Iranian Journal of Pharmaceutical Research最新文献

{"title":"Renoprotective Effects of <i>Allium jesdianum</i> Against <i>Cyclophosphamide</i>: Role of Antioxidant Enzymes and Pro-inflammatory Cytokines in a Murine Model.","authors":"Alireza Rezaei, Bahareh Sadat Yousefsani, Ameneh Omidi, Kobra Shirani","doi":"10.5812/ijpr-168361","DOIUrl":"10.5812/ijpr-168361","url":null,"abstract":"<p><strong>Background: </strong>Cyclophosphamide (CP), a widely used chemotherapeutic agent, induces significant nephrotoxicity through oxidative stress and inflammation. <i>Allium jesdianum</i>, a less-studied wild <i>Allium</i> species, has documented antioxidant and anti-inflammatory properties.</p><p><strong>Objectives: </strong>This study aimed to investigate the renoprotective effects of <i>A. jesdianum</i> extract (AJE) against CP-induced kidney injury, focusing on its simultaneous modulation of oxidative and inflammatory pathways.</p><p><strong>Methods: </strong>Mice were randomly divided into four groups: Control, AJE only, CP only, and AJE + CP. Treatments were administered for 14 days. Kidney function, oxidative stress markers, inflammatory cytokines, and histopathological changes were evaluated.</p><p><strong>Results: </strong>CP administration significantly increased serum urea and creatinine levels, enhanced lipid peroxidation, and reduced antioxidant enzyme activities. Histopathological analysis revealed marked renal damage. Pretreatment with AJE significantly attenuated these alterations by restoring renal function markers (P < 0.01), reducing oxidative stress (P < 0.001), and enhancing antioxidant defenses (P < 0.001). Compared with the CP-only group, AJE also significantly reduced levels of pro-inflammatory cytokines (P < 0.001).</p><p><strong>Conclusions: </strong>AJE exerts significant protective effects against CP-induced nephrotoxicity through dual antioxidant and anti-inflammatory mechanisms.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e168361"},"PeriodicalIF":1.7,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549004","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":"Overcoming Liability of Outsidership Under Sanctions: A Capability-Based Framework from Emerging Market Pharmaceuticals.","authors":"Sheida Paknejad, Mahdi Mohammadzadeh","doi":"10.5812/ijpr-169173","DOIUrl":"10.5812/ijpr-169173","url":null,"abstract":"<p><strong>Background: </strong>Sanctions and economic constraints impose substantial barriers to firm internationalization in emerging economies, particularly by exacerbating the liability of outsidership (LOO), defined as the disadvantages associated with exclusion from critical business networks. Despite extensive research on barriers to internationalization, limited attention has been paid to how firms in sanctioned economies leverage organizational capabilities to mitigate LOO at the micro level.</p><p><strong>Objectives: </strong>Drawing on the resource-based view, dynamic capabilities theory, and the Uppsala internationalization model, this study examined how pharmaceutical companies navigate LOO under sanctions through the strategic deployment of organizational capabilities.</p><p><strong>Methods: </strong>A qualitative multiple-case study was conducted in 10 Iranian pharmaceutical companies operating internationally under sanctions. Data were collected through interviews with senior executives and analyzed using thematic analysis.</p><p><strong>Results: </strong>The findings indicated three main interrelated routes through which capabilities mitigate LOO: 1) networking capability (NC) increases absorptive capacity (AC) by establishing trust-based relationships and facilitating knowledge exchange; 2) AC enhances operational capability (OC) by aligning operations with international benchmarks; and 3) NC, AC, and OC jointly reduce LOO by enabling access to alternative networks, strengthening operational legitimacy, and generating a competitive advantage.</p><p><strong>Conclusions: </strong>This study contributes to the internationalization literature by demonstrating how sanctions intensify LOO and necessitate the reconfiguration of firm capabilities. The findings show that dynamic capabilities interact with operational capabilities to support internationalization in constrained environments.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169173"},"PeriodicalIF":1.7,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912031","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":"Exploration of Endophytic Fungal Communities in Three <i>Hypericum</i> Species: Molecular Identification and Evaluation of Antibacterial Activity Against Clinically Relevant Pathogens.","authors":"Fahimeh Nabi, Ahmad Asgharzadeh, Javad Asili, Abolfazl Shakeri","doi":"10.5812/ijpr-167951","DOIUrl":"10.5812/ijpr-167951","url":null,"abstract":"<p><strong>Background: </strong>Endophytic fungi, which inhabit internal plant tissues without causing apparent disease, have emerged as rich sources of bioactive secondary metabolites. <i>Hypericum</i> species are well-known medicinal plants with diverse pharmacological properties; however, the endophytic fungi associated with these species remain largely unexplored.</p><p><strong>Objectives: </strong>This study aimed to isolate and molecularly identify endophytic fungi associated with <i>Hypericum helianthemoides</i>, <i>H. scabrum</i>, and <i>H. perforatum</i>, and to evaluate the antibacterial activity of their extracts against selected pathogenic bacteria.</p><p><strong>Methods: </strong>Endophytic fungi were isolated from the root and stem tissues of three <i>Hypericum</i> species. Molecular identification was performed by amplifying and sequencing the internal transcribed spacer (ITS) and large subunit (LSU) regions of the rRNA gene. The antibacterial activity of the fungal extracts was assessed by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against <i>Staphylococcus aureus</i>, <i>S. epidermidis</i>, <i>Bacillus subtilis</i>, <i>Pseudomonas aeruginosa</i>, and <i>Escherichia coli</i>.</p><p><strong>Results: </strong>A total of 20 fungal isolates were obtained, mainly belonging to the phylum Ascomycota, with one isolate (Absidia sp.) belonging to Zygomycota. <i>H. perforatum</i> harbored the highest number of isolates (40%). Most isolates were newly reported endophytes of <i>Hypericum</i> species. The dominant genera were <i>Fusarium</i> and Alternaria. More than half of the isolates exhibited antibacterial activity, particularly against Gram-positive bacteria, whereas only three species were active against Gram-negative strains. <i>Cladosporium subglobosum</i> demonstrated the most potent antibacterial effect, with MIC and MBC values of 3.125 μg/mL.</p><p><strong>Conclusions: </strong>This study highlights the diversity and antimicrobial potential of endophytic fungi associated with <i>Hypericum</i> species. These findings suggest that such endophytes may represent promising sources of novel bioactive metabolites with potential pharmaceutical applications.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e167951"},"PeriodicalIF":1.7,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549074","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 of Methoxy Amido Xanthate Ligand and Preliminary Rhenium-188 Radiolabeling Studies.","authors":"Ali Ashrfi Goudarzi, Mehdi Salehi Barough, Leila Moghaddam-Banaem, Saeed Kakaei, Fariba Johari Daha","doi":"10.5812/ijpr-171671","DOIUrl":"10.5812/ijpr-171671","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Rhenium-188 (&lt;sup&gt;188&lt;/sup&gt;Re) is a high-energy β&lt;sup&gt;-&lt;/sup&gt;-emitting radionuclide with favorable physical and chemical properties for targeted radionuclide therapy and theranostic applications. In this study, a novel sulfur- and nitrogen-containing chelator, methoxy amido xanthate (MAX), was synthesized and evaluated for efficient radiolabeling with &lt;sup&gt;188&lt;/sup&gt;Re. In a second step, radiolabeling of the alendronate bisphosphonate was assessed for potential theranostic applications in bone metastases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This study aimed to synthesize and characterize the MAX ligand, optimize its radiolabeling with &lt;sup&gt;188&lt;/sup&gt;Re, and evaluate the association between the &lt;sup&gt;188&lt;/sup&gt;Re-MAX complex and alendronate.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The ligand was prepared by reacting chloroacetamide with xanthate derivatives and was characterized using Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. Radiolabeling was performed using generator-eluted sodium perrhenate (&lt;sup&gt;188&lt;/sup&gt;ReO&lt;sub&gt;4&lt;/sub&gt; &lt;sup&gt;-&lt;/sup&gt;) under reducing conditions using stannous chloride and ascorbic acid. Key parameters affecting labeling efficiency, including ligand concentration, pH, reducing agent amount, and the effect of ascorbic acid as a stabilizing agent, were systematically optimized. Radiochemical purity was assessed by instant thin-layer chromatography (ITLC). In the second step, varying amounts of alendronate were added to &lt;sup&gt;188&lt;/sup&gt;Re-MAX under optimal conditions at 100°C for 30 minutes, and radiochemical purity was measured to determine the optimal alendronate amount.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Under optimal conditions (pH 5 - 6), radiochemical yields exceeding 98% were achieved at 100°C (80 - 100 mCi of &lt;sup&gt;188&lt;/sup&gt;Re, 12 mg MAX, 6 mg SnCl&lt;sub&gt;2&lt;/sub&gt;, and 4 mg ascorbic acid) for &lt;sup&gt;188&lt;/sup&gt;Re-MAX. These findings indicate that the MAX ligand forms a stable complex with &lt;sup&gt;188&lt;/sup&gt;Re and represents a promising platform for the development of therapeutic and theranostic radiopharmaceuticals. For &lt;sup&gt;188&lt;/sup&gt;Re-MAX-alendronate, 96% radiochemical purity was achieved by adding 8 mg of alendronate to the mixture at pH 5 - 6.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;A novel MAX ligand was successfully synthesized and radiolabeled with &lt;sup&gt;188&lt;/sup&gt;Re under mild conditions. Alendronate was also labeled using &lt;sup&gt;188&lt;/sup&gt;Re-MAX. High radiochemical yields and purity were achieved by optimizing key labeling parameters. Given the favorable physical characteristics of &lt;sup&gt;188&lt;/sup&gt;Re and the strong chelation observed, the &lt;sup&gt;188&lt;/sup&gt;Re-MAX complex is a viable candidate for the development of therapeutic and theranostic radiopharmaceuticals. The &lt;sup&gt;188&lt;/sup&gt;Re-MAX complex demonstrated favorable radiochemical properties and warrants further biological evaluation, including toxicity, stability, biodistribution, and dosimetric studies, before therapeutic application","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e171671"},"PeriodicalIF":1.7,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549063","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":"Impact of Family Planning Program on Related Drug Consumption in Iran: A Ten-Year Trend Analysis (2014 - 2023).","authors":"Matin Jafari","doi":"10.5812/ijpr-164664","DOIUrl":"10.5812/ijpr-164664","url":null,"abstract":"<p><strong>Background: </strong>Global demographic patterns have shifted substantially over the past century, with declining fertility and accelerated population aging emerging as dominant trends. Iran exemplifies this transition, with an anticipated population peak around 2050 followed by sustained decline. In response, the Family Support and Population Rejuvenation Law (2021) reversed earlier fertility-limiting policies by expanding insurance coverage for infertility therapies while restricting access to subsidized contraceptives and abortifacients, thereby positioning the pharmaceutical sector as a key policy instrument.</p><p><strong>Objectives: </strong>This study aimed to evaluate the impact of the 2021 law on national consumption patterns of reproductive health-related medicines in Iran from 2014 to 2023, including fertility agents, contraceptives, abortifacients, and neonatal treatments.</p><p><strong>Methods: </strong>A retrospective time-series drug-utilization study was conducted using national wholesale data for 52 reproductive medicines, standardized according to the World Health Organization Anatomical Therapeutic Chemical and Defined Daily Dose methodology. Monthly and annual utilization was expressed as defined daily doses per 1000 inhabitants per day. Segmented linear regression and paired t tests were used to compare consumption trends before and after implementation of the law.</p><p><strong>Results: </strong>Of the 52 products examined, 19 dosage forms (37%) across 5 Anatomical Therapeutic Chemical codes showed significant level or slope changes after the law (P < 0.05). Use of infertility treatments, particularly recombinant follitropins, menotropins, and chorionic gonadotropins, increased markedly (+48%, P = 0.01). Despite legal restrictions, use of prostaglandin abortifacients, such as misoprostol and carboprost, also increased (+19%, P = 0.047). Total contraceptive use remained stable; however, market share shifted toward newer low-dose combinations, suggesting substitution rather than reduction. Neonatal surfactant use more than doubled after the law (P < 0.001), raising concerns about increased premature births amid limited prenatal screening.</p><p><strong>Conclusions: </strong>Although the Family Support and Population Rejuvenation Law expanded access to infertility medicines, it did not reduce contraceptive or abortifacient use. Shifts in consumption patterns suggest that regulatory restrictions alone may result in unintended consequences, including clandestine abortion and neonatal complications. A more balanced, evidence-based policy approach is essential to align demographic goals with maternal and newborn health.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e164664"},"PeriodicalIF":1.7,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929884","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":"Hesperetin Attenuates Liver Fibrosis in Mice by Modulating Selected Gut Microbial Populations and SIRT2-Associated Inflammatory Signaling.","authors":"Anzhao Wu, Lingjie Xin, Yuji Liang, Luyan Sun, Qian Liu, Bin Wang, YaPing Li, Yuehong Cui, Umar Saeed, Bo Yang, Zahra Zahid Piracha","doi":"10.5812/ijpr-170978","DOIUrl":"10.5812/ijpr-170978","url":null,"abstract":"<p><strong>Background: </strong>Chronic liver injury progressively induces fibrotic remodeling through persistent inflammatory activity and aberrant extracellular matrix accumulation. Growing evidence indicates that this process involves not only intrahepatic signaling but also gut-liver crosstalk and sirtuin-regulated inflammatory pathways. Hesperetin, a citrus-derived flavanone with reported antioxidant and anti-inflammatory properties, has not been adequately evaluated with respect to microbiota-associated changes and SIRT2-associated signaling during fibrotic liver injury.</p><p><strong>Objectives: </strong>This study investigated whether hesperetin attenuates CCl₄-induced liver fibrosis in mice by modulating selected gut microbial populations and suppressing SIRT2-associated inflammatory signaling pathways.</p><p><strong>Methods: </strong>Male mice were randomly assigned to the vehicle, CCl₄, and CCl₄ + hesperetin groups (n = 5 per group). Liver fibrosis was induced by intraperitoneal administration of CCl₄ twice weekly for six weeks, and hesperetin was administered orally at 100 mg/kg/day. Histological, biochemical, inflammatory, SIRT2-associated, and selected gut microbial endpoints were assessed. The expression levels of α-SMA, TGF-β1, TNF-α, IL-6, and SIRT2 were quantitatively analyzed using quantitative polymerase chain reaction (qPCR), Western blotting, and an enzyme-linked immunosorbent assay (ELISA). Levels of selected gut microflora were measured using targeted qPCR for Firmicutes, <i>Bacteroidetes</i>, Akkermansia, and <i>Escherichia coli</i>.</p><p><strong>Results: </strong>CCl₄ exposure increased collagen deposition, collagen proportionate area (CPA), and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, indicating fibrotic remodeling and hepatocellular injury. Hesperetin treatment significantly decreased collagen deposition and CPA and partially normalized ALT and AST activities compared with CCl₄ treatment alone. Fibrosis biomarkers, including α-SMA and TGF-β1, and inflammatory cytokines, including TNF-α and IL-6, showed significant decreases in expression at both the mRNA and protein levels. Hesperetin reduced CCl₄-associated SIRT2 upregulation and restored acetyl-α-tubulin levels, suggesting attenuation of SIRT2-associated deacetylase activity.</p><p><strong>Conclusions: </strong>These exploratory findings suggest that hesperetin attenuates CCl₄-induced liver fibrosis by reducing collagen accumulation and biochemical liver injury, suppressing inflammatory and fibrogenic signaling, modulating selected gut microbial populations, and regulating SIRT2-associated acetylation signaling.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e170978"},"PeriodicalIF":1.7,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929704","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":"Evaluation of the Protective Effect of n-Hexane Oil Extract of Black Soldier Fly Larvae on Oxidative Stress, Inflammation, and Signaling Pathway Alterations in Acrylamide-Induced Hepatotoxicity in Rats.","authors":"Yalda Arast, Arash Parvaresh, Somaye Behnamipour, Fateme Heidari, Tahereh Zarei Taher, Jalal Pourahmad","doi":"10.5812/ijpr-171556","DOIUrl":"10.5812/ijpr-171556","url":null,"abstract":"<p><strong>Background: </strong>The liver, the body's central organ for metabolism and detoxification, is continually exposed to environmental and dietary toxins such as acrylamide (ACR). ACR is commonly found in roasted and fried foods. Strong scientific evidence indicates that ACR exposure causes serious liver injury. Black soldier fly larvae (BSFL) are an environmentally friendly insect, and their extract is rich in valuable bioactive compounds with antioxidant properties.</p><p><strong>Objectives: </strong>This study aimed to investigate the protective effects of the n-hexane extract of black soldier fly larvae against oxidative stress, inflammation, and histopathological changes associated with ACR-induced hepatotoxicity in rats.</p><p><strong>Methods: </strong>Thirty-five male Wistar rats weighing 200 to 250 g were randomly assigned to five equal groups: control, ACR (20 mg/kg), BSFL (360 mg/kg), BSFL (180 mg/kg) + ACR, and BSFL (360 mg/kg) + ACR. At the end of treatment on the twenty-eighth day, the animals were euthanized, and samples were collected for assessment of liver enzymes, oxidative stress, inflammation, ER stress, apoptosis markers, histopathology, and endoplasmic reticulum stress-related protein expression. Data were analyzed using one-way ANOVA followed by Tukey's post-hoc test, with P < 0.05 considered statistically significant.</p><p><strong>Results: </strong>ACR administration significantly increased AST, ALT, ALP, MDA, and NO levels (P < 0.001), significantly decreased SOD, GSH, GPx, and CAT levels (P < 0.001), and significantly increased TNF-α, IL-1β, and IL-6 levels (P < 0.001) compared with the control group. These ACR-induced biochemical and inflammatory abnormalities were confirmed by histopathological observations of liver tissue. Administration of BSFL extract, at the more potent dose of 360 mg/kg, significantly reversed these biochemical, inflammatory, and hepatic markers. BSFL extract was associated with changes in ER stress-related proteins, apoptosis markers, NF-κB, and MAPK family members, suggesting a potential role in GRP78-mediated ER stress signaling. Histological results showed that BSFL extract (360 mg/kg) reduced steatosis, cellular swelling, and lobular inflammation induced by ACR exposure.</p><p><strong>Conclusions: </strong>The results of this study indicate that BSFL extract, a valuable bioactive substance with antioxidant properties, may attenuate alterations in biochemical indices and reduce oxidative stress and inflammation caused by ACR-induced hepatotoxicity.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e171556"},"PeriodicalIF":1.7,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548995","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":"Hepatic Inflammation and Apoptosis in Socially Isolated Rats: Effects of Vortioxetine Treatment.","authors":"Neziha Senem Arı, Merve Akkuş, Hatice Solak, Raviye Özen Koca, Işık Solak Görmüş","doi":"10.5812/ijpr-170887","DOIUrl":"10.5812/ijpr-170887","url":null,"abstract":"<p><strong>Background: </strong>Depression and chronic psychosocial stress can induce systemic inflammation and oxidative stress that may extend beyond the central nervous system to peripheral organs such as the liver. Social isolation is a widely used rodent model in depression research; however, its hepatic consequences and the potential protective effects of antidepressant treatment remain incompletely characterized.</p><p><strong>Objectives: </strong>This study aimed to investigate whether social isolation induces hepatic inflammation and apoptosis in rats and to evaluate the effects of vortioxetine treatment on these hepatic alterations.</p><p><strong>Methods: </strong>Forty male Wistar albino rats were randomly allocated into four groups (n = 10/group): Control (C), Social Isolation (SI), Vortioxetine (V), and Social Isolation + Vortioxetine (SI+V). Social isolation was maintained for four weeks. Vortioxetine (10 mg/kg/day, intraperitoneally) or vehicle (dimethyl sulfoxide, 1 mL/kg) was administered from days 17 to 31. Liver tissues were examined histopathologically using hematoxylin-eosin and Masson's trichrome staining. Apoptosis was assessed using a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and caspase-3 immunoreactivity. Immunohistochemical analyses were performed for tumor necrosis factor-alpha, nuclear factor-kappa B p65, and cytokeratin-18. Hepatic interleukin-6 levels were quantified by enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>The SI group exhibited marked sinusoidal dilatation, erythrocyte extravasation, hepatocellular ballooning, and inflammatory infiltration, accompanied by increased tumor necrosis factor-alpha, nuclear factor-kappa B p65, and caspase-3 immunoreactivity; increased terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity; and elevated hepatic interleukin-6 levels (P < 0.001). Vortioxetine treatment in isolated rats attenuated these inflammatory and apoptotic responses, resulting in lower histopathological damage scores and better cytokeratin-18 preservation than in the SI group. Masson's trichrome staining showed no significant collagen accumulation among groups (P > 0.05).</p><p><strong>Conclusions: </strong>Social isolation was associated with increased hepatic inflammation and apoptosis, as demonstrated by histopathological, immunohistochemical, and biochemical findings. Vortioxetine treatment was associated with partial attenuation of these alterations. These findings are limited to the measured endpoints and do not establish direct functional effects.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e170887"},"PeriodicalIF":1.7,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591764","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":"Preparation and Evaluation of Zn₂(BDC)₂(DABCO)-β-CD MOF as a Dual-Drug Delivery Nanocomposite Containing Tetracycline and Indomethacin for Skin Wound Healing in BALB/c Mice.","authors":"Farya Mirzaei, Negar Motakef Kazemi, Naser Mohamadpour Dounighi, Mostafa Saffari, Sepideh Arbabi Bidgoli","doi":"10.5812/ijpr-167924","DOIUrl":"10.5812/ijpr-167924","url":null,"abstract":"<p><strong>Background: </strong>Skin wounds complicated by infection and inflammation represent a major clinical challenge and require effective delivery systems that combine antimicrobial and anti-inflammatory agents to promote healing. Nanobased systems, such as metal-organic frameworks (MOFs), are promising platforms for dual-drug delivery because of their high porosity, tunable structure, and biocompatibility.</p><p><strong>Objectives: </strong>This study aimed to synthesize a Zn₂(BDC)₂(DABCO)-β-cyclodextrin MOF nanocomposite using a hydrothermal method and to load indomethacin and tetracycline to develop a dual-drug delivery system that enhances the efficiency and therapeutic efficacy of topical treatment for skin wound healing.</p><p><strong>Methods: </strong>The morphology of the nanocomposite was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Zeta potential was measured using a Zetasizer; the crystalline structure was evaluated by X-ray diffraction (XRD); the physicochemical structure was assessed by Fourier transform infrared (FTIR) spectroscopy; and structural porosity before and after drug loading was analyzed by Brunauer-Emmett-Teller (BET) analysis. The system was then evaluated for in vitro cytotoxicity using the MTT assay, cytokine levels in blood samples from treated mice, and in vivo efficacy in mice, compared with the corresponding pure drugs.</p><p><strong>Results: </strong>The synthesized MOF exhibited high crystallinity. The average particle size was 277 nm for the blank nanocomposite and 545 nm for the drug-loaded nanocomposite, with a zeta potential of -2.6 mV. The drug-loading efficiency in phosphate-buffered saline (PBS; pH 7.4) was 28%, with biphasic release comprising an initial burst followed by sustained release over 144 hours. The BET surface area decreased after drug loading. In vitro studies showed that the drug-loaded nanocomposite was noncytotoxic to L929 fibroblast cells at all tested concentrations. The loaded MOF nanocomposite group showed significantly accelerated wound closure (97.5% on day 6) compared with all other groups (P < 0.05). Cytokine assays in mouse blood samples showed increased interleukin 10 (IL-10) and decreased interferon gamma (IFN-γ) in the group treated with the loaded nanocomposite compared with the control group.</p><p><strong>Conclusions: </strong>The Zn₂(BDC)₂(DABCO)-β-CD nanocomposite containing tetracycline and indomethacin exhibited noncytotoxic behavior, enhanced wound-healing efficacy, and sustained drug release under physiological conditions. These findings highlight its potential as a promising topical drug delivery system.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e167924"},"PeriodicalIF":1.7,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549058","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":"Hepatoprotective Effects of Ethyl Acetate Extract of <i>Lygodium microphyllum</i> Leaves.","authors":"Hadi Kuncoro, Erna Muliana, Putri Anggreini, Angga Cipta Narsa, Zulhaerana Bahar, Vina Maulidya, Nurul Annisa","doi":"10.5812/ijpr-171722","DOIUrl":"10.5812/ijpr-171722","url":null,"abstract":"<p><strong>Background: </strong><i>Lygodium microphyllum</i> is traditionally used in Chinese medicine as a decoction to treat hepatitis.</p><p><strong>Objectives: </strong>This study evaluated the in vivo hepatoprotective efficacy and optimal dose of the ethyl acetate extract of <i>L. microphyllum</i> leaves (EALM) against paracetamol-induced liver injury.</p><p><strong>Methods: </strong>A pilot experiment was conducted in 24 male Wistar rats divided into six groups: a normal control group, a paracetamol control group (3 g/kg body weight [BW]), and three EALM groups (200, 400, and 600 mg/kg BW). EALM was administered orally for 14 days, and paracetamol was administered once on day 8. The evaluated parameters included body weight, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and liver histopathology. Paracetamol intoxication caused significant weight loss and increased AST and ALT levels (P < 0.0001).</p><p><strong>Results: </strong>All EALM doses significantly attenuated paracetamol-induced enzyme elevations. Histopathological analysis revealed severe injury, including pyknosis, in the paracetamol group, whereas EALM-treated livers maintained near-normal morphology. Among the tested doses, 200 mg/kg BW showed the most pronounced protective effect.</p><p><strong>Conclusions: </strong>These findings indicate that EALM has significant hepatoprotective activity against paracetamol-induced hepatotoxicity.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e171722"},"PeriodicalIF":1.7,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549041","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}