress, Inflammatory, and Molecular Study.","authors":"Fateme Heidari, Tahereh Zarei Taher, Yalda Arast","doi":"10.5812/ijpr-173454","DOIUrl":"10.5812/ijpr-173454","url":null,"abstract":"<p><strong>Background: </strong>Acrylamide (ACR) is a ubiquitous contaminant present in environmental and dietary sources and is formed particularly in starchy foods during high-temperature processing. Prolonged exposure to ACR is associated with testicular dysfunction mediated by oxidative injury, inflammatory responses, and apoptotic cell death. Black soldier fly larvae (BSFL; <i>Hermetia illucens</i>) represent a sustainable source of bioactive lipids, notably lauric acid, which has recognized antioxidant and anti-inflammatory properties. Importantly, BSFL can be cultivated on organic waste, converting low-value materials into lipid-enriched biomass with therapeutic potential, consistent with the principles of the circular economy.</p><p><strong>Objectives: </strong>This study was designed, for the first time, to investigate the protective potential of a chemically characterized n-hexane extract of BSFL against acrylamide-induced testicular toxicity in a rat model.</p><p><strong>Methods: </strong>Thirty-five adult male Wistar rats were allocated to five experimental groups (n = 7 per group): vehicle control, ACR (20 mg/kg), ACR plus BSFL180 (180 mg/kg), ACR plus BSFL360 (360 mg/kg), and BSFL360 alone. All treatments were administered orally for 28 consecutive days. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and dihydrotestosterone (DHT) were measured. Testicular specimens were analyzed for oxidative stress markers (malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], reduced glutathione [GSH]), inflammatory cytokines (TNF-α, IL-6, IL-1β), and apoptosis-related proteins (Nrf2, Bcl-2, Bax). Histological assessment was performed using H&E staining.</p><p><strong>Results: </strong>ACR administration markedly reduced serum FSH, LH, and DHT levels; increased MDA and pro-inflammatory cytokine levels; suppressed antioxidant enzyme activities and GSH content; and induced severe histopathological damage. Co-administration of BSFL extract, particularly at 360 mg/kg, dose-dependently counteracted these detrimental effects. Western blot analysis showed that BSFL extract upregulated Nrf2 and Bcl-2 expression while downregulating Bax, thereby restoring the Bax/Bcl-2 balance. The extract alone produced no adverse effects.</p><p><strong>Conclusions: </strong>The n-hexane extract of BSFL exerts substantial protective effects against ACR-induced testicular toxicity by restoring hormonal balance, mitigating oxidative stress, suppressing inflammation, and modulating Nrf2 and Bax/Bcl-2 signaling. These findings highlight the therapeutic potential of BSFL as a sustainable, cost-effective natural product within a circular bioeconomy framework and a novel approach to preventing chemically induced testicular injury.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e173454"},"PeriodicalIF":1.7,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008446","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":"Development and Validation of an LC-MS/MS-Based Screening Method for Determination of Salbutamol in Urine for Doping Control Using a Surrogate Analyte Approach with Stable Isotope-Labeled Salbutamol (Salbutamol-d9).","authors":"Zeinab Srour, Farzad Kobarfard, Zahra Sheikholislam, Mehrdad Faizi, Bahram Daraei","doi":"10.5812/ijpr-169531","DOIUrl":"10.5812/ijpr-169531","url":null,"abstract":"<p><strong>Background: </strong>Athletic doping has long received attention in the sports community. Salbutamol is prohibited by the World Anti-Doping Agency (WADA) both in and out of competition, with a urinary concentration threshold of 1000 ng/mL defining the legal limit. Traditional liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical methods that use an internal standard cannot fully overcome matrix effects and biological variation, requiring revalidation for different biological samples; this process can be time-consuming and can remain prone to matrix-related errors.</p><p><strong>Objectives: </strong>To develop a novel approach for screening salbutamol in urine that overcomes the limitations of traditional LC-MS/MS methods and improves analytical reliability and efficiency across biological matrices.</p><p><strong>Methods: </strong>A surrogate analyte-based LC-MS/MS method was developed for the quantitative determination of salbutamol in human urine, using salbutamol-d9 as a stable isotope-labeled surrogate analyte. During method optimization, concentrations ranging from 1 ppm to 0.1 ppb were analyzed in aqueous and urine samples to evaluate extraction efficiency, purification, and matrix effects. Molar-equivalent concentrations of unlabeled salbutamol (1000 ng/mL, the WADA legal limit) and labeled salbutamol (1039 ng/mL) were analyzed in both matrices to validate the surrogate analyte approach and confirm comparable peak areas. To evaluate the applicability of the method, urine samples were collected from healthy volunteers after oral administration of 4 mg salbutamol. All samples were extracted under alkaline conditions using liquid-liquid extraction and analyzed by LC-MS/MS in positive-ion mode with multiple reaction monitoring (MRM). The labeled compound served as a reference for interpretation of the results. Method validation was performed according to international guidelines, including assessments of linearity, precision, accuracy, and sensitivity.</p><p><strong>Results: </strong>The method demonstrated excellent linearity (R² > 0.99), with intra- and inter-day precision within 8% RSD and acceptable accuracy. The limits of detection (LOD) and quantification (LOQ) were 0.3 and 1 ng/mL, respectively. Analysis of urine from healthy volunteers following a 4 mg oral dose confirmed reliable quantification for up to 24 hours, demonstrating applicability to biological matrices.</p><p><strong>Conclusions: </strong>These findings indicate that this isotope-based surrogate analyte approach eliminates the need for calibration curves, compensates for matrix effects and sample preparation errors, and improves analytical reliability and efficiency across biological matrices.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169531"},"PeriodicalIF":1.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008284","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":"Lyoniresinol Improves Insulin Sensitivity and Induces White-to-Beige Adipose Tissue Conversion in Obese Rats: Associated with JNK/PI3K/mTOR Pathway Modulation.","authors":"Wen Lei, Alok Tripathi, Shuwen Hu","doi":"10.5812/ijpr-171105","DOIUrl":"10.5812/ijpr-171105","url":null,"abstract":"<p><strong>Background: </strong>Obesity contributes to multiple chronic diseases and remains a critical global health challenge.</p><p><strong>Objectives: </strong>This study evaluated the therapeutic effects of lyoniresinol on high-fat diet-induced obesity and its underlying molecular mechanisms.</p><p><strong>Methods: </strong>Network pharmacology was used to identify potential targets of lyoniresinol in obesity treatment, followed by validation using molecular docking. High-fat diet-induced obese rats received lyoniresinol (30 mg/kg/day) for six weeks. The primary efficacy endpoints were insulin sensitivity, assessed by the oral glucose tolerance test (OGTT), insulin tolerance test (ITT), fasting glucose, and fasting insulin, and adiposity measures, including body weight and regional fat mass. The key secondary endpoint was uncoupling protein 1 (UCP1) expression in adipose tissue, evaluated by Western blotting and immunohistochemistry. Mechanistic validation comprised analysis of the phosphorylation status of c-Jun N-terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K), and mammalian target of rapamycin (mTOR) by Western blotting. Exploratory assessments included serum lipid profiles, inflammatory cytokines, oxidative stress biomarkers, and histopathological examination.</p><p><strong>Results: </strong>Network pharmacology identified 50 shared targets between lyoniresinol and obesity. Molecular docking indicated favorable binding to JNK, PI3K, and mTOR. For the primary endpoints, lyoniresinol treatment was associated with reduced body weight gain, restored normoglycaemia, enhanced insulin sensitivity, and decreased regional adipose tissue mass. For the key secondary endpoint, UCP1 expression was upregulated, suggesting the browning of white adipose tissue. For the exploratory endpoints, lyoniresinol was associated with improved dyslipidaemia, reduced oxidative stress, suppressed pro-inflammatory cytokines and C-reactive protein (CRP), and attenuated adipocyte hypertrophy. For mechanistic validation, lyoniresinol treatment was associated with suppressed JNK phosphorylation and activation of PI3K/mTOR signaling in adipose tissue, suggesting potential involvement of the JNK/PI3K/mTOR pathway in these effects.</p><p><strong>Conclusions: </strong>Based on the primary efficacy endpoints, lyoniresinol was associated with improved insulin sensitivity and reduced adiposity in obese rats. The key secondary endpoint (UCP1 upregulation) and mechanistic validation (altered JNK/PI3K/mTOR phosphorylation) further support its association with the browning of white adipose tissue. These findings suggest that lyoniresinol may represent a multi-target candidate for further investigation in obesity-related metabolic disorders; however, the precise molecular mechanisms require additional validation.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e171105"},"PeriodicalIF":1.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008460","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":"S-Allyl Cysteine Accumulation Depends on Temperature and Aging Duration of an <i>Allium</i> Organosulfur Compound Blend (<i>Allium sativum</i>).","authors":"Shiva Shamshiri, Mehran Mirabzadeh Ardekani, Hamid Reza Moghimi, Ehsan Sadeghnezhad","doi":"10.5812/ijpr-167972","DOIUrl":"10.5812/ijpr-167972","url":null,"abstract":"<p><strong>Background: </strong>Garlic (<i>Allium sativum</i>) is an important medicinal plant, and its therapeutic properties are primarily attributed to its organosulfur compounds (OSCs). However, the development of medicinal garlic-based formulations remains challenging because of the inherent instability of these bioactive compounds. Traditional garlic-based formulations may provide a suitable matrix for promoting the conversion of unstable sulfur compounds into more stable derivatives during aging.</p><p><strong>Objectives: </strong>This study investigated the time-dependent chemical transformations of major garlic-derived organosulfur compounds in Ma'joun Soum, a traditional Iranian garlic-based semisolid formulation prepared according to Qarabadin-e-Kabir. During a 30-day storage period, the effects of different aging processes on the concentrations of alliin, allicin, and S-allyl cysteine (SAC) were evaluated. A major strength of this study is the integration of a traditional pharmacopeial preparation with modern analytical characterization.</p><p><strong>Methods: </strong>Ma'joun Soum was prepared from fresh garlic, clarified cow butter (cow ghee), pasteurized milk, honey, and herbal ingredients according to the traditional pharmacopeial formulation. After preparation, samples were aged under three different conditions: room temperature (25°C), in a stability chamber (40°C), and under traditional underground aging conditions (33 - 36°C). The concentrations of alliin, allicin, and S-allyl cysteine (SAC) were quantified over time using high-performance liquid chromatography (HPLC), and sulfur-containing compounds were characterized using headspace gas chromatography-mass spectrometry (GC-MS).</p><p><strong>Results: </strong>Storage temperature and aging duration significantly influenced the chemical profile of Ma'joun Soum. Alliin exhibited a transient increase during the early stage of storage, followed by a gradual decline, whereas SAC progressively accumulated under all storage conditions. GC-MS analysis demonstrated a reduction in volatile sulfur-containing compounds during aging, while HPLC revealed compositional changes in selected water-soluble organosulfur compounds. These findings indicate that aging promotes complex chemical transformations within the formulation rather than simply preserving the original sulfur constituents.</p><p><strong>Conclusions: </strong>Short-term aging of Ma'joun Soum promotes the conversion of garlic-derived organosulfur compounds toward a composition enriched in stable, water-soluble sulfur metabolites, particularly SAC. Although the present study does not directly compare this formulation with conventional aged garlic extract (AGE), the findings suggest that controlled short-term aging may be a promising strategy for accelerating sulfur compound transformation in traditional garlic formulations.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e167972"},"PeriodicalIF":1.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008509","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":"Dual Targeting of CXCR4 and CXCL12 by 1,2,4-Triazole Derivatives: A Computational Approach Against Lung Cancer Metastasis.","authors":"Yeni Yeni, Fransiska Kurniawan, Benny Permana, Daryono Hadi Tjahjono","doi":"10.5812/ijpr-171955","DOIUrl":"10.5812/ijpr-171955","url":null,"abstract":"<p><strong>Background: </strong>Migration of lung cancer cells to distant sites is largely mediated by the CXCR4/CXCL12 axis. Meanwhile, 1,2,4-triazole derivatives have shown antiproliferative activity in lung cancer and have been reported to inhibit metastasis in pancreatic and breast cancer.</p><p><strong>Objectives: </strong>This study aimed to screen 1,2,4-triazole derivatives with high potential to target the CXCR4/CXCL12 axis associated with lung cancer metastasis using multiple computational methods.</p><p><strong>Methods: </strong>A total of 79 1,2,4-triazole derivatives were screened using ligand-based pharmacophore modeling (LigandScout Essential 4.4.9) and molecular docking (AutoDock 4.2.6). Molecular dynamics (MD) simulations were then performed using GROMACS 2021.4 to further characterize protein-ligand interactions. Finally, compound safety, biological behavior, and drug-development feasibility were evaluated using toxicity prediction (ProTox 3.0) and pharmacokinetic and drug-likeness assessments (pkCSM).</p><p><strong>Results: </strong>Sixteen derivatives (D41-D51 and D53-D57) matched the CXCR4 and CXCL12 pharmacophore models. The CXCR4 model (model 8) comprised two hydrophobic features, one aromatic ring, and one hydrogen bond donor, whereas the CXCL12 model (model 3) included one hydrophobic feature, two aromatic rings, and three hydrogen bond acceptors. Docking studies against CXCR4 and CXCL12 indicated that D54 and D57 had more favorable predicted docking scores than mavorixafor (a CXCR4 inhibitor) and LIT-927 (a CXCL12 inhibitor). These findings were supported by MD simulations, as indicated by stable root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), hydrogen bond (H-bond) occupancy, and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) results. Toxicity and pharmacokinetic predictions suggested that D54 and D57 had both favorable properties and potential liabilities.</p><p><strong>Conclusions: </strong>Compounds D54 and D57 were computationally prioritized as promising 1,2,4-triazole derivatives targeting the CXCR4/CXCL12 axis for further investigation in lung cancer metastasis. However, their predicted toxicity, pharmacokinetic, and drug-likeness profiles revealed several limitations that warrant further optimization and experimental validation.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e171955"},"PeriodicalIF":1.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008395","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":"The Effectiveness of a Topical Turmeric-Based Formulation on Contact Dermatitis: A Randomized, Double-Blind, Controlled Trial.","authors":"Shabnam Khatami, Seyede Nargess Sadati Lamardi, Roya Najafi-Vosough, Azadeh Mizani, Laila Shirbeigi, Alireza Abbassian","doi":"10.5812/ijpr-172121","DOIUrl":"10.5812/ijpr-172121","url":null,"abstract":"<p><strong>Background: </strong>Contact dermatitis (CD) affects approximately 15% of adults worldwide, and commonly used treatments are often associated with adverse effects. Traditional medicine sources, including Persian medicine, offer promising alternatives. Based on the principles of Persian medicine, the formulation investigated in this study combines <i>Curcuma longa</i> L., <i>Lawsonia inermis</i> L., and <i>Aristolochia rotunda</i> L. (CLA) to achieve a synergistic therapeutic effect.</p><p><strong>Objectives: </strong>This study aimed to evaluate the efficacy and safety of a 4-week intervention using CLA cream in patients with mild-to-moderate CD.</p><p><strong>Methods: </strong>A randomized, double-blind, placebo-controlled trial was conducted in 64 participants who were assigned to apply either CLA cream or the base cream. Assessments included demographic characteristics, the Dermatology Life Quality Index (DLQI), the Three-Item Severity Score (TIS), and skin parameters, including transepidermal water loss (TEWL), stratum corneum hydration, skin pH, and sebum production. Statistical analyses were performed using repeated-measures analysis of variance with least significant difference post hoc tests, Friedman tests, and Wilcoxon tests.</p><p><strong>Results: </strong>The CLA group showed significantly greater decreases in TEWL and TIS scores than the control group (P = 0.004 and P = 0.003, respectively). In the within-group analysis, sebum production increased significantly after the intervention in the CLA group (P = 0.006). <i>Stratum corneum</i> hydration improved significantly in both groups.</p><p><strong>Conclusions: </strong>A 4-week course of CLA cream appears to ameliorate inflammatory symptoms in patients with mild-to-moderate contact dermatitis. Further large-scale, longer-duration trials are warranted to establish the clinical utility of CLA cream as a complementary therapeutic option.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e172121"},"PeriodicalIF":1.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008544","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":"Design, Synthesis, Molecular Dynamics Analysis, and Biological Evaluation of New Urea Derivatives in an Animal Model of Alzheimer Disease.","authors":"Sara Heidarian, Mehrdad Faizi, Mehrdad Alemi, Amir Garmabdari, Noushin Nikray, Mona Khoramjouy, Zahra Hajimahdi, Afshin Zarghi","doi":"10.5812/ijpr-172672","DOIUrl":"10.5812/ijpr-172672","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer disease (AD), first described by Alois Alzheimer more than a century ago, remains a major global health challenge. Glycogen synthase kinase-3β (GSK-3β) plays an important role in AD pathophysiology. Dysregulation of GSK-3β is associated with beta-amyloid accumulation, tau hyperphosphorylation, neurodegeneration, and cognitive impairment.</p><p><strong>Objectives: </strong>This study aimed to design and synthesize 17 arylalkyl urea derivatives as GSK-3β inhibitors and evaluate them in an animal model of AD.</p><p><strong>Methods: </strong>New arylalkyl derivatives were designed on the basis of the pharmacophores of GSK-3β inhibitors. Molecular docking and molecular dynamics simulations were used to evaluate the interactions of the designed compounds within the ATP-binding pocket of GSK-3β. The compounds were then synthesized by reacting substituted anilines with benzyl isocyanate, and their structures were confirmed by infrared spectroscopy, nuclear magnetic resonance spectroscopy, and liquid chromatography-mass spectrometry. The radial arm water maze was used to assess the effects of a selected compound on learning and memory deficits in an intracerebroventricular streptozotocin-induced rat model of sporadic Alzheimer-like disease.</p><p><strong>Results: </strong>Structure-activity relationship analysis indicated that variations in the R₁ and R₂ substituents played a crucial role in modulating GSK-3β inhibitory activity. Docking studies demonstrated that all novel derivatives fit well within the active site, with Val135 and Lys85 contributing prominently to ligand stabilization. On the basis of the docking results, compound 3b was selected for behavioural testing. Compound 3b significantly ameliorated spatial learning and memory deficits in a rat model of AD.</p><p><strong>Conclusions: </strong>Compound 3b emerged as a promising lead in this series, combining favorable GSK-3β binding properties with robust cognition-enhancing effects in vivo. These findings may inform therapeutic design, clinical translation, and strategic development in the evolving field of AD drug discovery.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e172672"},"PeriodicalIF":1.7,"publicationDate":"2026-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012310","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":"Binding of Epimedium Flavonoids to Human Serum Albumin: Insights from Spectroscopic and Molecular Docking Studies.","authors":"Na Wang, Yuwei Wang, Yang Yang, Lele Dong, Yi Zhao","doi":"10.5812/ijpr-172525","DOIUrl":"10.5812/ijpr-172525","url":null,"abstract":"<p><strong>Background: </strong>Epimedin A (EA), epimedin B (EB), and epimedin C (EC), major bioactive flavonoids in Epimedium Herba, have diverse pharmacological activities; however, their interactions with human serum albumin (HSA) remain unclear.</p><p><strong>Objectives: </strong>This study aimed to investigate the binding mechanisms of EA, EB, and EC to HSA.</p><p><strong>Methods: </strong>Multispectroscopic techniques, including UV-vis, fluorescence, and synchronous fluorescence spectroscopy, as well as molecular docking and dynamics simulations, were employed under simulated physiological conditions. <i>Fluorescence spectra</i> were recorded at 298, 303, and 310 K, and molecular docking was performed with HSA (PDB ID: 1BKE).</p><p><strong>Results: </strong>All three flavonoids quenched the intrinsic fluorescence of HSA via static quenching, forming 1:1 complexes with binding constants greater than 10⁴ L·mol^-1 (EB > EA > EC at 298 K). Thermodynamic analysis indicated spontaneous binding driven by hydrogen bonds and van der Waals forces. Synchronous fluorescence showed no significant microenvironmental changes around Trp and Tyr residues. Molecular docking and dynamics simulations suggested ligand-dependent differences in the preferred binding regions of HSA.</p><p><strong>Conclusions: </strong>These findings provide preliminary in vitro evidence for the binding of epimedin flavonoids to HSA and may inform future pharmacokinetic investigations.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e172525"},"PeriodicalIF":1.7,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008336","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":"Serine Protease Inhibitor 1 (SERPINE1) Regulates Epithelial-Mesenchymal Transition Gene Expression to Promote Migration and Invasion in Hepatocellular Carcinoma.","authors":"Run Bao, Zhaoxia Luo, Liao Gang, Wen Huang, Sheng Wu, Fangmin Xu","doi":"10.5812/ijpr-163908","DOIUrl":"10.5812/ijpr-163908","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is characterized by a high capacity for invasion and metastasis. Epithelial-mesenchymal transition (EMT) is a key mechanism that promotes tumor migration and invasion. However, the role of serine protease inhibitor 1 (SERPINE1) as a regulatory factor that may enhance tumor progression by directly modulating EMT-related gene expression in HCC has not been fully elucidated.</p><p><strong>Objectives: </strong>To investigate the role of SERPINE1 in regulating EMT-related gene expression and its effects on tumor invasion and migration in hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>A comprehensive experimental approach integrating in vitro cell models, animal experiments, and clinical sample analyses was employed. qPCR, immunohistochemistry, and Western blotting were performed to determine SERPINE1 expression in HCC cell lines and tissues. SERPINE1 expression was modulated by RNA interference and overexpression, and the effects on HCC cell migration and invasion, as well as the expression of EMT markers, were evaluated.</p><p><strong>Results: </strong>SERPINE1 expression was approximately 3.2-fold and 2.8-fold higher in metastatic liver cancer cells and cancer tissues, respectively (P < 0.01). SERPINE1 expression was significantly negatively correlated with E-cadherin (r = -0.72) and positively correlated with vimentin (r = 0.65). After SERPINE1 knockdown, E-cadherin protein expression increased 2.1-fold, whereas N-cadherin and vimentin expression decreased by 68% and 55%, respectively; cell migration and invasion decreased by 62% and 57%, respectively (P < 0.01). Conversely, SERPINE1 overexpression reduced E-cadherin to 0.4-fold of the control level, whereas N-cadherin and vimentin increased 2.3-fold and 2.0-fold, respectively, and migration and invasion increased 1.9-fold and 2.1-fold, respectively. In the in vivo orthotopic lung metastasis model, SERPINE1 knockdown reduced the number of lung metastatic foci from 4.8 ± 1.1 to 1.5 ± 0.6 (P < 0.01), and the incidence of metastasis decreased from 83.3% to 33.3%. Mechanistic studies revealed that, after SERPINE1 knockdown, the p-AKT/AKT and p-ERK/ERK ratios decreased by 64% and 57%, respectively, and the EMT transcription factors Snail and Slug were downregulated; PI3K agonists partially reversed the inhibition of the EMT phenotype. These results suggest that SERPINE1 activates the PI3K/AKT and MAPK signaling pathways, upregulates EMT-related gene expression, and thereby promotes liver cancer cell migration, invasion, and lung metastasis.</p><p><strong>Conclusions: </strong>SERPINE1 facilitates the migration and invasion of HCC cells by modulating EMT-related gene expression. SERPINE1 is upregulated in liver cancer tissues and may contribute to liver cancer progression.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e163908"},"PeriodicalIF":1.7,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008476","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":"ALDH1A3 Inhibition by <i>Prosopis farcta</i> Phytochemicals: A Computational Exploration of a Potential Antidiabetic Mechanism.","authors":"Nilufar Torabi, Gholamreza Taheripak, Nabaa Najjar, Mohammad Amin Nooraniyan Esfehani, Najme Sadat Hoseini, Ghahraman Abedi-Firouzjaei","doi":"10.5812/ijpr-169211","DOIUrl":"10.5812/ijpr-169211","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus is a chronic condition caused by insufficient insulin secretion or impaired insulin action. Traditionally, pancreatic β-cell loss has been attributed to hyperglycemia-induced apoptosis. However, more recent evidence indicates that β-cells can also undergo dedifferentiation, a process in which they lose their specialized identity and revert to a precursor-like state. ALDH1A3 has been reported as a marker associated with dedifferentiated β-cells in diabetes, making it a potential molecular target for studies of β-cell identity and their redifferentiation.</p><p><strong>Objectives: </strong>This study aimed to evaluate the potential interactions between phytochemicals in <i>Prosopis farcta</i> root extract and ALDH1A3 using an in silico workflow that included molecular docking, molecular dynamics simulations, and Molecular Mechanics Generalized Born Surface Area (MM-GBSA) analysis.</p><p><strong>Methods: </strong>This in silico study evaluated phytochemicals reported in the root extract of <i>Prosopis farcta</i>. The three-dimensional structures of the phytochemicals were downloaded from the PubChem database in SDF format. Molecular docking and molecular dynamics simulations were performed using PyRx and GROMACS, respectively. MM-GBSA analysis was performed using gmx_MMPBSA.</p><p><strong>Results: </strong>Docking analysis suggested that several <i>Prosopis farcta</i> phytochemicals could interact with functionally relevant regions of ALDH1A3, including the retinal- and NAD-binding regions. Among the evaluated compounds, luteolin 7-O-glucoside and luteolin 3'-glucoside exhibited favorable docking scores and stable interaction profiles in subsequent MD and MM-GBSA analyses. These findings suggest that these compounds may form energetically favorable interactions with ALDH1A3.</p><p><strong>Conclusions: </strong>Among the evaluated <i>Prosopis farcta</i> phytochemicals, luteolin 7-O-glucoside and luteolin 3'-glucoside emerged as the most promising computational candidates for further ALDH1A3-focused studies. These findings provide an initial basis for investigating whether interaction with ALDH1A3 may represent a potential mechanism contributing to the reported antidiabetic effects of <i>Prosopis farcta</i> extract and its possible relevance to β-cell dysfunction in diabetes. However, experimental validation is essential to confirm ALDH1A3 inhibition, its effects on β-cell redifferentiation, and antidiabetic potential.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169211"},"PeriodicalIF":1.7,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008281","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}