Iranian Journal of Pharmaceutical Research最新文献

{"title":"Effect of Lemon Inhalation Aromatherapy on Postoperative Pain, Nausea and Vomiting, Delirium, and Inflammatory Markers After Coronary Artery Bypass Grafting: A Triple-Blind Randomized Trial.","authors":"Siavash Sangi, Seyed Mohammadreza Amouzegar Zavareh, Hedayat Sahraei, Mojtaba Sepandi, Alireza Moradi","doi":"10.5812/ijpr-168770","DOIUrl":"10.5812/ijpr-168770","url":null,"abstract":"<p><strong>Background: </strong>Complementary and integrative medicine has gained increasing attention as a safe adjunct for improving postoperative outcomes, particularly in cardiac surgery where pain, postoperative nausea and vomiting (PONV), and delirium remain common and debilitating complications.</p><p><strong>Objectives: </strong>This randomized clinical trial aimed to investigate the effect of lemon inhalation aromatherapy on postoperative pain, PONV, delirium, and inflammatory markers in patients undergoing coronary artery bypass grafting (CABG) surgery.</p><p><strong>Methods: </strong>In this triple-blind, parallel-group randomized controlled trial, 104 adult patients scheduled for elective CABG surgery were randomly allocated to either lemon aromatherapy or an odorless placebo. Aromatherapy began the evening before surgery, was administered every two hours until anesthesia induction, and resumed continuously during mechanical ventilation and for 72 hours after extubation. Pain and PONV were assessed every 6 hours across eight postoperative shifts using a 0 - 10 Numeric Rating Scale. Delirium was evaluated at 24, 48, and 72 hours using the intensive care delirium screening checklist (ICDSC). Inflammatory markers [C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR)] were measured at baseline and 72 hours. Data were entered after double-checking into SPSS version 26. Continuous variables were tested for normality using the Shapiro-Wilk test; normally distributed variables were compared using independent <i>t</i>-tests, and non-normal variables with the Mann-Whitney U test. Categorical variables were analyzed using chi-square or Fisher's exact test. All analyses were two-tailed with a significance level of P < 0.05.</p><p><strong>Results: </strong>Of the 104 randomized patients, 103 completed the study (one patient in the intervention group was withdrawn due to postoperative cerebrovascular insult). The two groups were well-balanced at baseline with respect to demographic and clinical characteristics. Pain scores were significantly lower in the intervention group at all eight postoperative shifts (P < 0.001). Postoperative nausea and vomiting severity was significantly reduced across all shifts (P < 0.001), with fewer vomiting episodes and lower need for rescue antiemetic medications. The incidence of delirium was significantly lower in the intervention group at 24 hours (11.8% vs. 28.8%), 48 hours (15.7% vs. 34.6%), and 72 hours (7.8% vs. 23.1%) (all P < 0.05). Significant improvements were also observed in multiple ICDSC subscales, particularly inattention, disorientation, sleep-wake disturbances, and inappropriate speech/mood. At 72 hours, both CRP and NLR levels were significantly lower in the aromatherapy group, suggesting attenuation of the postoperative inflammatory response. No aromatherapy-related adverse events were observed.</p><p><strong>Conclusions: </strong>Lemon inhalation aromatherapy was effective in significant","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e168770"},"PeriodicalIF":1.7,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306254","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":"Comparative Study on the Effects of Ginseng and Green Tea Extracts on Selected Lipid Metabolism Markers in Adipocyte.","authors":"Mandana Salehi, Kahin Shahanipour, Ramesh Monajemi, Parisa Mohamadynejad","doi":"10.5812/ijpr-162445","DOIUrl":"10.5812/ijpr-162445","url":null,"abstract":"<p><strong>Background: </strong>Dietary patterns are effective in obesity treatment. This has led to more investigations on its mechanisms in combating obesity.</p><p><strong>Objectives: </strong>This study investigated the effects of ginseng and green tea extracts (GTE) on selected markers of lipid metabolism and the expression of some related genes in adipocytes.</p><p><strong>Methods: </strong>After a one-month period of consuming a high fatty content diet, a total of 42 male Wistar rats were assigned to seven groups randomly. The rats were then subjected to an eight-week treatment where they were administered different dosages of GTE and ginseng extract (GE) through oral administration. Then, some serologic parameters pertaining to lipid metabolism were analyzed in the treated rats. Furthermore, alterations in the expression levels of select genes, bone morphogenetic protein 7 (BMP7), hormone-sensitive lipase (HSL), and leptin, implicated in lipid metabolism, were quantified within the adipose tissue of the rats utilizing the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) methodology. Ultimately, the chemical composition of the extracts was analyzed by high performance liquid chromatography (HPLC).</p><p><strong>Results: </strong>The findings indicated that the utilization of the extracts had a notable impact on the reduction of body weight. There was a noteworthy enhancement of high-density lipoprotein levels across all study groups, as indicated by a statistically significant increase at a confidence level of 95%. The efficacy of the administered extracts was observed in a significant upregulation in BMP7 and HSL gene expression. Conversely, there was a notable reduction in leptin expression, which reached statistical significance at a confidence level of 95%. HPLC results detected 9 ginsenosides in the GE, among which Rb1 (100 mAU) was present in the largest amount, and 9 alkaloids in the GTE, among which epicatechin (EC) (380 mAU) and caffeine (320 mAU) were present in the largest amount.</p><p><strong>Conclusions: </strong>The present study holds the potential to offer novel insights regarding the mechanism through which GE and GTE exert their anti-obesity effects.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e162445"},"PeriodicalIF":1.7,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13180287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972681","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":"KIM-1 as an Early Diagnostic Biomarker of Cisplatin-Induced Acute Kidney Injury.","authors":"Ai-Hui Jin, Yan-Jie Zheng, Chen-Long Xu, Li Zhou, Hao Wang, Wen-Juan Wang","doi":"10.5812/ijpr-164432","DOIUrl":"10.5812/ijpr-164432","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) is a frequent complication of cisplatin chemotherapy, largely due to its toxic accumulation in renal proximal tubules. Current biomarkers show limited sensitivity in early detection, underscoring the need for more specific indicators. Kidney Injury Molecule-1 (KIM-1), upregulated in damaged tubular cells, shows promise as an early and accurate AKI biomarker.</p><p><strong>Objectives: </strong>This multimodal study integrates bioinformatic analyses, in vitro experiments, and a systematic review with meta-analysis to comprehensively evaluate KIM-1 expression, function, and early diagnostic performance.</p><p><strong>Methods: </strong>We analyzed single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq) data to assess HAVCR1 expression and co-regulated genes in kidney tissue and cisplatin-treated HK-2 cells. Protein interactions were mapped using STRING and Cytoscape. In vitro assays, including quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and Cell Counting Kit-8 (CCK-8), were conducted on cisplatin-treated HK-2 cells. For the systematic review and meta-analysis, a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided search was conducted in PubMed, Scopus, Web of Science, Cochrane Library, and CNKI to identify studies evaluating urinary KIM-1 for early (≤ 24 h) detection of cisplatin-induced AKI. Study eligibility was based on clinical AKI defined by serum creatinine criteria, early KIM-1 measurement, and extractable 2 × 2 diagnostic data. Risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool, and pooled estimates were generated using a bivariate model.</p><p><strong>Results: </strong>Single-cell and bulk RNA-seq analyses revealed that HAVCR1 (KIM-1) is specifically expressed in proximal tubular cells and is upregulated following cisplatin-induced injury. Gene enrichment and protein interaction analyses confirmed its association with epithelial transport and injury response pathways. In vitro, cisplatin treatment led to dose-dependent increases in KIM-1 mRNA and protein levels. Meta-analysis showed that urinary KIM-1 has acceptable diagnostic accuracy (AUC = 0.76; 95% CI: 0.65 - 0.86) as an early biomarker for cisplatin-induced AKI.</p><p><strong>Conclusions: </strong>KIM-1 is a proximal tubule-specific, injury-responsive biomarker that is upregulated early during cisplatin-induced kidney damage. Integrative bioinformatic and experimental analyses underscore its potential for early AKI detection, and the meta-analysis further supports its emerging clinical utility.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e164432"},"PeriodicalIF":1.7,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972447","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":"Paclitaxel- and Sirolimus-Coated Drug-Coated Balloons versus Drug-Eluting Stents in Acute Myocardial Infarction: A Comprehensive Systematic Review and Meta-Analysis.","authors":"Zhengmin Zhang, Gang Yu, Rong Guo","doi":"10.5812/ijpr-164739","DOIUrl":"10.5812/ijpr-164739","url":null,"abstract":"<p><strong>Context: </strong>Acute myocardial infarction (AMI) requires rapid yet durable coronary reperfusion. Drug-eluting stents (DES) are the standard for percutaneous coronary intervention (PCI) but pose long-term challenges such as late stent thrombosis and extended dual antiplatelet therapy (DAPT). Drug-coated balloons (DCBs), using paclitaxel or newer sirolimus formulations, deliver antiproliferative therapy without leaving a permanent scaffold, offering a potentially safer, stent-free option.</p><p><strong>Objectives: </strong>To evaluate the efficacy and safety of DCBs versus DES in AMI, with emphasis on drug platform (paclitaxel vs. sirolimus) and specific outcomes.</p><p><strong>Methods: </strong>This systematic review and meta-analysis followed PRISMA 2020 guidelines. Databases including PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from inception through 15 January 2025, according to a prospectively archived protocol on the Open Science Framework. Thirty-four eligible studies (14 randomized controlled trials (RTCs), 20 observational cohorts) comprising 19,642 participants and 2,313 major adverse cardiovascular events (MACE) were analyzed. Dichotomous outcomes were synthesized as pooled risk ratios (RRs) with 95% confidence intervals (CIs) using a random-effects (DerSimonian-Laird) model; heterogeneity was quantified by I², τ², and H² statistics.</p><p><strong>Results: </strong>Drug-coated balloons were associated with a 15% relative reduction in MACE compared with DES (RR = 0.85, 95% CI: 0.73 - 0.99, I² = 63.2%). Rates of myocardial infarction (MI) (RR = 0.93, 95% CI: 0.78 - 1.11), target lesion revascularization (TLR) (RR = 0.88, 95% CI: 0.71 - 1.07), and cardiovascular mortality (RR = 0.97, 95% CI: 0.81 - 1.16) were comparable between groups. Late stent thrombosis was significantly lower with DCBs (RR = 0.64, 95% CI: 0.42 - 0.97). Most pooled evidence involved paclitaxel-coated balloons, while sirolimus-coated DCB data, though directionally consistent, remain limited by smaller sample size and shorter follow-up.</p><p><strong>Conclusions: </strong>This meta-analysis suggests that DCBs represent a feasible, stent-free PCI strategy in AMI, providing comparable safety and efficacy to DES with a potential advantage in reducing late thrombosis. Device selection should be guided by lesion complexity, bleeding risk, and DAPT tolerance. Further large-scale, head-to-head randomized trials, particularly involving sirolimus-coated DCBs, are warranted to validate these findings.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e164739"},"PeriodicalIF":1.7,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13180300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972616","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 TYK2/JAK1 Inhibition by Brepocitinib Reprograms Synoviocyte Pathobiology: Mechanistic Insights Into Targeted Therapy for Rheumatoid Arthritis.","authors":"Umar Saeed, Zahra Zahid Piracha, Andromeda M Nauli, Surya M Nauli","doi":"10.5812/ijpr-166019","DOIUrl":"10.5812/ijpr-166019","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial hyperplasia, persistent inflammation, and joint destruction. Targeted inhibition of intracellular signaling pathways, such as JAK-STAT, has improved RA treatment outcomes, though safety and selectivity remain as concerns. Brepocitinib, a dual TYK2/JAK1 inhibitor, has shown clinical efficacy in the management of autoimmune diseases, yet its mechanistic impact on synoviocytes remains underexplored.</p><p><strong>Objectives: </strong>To investigate the molecular and functional effects of brepocitinib on MH7A and RA-FLS synoviocytes, a key effector cell type in RA pathogenesis.</p><p><strong>Methods: </strong>MH7A and RA-FLS cells were treated with brepocitinib (0.5 µM, 1 µM, and 5 µM) for 24 hours. Cell viability was assessed. Western blotting was used to examine phosphorylation of TYK2, JAK1, STAT1/3, and apoptotic markers (BAX, BCL-2, caspase-3). Quantitative PCR and ELISA were performed to evaluate mRNA and protein levels, respectively, of IL-6, TNF-α, and IFN-γ. Wound healing assays measured synoviocyte migration.</p><p><strong>Results: </strong>Brepocitinib maintained ≥ 85% cell viability across all doses, compared with ~20% viability in doxorubicin-treated controls. At 5 µM, phosphorylation of JAK1 and STAT3 was suppressed by > 80%, while TYK2 and STAT1 inhibition reached ~70%. IL-6 and TNF-α transcripts were reduced by > 80% and IFN-γ by ~70%, with corresponding decreases in secreted cytokines (IL-6: 100 pg/mL to 20 pg/mL; TNF-α: 150 pg/mL to 15 pg/mL; IFN-γ: 41 pg/mL to 11 pg/mL). Brepocitinib shifted the BAX/BCL-2 ratio fourfold in favor of apoptosis and increased cleaved caspase-3 levels to ~80% of maximal response. Functionally, it reduced wound closure from ~75% in controls to ~20% at 5 µM, confirming potent inhibition of synoviocyte migration.</p><p><strong>Conclusions: </strong>Brepocitinib exerts multi-faceted effects on RA synoviocytes by simultaneously inhibiting inflammatory signaling, suppressing cytokine expression, restoring apoptotic sensitivity, and reducing migratory potential. These findings provide mechanistic support for brepocitinib as a targeted therapeutic agent in RA.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e166019"},"PeriodicalIF":1.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306262","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":"Tehranolide Attenuates Lipid Accumulation in Steatotic HepG2 Cells via cAMP/AMPK/SIRT1-Mediated Autophagy Activation.","authors":"Shima Lorestani, Shahla Mohammad Ganji, Shokoofe Noori","doi":"10.5812/ijpr-168037","DOIUrl":"10.5812/ijpr-168037","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic condition marked by abnormal lipid buildup within hepatocytes, leading to inflammation and liver injury. Hepatic lipid accumulation can be driven by multiple factors, including high glucose, free fatty acids, and lipotoxic stress. Autophagy, which may be influenced by metabolic regulators such as cyclic adenosine monophosphate (cAMP), AMP-activated protein kinase (AMPK), and sirtuin 1 (SIRT1), is suggested to contribute to the maintenance of hepatic lipid homeostasis. Tehranolide, a sesquiterpene lactone derived from &lt;i&gt;Artemisia diffusa&lt;/i&gt; and structurally related to artemisinin, is believed to have hepatoprotective effects similar to artemisinin. This work is the first to assess the impact of tehranolide on lipid accumulation with emphasis on autophagy/AMPK/SIRT1 signaling in steatotic human hepatoma-derived cells (HepG2).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This investigation was undertaken to evaluate the potential of tehranolide to reduce lipid accumulation in a high-glucose-induced steatotic hepatocyte model, potentially involving autophagy-related signaling pathways such as cAMP, AMPK, and SIRT1.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A high-glucose-induced steatotic model was established in HepG2 cells. After determining the effective concentration of tehranolide by means of the MTT assay, lipid-loaded cells received treatment with tehranolide. The content of intracellular triglycerides (TGs) was determined via Oil Red O staining and commercial kits. The expression of lipid metabolism-related genes [fatty acid synthase (FASN), sterol regulatory element-binding protein 1c (SREBP-1c), and SIRT1] and autophagy markers [light chain 3 (LC3), beclin-1] was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), while protein levels of LC3-I, LC3-II, AMPK, and phosphorylated AMP-activated protein kinase (p-AMPK) were evaluated by Western blotting. Intracellular cAMP levels, lactate dehydrogenase (LDH) release, and inflammatory cytokines were also quantified using commercial kits.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Tehranolide significantly decreased intracellular TG levels, downregulated lipogenic genes (FASN, SREBP-1c), and upregulated the lipolytic gene SIRT1. It increased the expression of autophagy-related markers (beclin-1 and LC3-II). Furthermore, tehranolide increased intracellular cAMP and AMPK phosphorylation, while inhibition of SIRT1 or blockade of autophagy attenuated these effects. In addition, tehranolide reduced glucose-induced cytotoxicity and suppressed pro-inflammatory cytokine production in HepG2 cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Tehranolide attenuates lipid accumulation and inflammatory responses in high-glucose-induced steatotic HepG2 cells, potentially involving autophagy-related processes, which may be linked to cAMP, AMPK, and SIRT1. These findings suggest that tehranolide may represent ","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e168037"},"PeriodicalIF":1.7,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561948","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":"MEK1/2 Inhibitor (U0126) and PI3K Inhibitor (LY294002) Suppress Herpes Simplex Virus Type 1 Replication by Targeting MAPK/ERK1/2 and PI3K/AKT Signaling Pathways: Implications for Oral Health and Translational Control of Orolabial HSV-1 Infection.","authors":"Wei Meng, Zahra Zahid Piracha, Umar Saeed, Dilber Uzun Ozsahin, Ilker Ozsahin, Yongwei Tao, Zhanping Ren","doi":"10.5812/ijpr-164639","DOIUrl":"10.5812/ijpr-164639","url":null,"abstract":"<p><strong>Background: </strong>Current antivirals for orolabial Herpes simplex virus type 1 (HSV-1) often provide incomplete suppression and limited reactivation control, sustaining recurrent oral lesions and inflammation that compromise oral health. HSV-1 subverts host signaling networks to enhance its replication and trigger inflammation. Among these, the extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways are hijacked to facilitate viral gene expression and cell survival.</p><p><strong>Objectives: </strong>In this study, we employed U0126 [a mitogen-activated protein kinase 1/2 (MEK1/2) inhibitor] and LY294002 [a phosphatidylinositol 3-kinase (PI3K) inhibitor] as targeted pharmacological tools to intercept HSV-1's exploitation of host keratinocyte signaling.</p><p><strong>Methods: </strong>Human HaCaT keratinocytes were infected with HSV-1 and treated with U0126 or LY294002. Western blotting was used to assess phosphorylation of ERK1/2 and activation of protein kinase B (AKT). MTT assays were performed to evaluate cell viability. Real-time PCR was utilized to quantify viral transcripts (ICP0, ICP4, gB, and gC) and inflammatory cytokines [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)]. Confocal microscopy was employed to visualize the intracellular distribution of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), phosphorylated activation of protein kinase B (p-AKT), and HSV-1 glycoprotein D (gD). Viral titers were determined using plaque assays.</p><p><strong>Results: </strong>The HSV-1 infection induced a time-dependent increase in phosphorylation of ERK1/2 and AKT, with p-ERK1/2 peaking at 12 h and p-AKT increasing 2.5-fold by 24 h. Cell viability declined from 100% at baseline to 45% at 24-hours post-infection (hpi). Treatment with U0126 and LY294002 reduced p-ERK1/2 and p-AKT levels to 25% and 30% of infected controls, respectively, restoring viability to 82 - 86%. Both inhibitors markedly suppressed viral gene expression (ICP0, ICP4, gB, gC down by 60 - 80%) and inflammatory cytokines (IL-6 and TNF-α reduced by > 50%). Plaque assays showed a strong decline in infectious titers - from 175 plaques per well in untreated infection to 60 and 45 plaques after U0126 and LY294002, respectively. Confocal imaging further revealed diminished nuclear accumulation of p-ERK1/2 and p-AKT, indicating disruption of post-entry signaling critical for viral replication.</p><p><strong>Conclusions: </strong>Targeting host signaling bottlenecks with U0126 and LY294002 offers a dual-pronged antiviral strategy against HSV-1 by dismantling the ERK/AKT axis critical for replication and inflammatory amplification. These findings position MEK1/2 and PI3K as promising therapeutic nodes for managing cutaneous HSV-1 infections. This host-directed dual-pathway inhibition may therefore help reduce recurrent orolabial HSV-1 lesions.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e164639"},"PeriodicalIF":1.7,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306110","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":"Experts back call to include pregnant women in clinical trials","authors":"","doi":"10.1211/pj.2026.1.404658","DOIUrl":"https://doi.org/10.1211/pj.2026.1.404658","url":null,"abstract":"Pregnant and breastfeeding women should be routinely included in clinical research, where safe and appropriate, the British Pharmacological Society (BPS) has said. In a position statement published on 18 March 2026, the BPS warned that longstanding gaps in evidence are leaving healthcare professionals and patients without the information needed to make safe and informed decisions […]","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147883542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin-Loaded Avocado Oil Nanoemulsion Reverses High-fat and High-carbohydrate Diet-Induced Testicular Dysfunction: Role of Oxidative Stress and NPY Signaling in a Randomized Trial.","authors":"Hamidreza Mazangi, Negar Panahi, Saeed Hesaraki, Shahabeddin Safi","doi":"10.5812/ijpr-165025","DOIUrl":"10.5812/ijpr-165025","url":null,"abstract":"<p><strong>Background: </strong>High-fat and high-carbohydrate diets (HF) can negatively affect male reproductive function, impairing spermatogenesis and testosterone production. Quercetin (Qu) may mitigate testicular damage, but its effectiveness is limited by poor bioavailability. Avocado oil (AO) improves blood lipid levels and enhances the absorption of fat-soluble nutrients.</p><p><strong>Objectives: </strong>We explore the impact of AO combined with quercetin on weight gain, dyslipidemia, hormonal dysregulation, testicular oxidative stress, and NPY signaling, all induced by a HF diet, to highlight testicular dysfunction and metabolic disorders.</p><p><strong>Methods: </strong>A nanoemulsion of avocado oil containing quercetin (NAOQu) was developed as an oil-in-water (O/W) nanoemulsion, utilizing the hydrophilic-lipophilic balance (HLB) value and conducting stability assessments, followed by characterization (DLS, Zeta potential, and TEM). Thirty rats were fed an HF diet for 8 weeks and treated with either Qu, a nanoemulsion of avocado oil (NAO), or NAOQu. Body weight was determined, and serum was analyzed for triglycerides (TG), cholesterol, HDL, and testosterone levels. Testicular homogenates were assessed for malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) activity, and cholesterol. Hypothalamic NPY mRNA expression was quantified using qPCR.</p><p><strong>Results: </strong>The NAOQu (1% Qu, 1:1 avocado: Coconut oil) exhibited a stable, spherical morphology with a particle size of 286.7 nm, a zeta potential of -25.8 mV, and enhanced physical stability. The NAOQu significantly reduced body weight, improved lipid profiles (lowering TG and cholesterol while increasing HDL), and restored testosterone levels by 85% compared to high-fat diet (HFD) controls and reduced testicular MDA by 62% while increasing GSH and SOD activities by 2.3-fold and 1.8-fold, respectively. Molecular analyses revealed decreased testicular cholesterol levels and downregulated NPY mRNA expression, indicating reduced metabolic stress.</p><p><strong>Conclusions: </strong>The combined NAOQu formulation showed greater protective effects than Qu or AO alone, suggesting a synergistic effect. These findings highlight the potential of avocado oil-based nanoemulsion as an effective delivery system for Qu, offering a novel therapeutic strategy to counteract HF-induced male reproductive dysfunction and metabolic disease.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e165025"},"PeriodicalIF":1.7,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226818","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 Role of GRP78/ATF6/IRE1 and Caspase-12 Signaling Pathways in the Protective Effects of n-Hexane Oil Extract of Black Soldier Flies' Larvae (<i>Hermetia illucens</i>) Against Aflatoxin-Induced Hepatotoxicity in Rats.","authors":"Fateme Heidari, Tahereh Zarei Taher, Yalda Arast","doi":"10.5812/ijpr-167846","DOIUrl":"10.5812/ijpr-167846","url":null,"abstract":"<p><strong>Background: </strong>Global contamination of agricultural products with aflatoxin (AF) is one of the most important concerns in the field of food safety and quality. Aflatoxin, when entering the food chain, can cause oxidative stress and hepatotoxicity. Black soldier fly larvae (BSFL) are an environmentally friendly insect whose extract is rich in valuable bioactive compounds with antioxidant properties.</p><p><strong>Objectives: </strong>This study aimed to investigate the protective effect of the n-hexane extract of BSFL on oxidative stress, inflammation, and histopathological changes caused by Aflatoxin B1 (AFB1)-induced hepatotoxicity in rats.</p><p><strong>Methods: </strong>Thirty-five male Wistar rats with a weight range of 200 to 250 g were randomly divided into 5 equal groups including Control, AFB1 (75 μg/kg), BSFL (360 mg/kg), BSFL 180 mg/kg+AFB1, and BSFL 360 mg/kg+AFB1. At the end of the treatment on the twenty-eighth day, the animals were euthanized and samples were taken for liver enzymes, oxidative stress, inflammation, endoplasmic reticulum (ER) stresses, apoptosis marker, histopathology, and expression of ER stress-related proteins analyses. Data were analyzed by one-way ANOVA followed by Tukey's post-hoc test, with P < 0.05 considered statistically significant.</p><p><strong>Results: </strong>According to the results of the study, AFB1 administration significantly increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) (P < 0.001) and also decreased the levels of superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT) compared to the control group (P < 0.001). These biochemical and inflammatory abnormalities caused by AFB1 were confirmed by histopathological observations of liver tissue. Administration of BSFL extract (at the higher dose of 360 mg/kg) resulted in significant reversal of biochemical, inflammatory, and hepatic markers and modulated GRP78/ATF6/IRE1 signaling in AF-poisoned rats. Our histological results showed that BSFL extract (360 mg/kg) could reduce steatosis, cellular swelling, and lobular inflammation induced after AF exposure.</p><p><strong>Conclusions: </strong>The results of this study indicate that BSFL extract, as a valuable bioactive substance with antioxidant properties, may attenuate biochemical indices, oxidative stress, and inflammation caused by AF-induced hepatotoxicity.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"24 1","pages":"e167846"},"PeriodicalIF":1.7,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12915366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226874","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}