Iranian Journal of Pharmaceutical Research最新文献

{"title":"External Knowledge Search and Innovation Performance in Iranian Biopharmaceutical Firms: The Mediating Role of Knowledge Integration Capability.","authors":"Fatemeh Babaei, Nazila Yousefi, Mohammad Peikanpour","doi":"10.5812/ijpr-164658","DOIUrl":"10.5812/ijpr-164658","url":null,"abstract":"<p><strong>Background: </strong>In the biopharmaceutical sector, characterized by rapid technological change and intense market competition, external knowledge search (EKS) has become a strategic necessity to overcome the limitations of closed innovation. However, while EKS is widely studied in developed economies, its underlying mechanisms remain underexplored in emerging biopharmaceutical sectors.</p><p><strong>Objectives: </strong>This cross-sectional study examines how EKS affects innovation performance (IP) in Iranian biopharmaceutical firms, testing the mediating role of knowledge integration capability (KIC) and the moderating effect of R&D intensity, while controlling for firm size and age.</p><p><strong>Methods: </strong>Data were collected using a validated questionnaire completed by 92 senior executives (CEOs, R&D, and Business Development managers) from 44 Iranian biopharmaceutical companies. The model was analyzed using partial least squares structural equation modeling (PLS-SEM) in SmartPLS.</p><p><strong>Results: </strong>EKS significantly enhances both IP (β = 0.462, P < 0.001) and KIC (β = 0.239, P < 0.003). KIC positively influences IP (β = 0.437, P < 0.001) and partially mediates the EKS-IP relationship (indirect effect β = 0.104, P = 0.02). R&D intensity showed no significant moderating effect (β = 0.198, P = 0.10). The model explains 40.5% of IP variance (R² = 0.405). Firm size (β = 0.009, P = 0.924) and age (β = 0.030, P = 0.792) had no significant effects.</p><p><strong>Conclusions: </strong>The impact of EKS on IP depends more on a firm's KIC than on its R&D intensity. This study advances open innovation theory by clarifying how external knowledge is effectively translated into innovation outcomes within an emerging biopharmaceutical context.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e164658"},"PeriodicalIF":1.7,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561971","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":"Pharmacological SIRT2 Inhibition by AGK2 Attenuates Hapten-Induced Keratinocyte Inflammation via NF-κB/NLRP3 Suppression and Nrf2 Reactivation.","authors":"Xianhua Qiao, Xinglong Yu, Juanjuan Gao, Chong Lv, Fang Cheng","doi":"10.5812/ijpr-169951","DOIUrl":"10.5812/ijpr-169951","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Allergic contact dermatitis (ACD) is initiated by hapten-induced keratinocyte oxidative stress and inflammatory signaling, commonly involving NF-κB activation, NLRP3 inflammasome priming-associated signaling, and inadequate Nrf2-dependent antioxidant responses. Identification of druggable upstream regulators that integrate these pathways could support host-directed pharmacological strategies for dermatitis-like inflammation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate whether pharmacological inhibition of SIRT2 using AGK2 mitigates hapten-triggered inflammatory-oxidative stress signaling in human keratinocytes and to define the associated molecular mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Human Ker-CT keratinocytes were cultured alone or in transwell co-culture with CCD-1064Sk dermal fibroblasts and stimulated with 2,4-dinitrochlorobenzene (DNCB); nickel sulfate served as a comparator sensitizer. Cells were treated with the selective SIRT2 inhibitor AGK2, and target engagement was verified by acetyl-α-tubulin accumulation. Outcomes included viability (MTT), ROS generation (DCFDA), cytokine expression/secretion (qPCR/ELISA), and pathway signaling (Western blotting, immunofluorescence, nuclear-cytoplasmic fractionation), focusing on NF-κB (p65/IκBα), NLRP3 priming-associated readouts (NLRP3 expression and IL-1 family cytokine output), and Nrf2 localization with downstream antioxidant enzymes (HO-1, SOD). To strengthen specificity beyond pharmacological inhibition, SIRT2 involvement was genetically validated using siRNA-mediated knockdown (siSIRT2) in Ker-CT cells. In addition, AGK2-alone control groups (without DNCB) were included across major readouts to assess baseline effects on NF-κB, ROS, and Nrf2 signaling, and Keap1 expression was examined as mechanistic support for altered Nrf2 regulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;DNCB produced a reproducible sub-toxic keratinocyte stress phenotype characterized by increased ROS, activation of NF-κB signaling with IκBα degradation and p65 nuclear translocation, upregulation of NLRP3 expression with elevated IL-1β/IL-18 secretion consistent with enhanced inflammasome-associated inflammatory responses, and impaired Nrf2 nuclear accumulation with reduced antioxidant enzyme expression. AGK2-mediated SIRT2 inhibition significantly attenuated NF-κB activation and reduced pro-inflammatory cytokine outputs, while reducing NLRP3 priming-associated responses and lowering IL-1β/IL-18 secretion. In parallel, AGK2 restored Nrf2 nuclear translocation and enhanced expression of HO-1 and SOD, resulting in partial normalization of intracellular redox balance. Importantly, siSIRT2 phenocopied AGK2 effects by reducing DNCB-induced NF-κB activation, ROS accumulation, and restoring nuclear Nrf2 enrichment. AGK2 alone did not significantly alter basal NF-κB signaling, ROS levels, or Nrf2 nuclear localization, supporting that AGK2 effects were stimulus-dependent rather than intrinsic","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169951"},"PeriodicalIF":1.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13187688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987573","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 Mesna Co-administration in the Management of Acute Pancreatitis: A Pilot Randomized Clinical Trial.","authors":"Amir Sadeghi, Mohammad-Yousef Fazel, Mohammad Abbasinazari, Laleh Mahmoudi, Seyed-Mehregan Sadatsafavi, Parvaneh Mohammadi","doi":"10.5812/ijpr-168523","DOIUrl":"10.5812/ijpr-168523","url":null,"abstract":"<p><strong>Background: </strong>The use of antioxidants has been shown to mitigate the symptoms of acute pancreatitis (AP) and improve associated biomarkers.</p><p><strong>Objectives: </strong>In light of the antioxidant properties of mesna, this pilot study was undertaken to determine whether the addition of mesna to standard treatment for AP offers superior outcomes compared with standard treatment alone.</p><p><strong>Methods: </strong>In a randomized open-label pilot trial, patients diagnosed with AP were enrolled in the study. Intravenous mesna at a dose of 400 mg/day was administered for 7 days. Clinical indicators, including the Harmless Acute Pancreatitis Score (HAPS), amylase, lipase, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and malondialdehyde (MDA), were measured at baseline and after the 7-day treatment period.</p><p><strong>Results: </strong>Although MDA levels significantly decreased in the group receiving mesna combined with standard therapy compared with the group receiving standard therapy alone after 7 days (P = 0.01), no significant differences were observed between the 2 groups in terms of HAPS, amylase, lipase, CRP, or ESR.</p><p><strong>Conclusions: </strong>These findings suggest that the addition of mesna at a daily dose of 400 mg did not influence the overall outcome of AP after 7 days. Further large-scale studies with varying doses and durations of mesna administration are recommended.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e168523"},"PeriodicalIF":1.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13180390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971883","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 Methylacrylylated Hyaluronic Acid Hydrogels in Promoting Skin Wound Healing.","authors":"Chunfang Zheng, Waifung Mai, Liqi Zou, Lianying Li, Bingwei Sun","doi":"10.5812/ijpr-169881","DOIUrl":"10.5812/ijpr-169881","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hyaluronic acid, as a natural extracellular matrix component, possesses excellent biocompatibility and moisturizing properties, and demonstrates unique advantages in wound repair.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To explore the role of hyaluronic acid methacryloyl (HAMA) hydrogels in skin wound healing and analyze the characteristics of the local microenvironment of wounds.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Mice divided into a control group (n = 6) and a HAMA group (n = 6) at random were used to create a model of total cortical resection. 100μL of HAMA hydrogel was applied to the wound surface in the HAMA group, while 100 μL of lithium phenyl-2,4,6-trimethylbenzoyl hypophosphonate (LAP) was applied to the wound surface in the control group. Both were irradiated with an ultraviolet lamp for 20 seconds, and on days 0, 3, 7, 10, and 14, the residual wounds were measured. The effect of the HAMA hydrogel on wound healing was analyzed by measuring the remaining wound area and performing hematoxylin-eosin (H&E) staining. The cellular characteristic spectrum of the local skin of the wound on the 14th day was analyzed via single-cell sequencing technology, and the degree of type I and type III collagen expression, F4/80, CD206 and CD86 in the local wound were detected via immunohistofluorescence technology. The mRNA expression levels of Arg1, Nos2, Itgam and Itgb2 in the RAW264.7 mouse macrophage line coincubated with the HAMA hydrogel for 24 hours were detected by RT-qPCR. Cluster analysis of fibroblasts and macrophages in the local skin of the wounds on the 14th day in mice was conducted via the Seurat software package, and the communication status between fibroblasts and macrophages was analyzed via the CellChat software package.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The HAMA group's skin wounds healed considerably more quickly than the control group's did. While the wounds in the control group had not yet fully healed, those in the HAMA group had by the fourteenth day. Single-cell sequencing analysis revealed that the proportion of fibroblast subsets with high expression of Col3a1 in the HAMA group (90.2%) was greater than that in the control group (79.8%), whereas the proportion of fibroblast subsets with high expression of Colla1 (5.7%) was lower than that in the control group (15.9%). The results of the immunofluorescence analysis confirmed that the local type III collagen level in the wounds of the HAMA group was greater than that in the wounds of the control group (P = 0.035), whereas the type I collagen level was lower than that in the wounds of the control group (P = 0.044). There was no significant difference in the proportion of local macrophages on the wound surface between the HAMA group mice and the control group mice. However, both the single-cell sequencing analysis results and the in vitro treatment of Raw264.7 macrophages with the HAMA hydrogel revealed increased expression of Arg1 (P &lt; 0.001) and decreased ex","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169881"},"PeriodicalIF":1.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972463","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":"Four Steroidal Saponins Isolated from the Aerial Parts of <i>Allium jesdianum</i> Exhibit Antibiofilm Effects Against Colistin-Resistant Clinical Strains, with an In Silico Study.","authors":"Saeid Eslami, Behzad Zolfaghari, Masoud Sadeghi Dinani, Arezoo Mirzaee, Hajar Sirous, Mustafa Ghanadian","doi":"10.5812/ijpr-169955","DOIUrl":"10.5812/ijpr-169955","url":null,"abstract":"<p><strong>Background: </strong>Global health security is critically threatened by multidrug-resistant Gram-negative bacteria, which frequently overexpress efflux pumps to expel antibiotics, rendering last-resort drugs like colistin ineffective and diminishing treatment options.</p><p><strong>Methods: </strong>This study investigated the antibacterial and antibiofilm potential of four steroidal saponins isolated from the aerial parts of <i>Allium jesdianum</i> Boiss. & Buhse against colistin-resistant strains of <i>Klebsiella pneumoniae</i>, <i>Escherichia coli</i>, <i>Acinetobacter baumannii</i>, and <i>Pseudomonas aeruginosa</i>. Compounds were extracted, purified using modern chromatographic techniques, and structurally characterized via NMR and mass spectrometry as known saponins, including aginoside and F-gitonin derivatives.</p><p><strong>Results: </strong>Four steroidal-type saponins were isolated. Bioactivity assays revealed that compounds 1 - 3 exhibited minimum inhibitory concentrations (MICs) of 4 mg/mL against colistin-resistant pathogens: <i>Klebsiella pneumoniae</i>, <i>Escherichia coli</i>, and <i>Acinetobacter baumannii</i>, though no bactericidal activity was observed via agar diffusion. Notably, compound 3 demonstrated the strongest antibiofilm activity, achieving up to 75% inhibition at 4 mg/mL. Quantitative real-time PCR analysis showed that all compounds upregulated efflux pump genes (adeB, acrA, blaKPC, oprL), which limit their antibacterial activity. Molecular docking studies further supported the interaction of compound 3 with the adeB efflux pump, indicating strong binding affinity via hydrogen bonding and hydrophobic interactions.</p><p><strong>Conclusions: </strong>These findings highlight the saponin profile in aerial parts of edible plant <i>A. jesdianum</i> as well as their modest antibacterial activity, but with potential as adjuvants in combating biofilm formation.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169955"},"PeriodicalIF":1.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13187685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987547","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":"Cross-Sectional Study on Blood Coagulation Profile and Platelet Indices in Normal Term Pregnancy and Term pregnancy with Preeclampsia","authors":"Suchana Sinha, Raju Gopal Saha, Pradip Sarkar, Rajib Pal, Jhantu Kumar Saha","doi":"10.25258/ijcpr.18.4.38","DOIUrl":"https://doi.org/10.25258/ijcpr.18.4.38","url":null,"abstract":"Background: Preeclampsia is a significant hypertensive disorder of pregnancy associated with endothelial dysfunction, altered coagulation, and platelet abnormalities. These haemostatic changes increase the risk of maternal and fetal complications. Evaluating coagulation parameters and platelet indices can aid in early detection, risk stratification, and management of preeclampsia. Methods: A cross-sectional observational study was conducted among 180 term pregnant women (90 normotensive and 90 preeclamptic) at Burdwan Medical College. Participants were selected using simple random sampling. Clinical evaluation and laboratory investigations including BT (Bleeding Time), CT (Clotting Time), PT (Prothrombin Time), APTT (Activated Partial Thromboplastin Time), platelet count, MPV (Mean Platelet Volume), PDW (Platelet Distribution Width), and D-dimer levels were performed. Data were analyzed using SPSS with appropriate statistical tests, considering p ≤ 0.05 as significant. Results: Preeclamptic women showed significantly higher systolic and diastolic blood pressure (p &lt; 0.001). Coagulation parameters-BT, CT, PT, and APTT-were significantly prolonged in the preeclamptic group (p &lt; 0.001). Platelet count was significantly reduced (1.17 ± 0.6 vs. 1.438 ± 0.36 lakh/mm³; p = 0.033), while MPV and PDW were significantly elevated (p &lt; 0.05), indicating increased platelet activation and turnover. D-dimer levels were also significantly higher in preeclamptic women (p &lt; 0.001), reflecting enhanced fibrinolytic activity. Conclusion: Preeclampsia is associated with significant alterations in coagulation profile and platelet indices, indicating a hypercoagulable yet consumption-driven state. Routine monitoring of these parameters can facilitate early diagnosis, assess disease severity, and prevent complications such as DIC and HELLP syndrome, thereby improving maternal and fetal outcomes.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"18 04","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147888082","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":"Photodynamic Therapy Combined with Gemcitabine for Prostate Cancer Using Nanoprobe for in-vivo CEST Imaging.","authors":"Qibo Fu, Qian Liu, Xianyou Zeng, Laoji Wang, Jierou Yan, Ding He, Jilin Xie","doi":"10.5812/ijpr-169821","DOIUrl":"10.5812/ijpr-169821","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Current clinical treatment is confronted with challenges such as low drug delivery efficiency, lagging efficacy evaluation, and a high tumor recurrence rate. However, chemical exchange saturation transfer (CEST) imaging, with its molecular specificity and non-invasive monitoring advantages, provides a new path for real-time tracking of the metabolokinetics of nanoprobes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;Drug-loaded nanoprobes that self-assembled and had CEST activation imaging capabilities were created, and there in vivo and in vitro CEST activation imaging efficacy and the value of photodynamic sensitization for pyroptosis treatment of prostate cancer cells were evaluated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A self-assembly strategy was adopted to construct a nanoprobe (GC) coloaded with gemcitabine (Gem) and the photosensitizer chlorin e6 (Ce6), and a scanning electron microscope was used. Scanning electron microscope (SEM), dynamic light scattering (DLS), etc., were used to characterize the in vitro CEST activation imaging efficacy of the nanoprobe, and the pH, concentration-, and time-dependent drug release were observed. GC was combined with 2',7'-dichlorodihydrogen fluorescein diacetate ester (2',7'-dichlorodihydrofluorescein diacetate) after laser treatment of prostate cancer cells in mice. The generation of reactive oxygen species (ROS) was detected with a DCFH-DA probe. By using ELISA, the amounts of inflammatory factors such as interleukin-1β (IL-1β) and IL-18 were determined, and calreticulin was detected via immunofluorescence. CRT and high mobility group box 1 protein (HMGB1) were used to evaluate pyroptosis-mediated immunogenic cell death (ICD) effects. A mouse prostate cancer tumor model was constructed to observe the CEST-specific activation effect of the GC nanoprobes in vivo, and its tumor volume was measured, together with the detection of inflammatory substances and ICD markers, in order to assess its pyroptosis-based anticancer activity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Scanning electron microscope and DLS analyses revealed that the GC nanoprobes had a uniform spherical-like structure. The release of the drug Gem by this drug-loaded nanoprobe under acidic conditions at pH 5.0 was as high as 80%, which was significantly greater than that at pH 7.4 (P = 0.003). DCFH-DA fluorescence staining indicated that photosensitizing pyroptosis mediated by nanoprobes could generate a large amount of ROS. The detection of pyroptosis-related factors revealed that the levels of IL-1β and IL-18 significantly increased (all P &lt; 0.05), whereas the fluorescence of the ICD marker CRT increased and that of HMGB1 decreased. The results of in vivo experiments indicated that the CEST signal at the tumor site was significantly enhanced and reached its peak 4 hours after tail vein injection of the GC nanoprobes. In addition, the results of antitumor treatment in vivo revealed that, compared with those in the control group tr","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169821"},"PeriodicalIF":1.7,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972445","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":"Baicalein Protects H9c2 Cardiomyoblasts Against LPS-Induced Inflammatory Injury by Modulating the NF-κB/NLRP3 Inflammasome Pathway and Mitochondrial ROS.","authors":"Yi Lu, Zahra Zahid Piracha, Umar Saeed, Fangjun Luo","doi":"10.5812/ijpr-169689","DOIUrl":"10.5812/ijpr-169689","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Sepsis-related cardiomyopathy is mainly induced by uncontrolled inflammation and mitochondrial oxidative damage triggered by endotoxins, especially those of Gram-negative bacteria. Lipopolysaccharide (LPS), an endotoxin, activates the Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) signaling pathway and the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which further activates caspase-1 to process the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Chronic activation of this signaling pathway is responsible for mitochondrial damage and loss of membrane potential. Baicalein, a flavonoid derived from the herbal plant &lt;i&gt;Scutellaria baicalensis&lt;/i&gt; is well recognized for its anti-inflammatory and antioxidant properties, although its full modulation of the NF-κB/NLRP3 mitochondrial signaling pathway is not thoroughly understood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;In this study, we assessed whether baicalein has a protective effect on H9c2 cardiomyoblasts against inflammatory and mitochondrial injury induced by LPS through regulation of inflammatory pathways involving NF-κB, the inflammasome, caspase-1 activity, cytokine expression, and oxidation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;H9c2 cells were pre-exposed to different baicalein concentrations (5 - 20 µM) and, after 1 hour, exposed to 1 µg/mL of LPS. Analysis included cell viability measurements by MTT assay, lactate dehydrogenase (LDH) release, and microscopic evaluation by phase-contrast microscopy. Expression levels of premature Nlrp3, Il1B, Il18, and Casp1 (0 - 4 h) were analyzed by real-time polymerase chain reaction (PCR). Protein levels of inflammasome and NF-κB pathway proteins were evaluated by immunoblot analysis. Activity of caspase-1 and cytokine secretion of IL-1β and IL-18 were evaluated by colorimetry and enzyme-linked immunosorbent assay (ELISA), respectively. Mitochondrial membrane potential (ΔΨm) was evaluated by staining with JC1 dye, and reactive oxygen species (ROS) levels were evaluated by fluorescence with DCFH2DA; N-acetylcysteine (NAC) was used as an antioxidant positive control.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;LPS strongly elevated the transcription of Nlrp3 and Il1b at 2 hours, in addition to enhancing protein expression of NLRP3, activity of caspase-1, and secretion of IL-1β and IL-18. Underlying these pro-inflammatory responses were mitochondrial depolarization, augmented ROS production, diminished cell survival, and cytotoxicity. Prior administration of baicalein mitigated NF-κB activation, diminished priming of the inflammasome response at both transcriptional and protein levels, and decreased caspase-1 activity and secretion of the cytokines. Moreover, baicalein maintained mitochondrial membrane potential and diminished ROS within the cells, comparable to NAC, and improved cellular viability and morphology.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Baicalein confers substantial pr","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169689"},"PeriodicalIF":1.7,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13187689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987545","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":"Folic Acid Ameliorates the Chronic Constriction Injury of Sciatic Nerve -Induced Memory Impairments in Rats.","authors":"Arunachalam Muthuraman, Mohamed Meeran Sheik Davooth, Seema Mehdi, Nallupillai Paramakrishnan, Satbir Kaur, Thiagharajan Venkata Rathina Kumar, Khian Giap Lim, Yamunna Paramaswaran","doi":"10.5812/ijpr-166629","DOIUrl":"10.5812/ijpr-166629","url":null,"abstract":"<p><strong>Background and objective: </strong>The present study investigated the effect of folic acid in a rat model of sciatic nerve injury (SNI)-induced cognitive dysfunction.</p><p><strong>Methods: </strong>In this study, six groups with six male Wistar rats in each group were used. The simple randomization method was adopted for unbiased assignment of animals based on age, sex, and weight variations. Folic acid (10 and 20 mg/kg) and donepezil (1 mg/kg) were administered by the oral (p.o.) route for 10 days. The rats' cognition was assessed by the Morris water maze (MWM) test. The assessment of the learning trial (acquisition) was the escape latency time (ELT), while the assessment of memory retention (retrieval) was the time spent in the target quadrant (TSTQ), which was measured in the MWM test. The brain samples of rats were used to assess biomarkers such as total protein, reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and acetylcholinesterase (AChE) activity. The behavioral data were statistically analyzed by a two-way analysis of variance (ANOVA) test, and biomarkers were analyzed by one-way ANOVA. The 95% confidence level (P < 0.05) was fixed for confirmation of statistical significance.</p><p><strong>Results: </strong>The administration of folic acid statistically (P < 0.05) reduced the SNI-induced elevated ELT and TSTQ levels compared to the sham control group. However, folic acid also prevented the rise in TBARS and AChE activity and the drop in GSH after SNI. The comparable outcomes were statistically (P < 0.05) similar to those of the donepezil-administered group.</p><p><strong>Conclusions: </strong>Folic acid has great potential to be used in treating peripheral nerve injury-associated cognitive dysfunction.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e166629"},"PeriodicalIF":1.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13180334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971839","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":"Antimalarial Activity of Methoxylated Flavonoid Fraction (Cirsimaritin-Dominated) from <i>Artemisia kopetdaghensis</i> in <i>Plasmodium berghei</i>-Infected Mice with in silico Analysis.","authors":"Roya Amirian, Seyed Hossein Hejazi, Naser Ghoddosi, Hamed Fouladseresht, Morteza Sadeghi, Seyed Mahmoud Mousavi, Zeinab Yazdiniapour, Maryam Fattahian, Mustafa Ghanadian","doi":"10.5812/ijpr-167100","DOIUrl":"10.5812/ijpr-167100","url":null,"abstract":"<p><strong>Background: </strong>Building on our previous investigation of the total semipolar extract (SPE) of <i>Artemisia kopetdaghensis</i> in <i>Plasmodium berghei</i>-infected mice, the present study focuses specifically on the methoxylated flavonoid fraction (MFF). Flavonoids are increasingly recognized for their ability to suppress parasite growth and modulate host immunity. To clarify their role, we isolated and characterized the major flavonoid constituents of this plant and evaluated their antimalarial potential, both alone and in combination with chloroquine, in a mouse model.</p><p><strong>Methods: </strong>Aerial parts of <i>A. kopetdaghensis</i> were extracted using a chloroform:acetone (2:1) solvent mixture. The extract was then fractionated by column chromatography. Based primarily on ^1H-NMR spectra, the MFF was selected and further purified by preparative HPLC. Isolated compounds were identified by 1D and 2D NMR and mass spectrometry. In the in vivo antimalarial study, thirty-six infected female Balb/c mice were treated with MFF and evaluated for key parameters. Docking and molecular interaction studies were conducted using AutoDock v4.2.6 software to examine the interactions of constituents with cytokine protein targets: 1D9C [interferon-gamma (IFN-γ)], 1B6C (TGF-β), 1BBN [(interleukin-4 (IL-4)], and 4HR9 (IL-17), separately.</p><p><strong>Results: </strong>Phytochemical analysis of the MFF by HPLC revealed three flavones: 6-methoxytricin (20%), cirsilineol (10%), and cirsimaritin (70%), identified for the first time in <i>A. kopetdaghensis</i>, with cirsimaritin as the dominant constituent. In vivo, MFF treatment significantly reduced parasitemia and enhanced parasite suppression in <i>P. berghei</i>-infected mice. Cytokine profiling demonstrated suppression of TGF-β and IL-4 followed by their recovery, together with marked elevations of IFN-γ and IL-17, indicating balanced modulation between pro-inflammatory and regulatory responses. These immunological findings were corroborated by molecular docking analyses, which confirmed binding interactions of cirsimaritin with cytokine receptor targets, providing mechanistic support for its immunomodulatory activity.</p><p><strong>Conclusions: </strong>This work extends our previous study on the SPE by moving from extract-level observations to constituent-specific insights. By combining phytochemical isolation with in silico receptor interaction analysis, we demonstrate that methoxylated flavonoids, particularly cirsimaritin, are key modulators of host immunity and promising candidates for further development as adjuncts or leads in antimalarial therapy.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e167100"},"PeriodicalIF":1.7,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549060","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}