Iranian Journal of Pharmaceutical Research最新文献

{"title":"<i>Dendrobium officinale</i> Polysaccharide Promotes Infected Wound Healing Through SIRT1-Regulated HMGB1-K29 Deacetylation and NF-κB Inhibition.","authors":"Yutong Wu, Mohd Hasmizam Razali, Wentao Wu","doi":"10.5812/ijpr-169909","DOIUrl":"10.5812/ijpr-169909","url":null,"abstract":"<p><strong>Background: </strong>Two major challenges frequently encountered during wound healing are excessive inflammatory responses and bacterial infection. <i>Dendrobium officinale</i> polysaccharide (DOP), a major bioactive constituent of <i>Dendrobium officinale</i>, has shown potential for promoting infected wound healing and tissue repair.</p><p><strong>Objectives: </strong>This study evaluated the therapeutic efficacy of DOP in an infected murine wound model, with a specific focus on the role of the SIRT1/HMGB1/NF-κB signaling axis.</p><p><strong>Methods: </strong>Mouse full-thickness skin defect models were established, and animals were divided into four cohorts: control, infected model, DOP-treated, and DOP plus the SIRT1-specific inhibitor EX527. All groups except the control group were inoculated with <i>Staphylococcus aureus</i>. The primary endpoint was wound closure, quantified as the remaining wound surface area on day 14. Secondary outcomes included body weight changes, histopathological injury scores, inflammatory cytokine protein secretion and mRNA transcript levels, SIRT1 expression, HMGB1 subcellular localization, IκBα degradation, and NF-κB p65 phosphorylation.</p><p><strong>Results: </strong>For the primary endpoint, animals receiving DOP had markedly smaller unclosed wound areas on postoperative day 14 than untreated infected animals. Secondary analyses showed that DOP improved body weight recovery and reduced inflammatory cytokine secretion and corresponding mRNA transcript levels. Mechanistically, DOP increased SIRT1 protein levels, promoted HMGB1 deacetylation at the K29 residue with consequent nuclear sequestration, and suppressed IκBα proteolysis and NF-κB p65 phosphorylation. These protective effects were reversed by the SIRT1 inhibitor EX527.</p><p><strong>Conclusions: </strong>By activating SIRT1, DOP promotes K29 deacetylation of HMGB1 and retains this alarmin in the nucleus. The resulting suppression of NF-κB reduces inflammatory injury and counteracts the adverse effects of bacterial infection on wound repair. These findings provide an experimental basis for the potential application of DOP in the management of infected wounds.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169909"},"PeriodicalIF":1.7,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591815","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":"Investigating the Anti-inflammatory Mechanism of <i>Alpinia purpurata</i> (Vieill.) K. Schum. Rhizome Extract: Metabolite Profiling, Network Pharmacology, in vitro Safety, and in vivo Validation.","authors":"Kiki Mulkiya Yuliawati, Fahriza Salsabilla Yuniar, Ellin Febrina, Gofarana Wilar, Raden Maya Febriyanti, Deshanda Kurniawan Prayoga, Faisal Kuswandani, Sri Adi Sumiwi, Supat Jiranusornkul, Jutti Levita","doi":"10.5812/ijpr-169725","DOIUrl":"10.5812/ijpr-169725","url":null,"abstract":"<p><strong>Background: </strong><i>Alpinia purpurata</i> has shown promising effects in alleviating inflammatory conditions; however, its underlying mechanisms require further investigation.</p><p><strong>Objectives: </strong>This study aimed to elucidate the molecular mechanisms underlying the anti-inflammatory activity of <i>A. purpurata</i> rhizome extract (EEAP) and its active metabolites through the TLR4/MyD88 pathway.</p><p><strong>Methods: </strong>The EEAP was analyzed for proximate composition, vitamin C content, total phenolic content (TPC), total flavonoid content (TFC), total monomeric anthocyanin content (TMAC), and metabolite profile, followed by a network pharmacology analysis. Cytotoxicity was evaluated in HEK-293 cells. An in vivo study of carrageenan-induced paw edema in rats was conducted to validate the findings.</p><p><strong>Results: </strong>EEAP contained 42.12% ash, 34.66% moisture, 6.03% protein, 16.60% fat, and 0.59% carbohydrate. The vitamin C content was 941.55 mg/100 g extract, the TPC was 452.9 mg GAE/100 g extract, the TFC was 416.1 mg QUE/100 g extract, and the TMAC was 2770 mg/100 g extract. Functional enrichment analysis identified the TLR4/MyD88 signaling pathway as contributing to IL-23 production. Eight metabolites with anti-inflammatory properties were verified based on their Pa values: glycidyl oleate, 1-stearoylglycerol, alpha-linolenic acid, methyl palmitate, shogaol, 4-methoxybenzaldehyde, ginkgoneolic acid, and curcumene. EEAP was not toxic to HEK-293 cells (IC₅₀= 741.1 μg/mL) compared with quercetin (IC₅₀= 96.73 μg/mL) and cisplatin (IC₅₀= 7.44 μg/mL). EEAP reduced edema volume but did not alter TLR4 or MyD88 expression under the present experimental conditions.</p><p><strong>Conclusions: </strong>EEAP is not toxic to normal cells and exerts an anti-inflammatory effect by reducing edema volume in carrageenan-induced rats; however, it does not alter the TLR4/MyD88 pathway.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169725"},"PeriodicalIF":1.7,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591784","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":"A New Survey about Dual-Acting PARP/COX-2 Inhibitors as Cancer Chemopreventive Agents.","authors":"Mohammad Ismail Mahboubi Rabbani, Ali Aliabadi, Leila Bayat, Mahdokht Jafari, Amir Hossein Bagheri, Sarah Shateri, Rahil Hakimimofrad, Maryam Bayanati, Afshin Zarghi","doi":"10.5812/ijpr-169140","DOIUrl":"10.5812/ijpr-169140","url":null,"abstract":"<p><strong>Context: </strong>Poly(ADP-ribose) polymerase (PARP) is a key enzyme involved in DNA replication. Studies have shown that this enzyme plays a pivotal role in apoptosis and DNA damage repair. Excessive PARP activity, particularly that of PARP-1, may also lead to uncontrolled cellular growth and proliferation, thereby predisposing to tumor development. Similar effects have been observed with the overexpression of cyclooxygenase-2 (COX-2) in cancer development. In this review, our primary objective is to provide a concise and comprehensive structure-activity relationship to guide the design of compounds with dual inhibitory activity against PARP and COX-2. On the basis of this relationship, this review aims to support the development of novel compounds with potent inhibitory activity against PARP-1, as well as the design of dual PARP-1/COX-2 inhibitors.</p><p><strong>Evidence acquisition: </strong>A comprehensive literature search was conducted to identify relevant studies on the design, synthesis, and biological evaluation of novel PARP and PARP-1 inhibitors, as well as dual-acting PARP-1/COX-2 inhibitors. Electronic databases, including Scopus, ScienceDirect, and Google Scholar, were systematically searched. Research articles published in English up to the most recent available date were considered. Studies were screened for relevance, clarity, and compliance with recognized molecular design guidelines. The collected information was analyzed and synthesized to provide an overview of the current state of PARP-1/COX-2 inhibitor synthesis approaches and design trends.</p><p><strong>Results: </strong>Based on the review findings, the use of PARP-1/COX-2 dual inhibitors may be considered a viable therapeutic approach for targeting two interconnected pathways involved in cancer development. Dual-acting agents provide an opportunity to enhance anticancer efficacy and reduce resistance to malignancy. Moreover, preclinical studies have demonstrated synergistic effects. Notably, there are substantial similarities between the SAR of single- and dual-acting PARP-1/COX-2 inhibitors. In addition, polycyclic core structures could be used to guide the design of these compounds. Furthermore, these polycyclic structures may exhibit other important antineoplastic properties, such as inhibition of topoisomerase II (TPO-II).</p><p><strong>Conclusions: </strong>In summary, to provide a more comprehensive review of the design and synthesis of novel chemical compounds as COX-2/PARP-1 dual inhibitors, additional compounds must be developed. Moreover, further clinical development and evaluation are required to improve their pharmacological properties and confirm their safety and efficacy in clinical settings.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169140"},"PeriodicalIF":1.7,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548908","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":"In silico Identification of Natural Compounds as Potential TrkA Inhibitors for Anticancer Drug Development.","authors":"Mujtaba Fadhil, Dhurgham Al-Fahad, Faizul Azam, Asadollah Asadi","doi":"10.5812/ijpr-166946","DOIUrl":"10.5812/ijpr-166946","url":null,"abstract":"<p><strong>Background: </strong>Tropomyosin receptor tyrosine kinase A (TrkA) is essential for cancer cell migration and for stabilizing focal adhesions required for attachment to the extracellular matrix. However, resistance to inhibitors targeting the ATP-binding pocket of the TrkA kinase domain complicates treatment. These inhibitors block ATP binding, which is required for TrkA activation, thereby disrupting downstream signaling pathways involved in cell proliferation and survival in cancers characterized by TrkA overexpression or mutation.</p><p><strong>Objectives: </strong>This study aimed to identify natural compounds as potential TrkA inhibitors for anticancer drug development. The identified compounds exhibited higher binding affinity and greater stability than the control compounds.</p><p><strong>Methods: </strong>Virtual screening, molecular dynamics simulations, MM-GBSA free energy calculations, and principal component analysis were performed using the Schrödinger Desmond software to screen a comprehensive library from the NPACT and PhytoHub databases for potential novel TrkA inhibitors.</p><p><strong>Results: </strong>Two promising inhibitors derived from natural compounds, PHUB000399 and NPACT01417, were identified. Toxicity assessments indicated that both compounds had lower toxicity levels (class 5) than Entrectinib, the reference inhibitor (class 4); the molecular weights of PHUB000399, NPACT01417, and Entrectinib were 275.25, 316.35, and 560.64 g/mol, respectively. Docking studies showed that PHUB000399 and NPACT01417 had superior binding affinities, with grid scores of -13.239 and -13.103, respectively, compared with the co-crystal ligand (-12.567) and Entrectinib (-10.996). Molecular dynamics simulations indicated that the TrkA-PHUB000399 and TrkA-NPACT01417 complexes were more stable than the TrkA-Entrectinib complex. The calculated binding free energies for TrkA-PHUB000399 and TrkA-NPACT01417 were -87.74 and -86.09 kcal/mol, respectively, exceeding those of the co-crystal ligand (-84.14 kcal/mol) and Entrectinib (-73.03 kcal/mol).</p><p><strong>Conclusions: </strong>These findings suggest that NPACT01417 and PHUB000399 are promising candidates for targeting cancer cell migration, with binding affinities comparable to those of established inhibitors. This study provides valuable insights for the development of effective anticancer therapies.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e166946"},"PeriodicalIF":1.7,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, Molecular Docking, and Preclinical Evaluation of a New Radiolabeled PEG3-Linked FAPI Derivative for Fibroblast Activation Protein Targeting.","authors":"Mahshid Kiani, Mehdi Akhlaghi, Safura Jokar, Omid Bavi, Hooman Hafezi, Khosrou Abdi, Omid Sabzevari, Saeed Balalaie, Farhad Golmohammadi, Zahra Ghiamaty, Sara Roustaei, Alireza Foroumadi, Davood Beiki","doi":"10.5812/ijpr-170734","DOIUrl":"10.5812/ijpr-170734","url":null,"abstract":"<p><strong>Background: </strong>Fibroblast activation protein (FAP) is a promising molecular target for cancer theranostic applications. However, current fibroblast activation protein inhibitors (FAPIs) have limitations, including rapid clearance and limited tumor retention.</p><p><strong>Objectives: </strong>This study aimed to develop a novel PEG₃-linked FAPI derivative, [⁶⁸Ga]Ga-FAPI-MKG, with enhanced tumor accumulation and retention. FAPI-MKG was prepared by incorporating a PEG₃ linker into the FAPI-04 structure to optimize its pharmacokinetic profile.</p><p><strong>Methods: </strong>The compound was synthesized via an 11-step route starting from quinine sulfate and radiolabeled with gallium-68. In vitro studies included determination of lipophilicity (Log P) and stability assays in saline and human serum albumin. Preclinical evaluation in BALB/c mice bearing CT-26 tumors included biodistribution, blocking studies, and PET/CT imaging. Molecular docking and molecular dynamics simulations were performed to provide mechanistic insights into binding interactions.</p><p><strong>Results: </strong>[⁶⁸Ga]Ga-FAPI-MKG was successfully synthesized with high radiochemical purity (> 98%) and a molar activity of 414.79 mCi/μmol. It demonstrated moderate hydrophilicity (Log P = -3.26 ± 0.18) compared with the reference radiotracer, [⁶⁸Ga]Ga-FAPI-46 (-3.58 ± 0.29), and high stability (RCP > 90% after 120 minutes). In vivo studies showed significantly higher tumor uptake (7.18 ± 0.56% ID/g at 60 minutes; 3.20 ± 0.11% ID/g at 120 minutes) and prolonged retention compared with the reference radiotracer, along with dual hepatobiliary and renal excretion pathways. Blocking studies confirmed FAP-specific uptake. Computational analyses indicated strong binding energy (-9.8 kcal/mol) and optimized electrostatic interactions with FAP. The strategic incorporation of a PEG₃ linker into [⁶⁸Ga]Ga-FAPI-MKG significantly improved tumor accumulation, extended tumor retention, and increased the tumor-to-background ratio.</p><p><strong>Conclusions: </strong>These findings suggest that [⁶⁸Ga]Ga-FAPI-MKG may be a promising candidate for clinical translation for imaging and theranostics of FAP-expressing cancers.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e170734"},"PeriodicalIF":1.7,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561990","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":"Elucidating the Molecular Mechanisms of <i>Angelica sinensis</i> Against Hepatocellular Carcinoma Through Network Pharmacology, in silico Molecular Docking, and in vitro Validation.","authors":"Huajun Wu, Ping Luo, Chongming Shen","doi":"10.5812/ijpr-169852","DOIUrl":"10.5812/ijpr-169852","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hepatocellular carcinoma (HCC) is a lethal liver malignancy associated with substantial morbidity and mortality and remains a major socioeconomic burden worldwide. Given the high risk associated with HCC, novel therapeutic approaches are urgently needed. &lt;i&gt;Angelica sinensis&lt;/i&gt; is a traditional Chinese herbal remedy that contains bioactive phytochemicals with promising anticancer properties, making it a potential candidate for evaluation in HCC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This study integrated computational network pharmacology, molecular docking, and in vitro cellular assays to elucidate the mechanisms by which &lt;i&gt;A. sinensis&lt;/i&gt; exerts anti-HCC effects in Hep-G2 cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Phytochemicals were identified using the Traditional Chinese Medicine Systems Pharmacology database and filtered according to drug-likeness and oral bioavailability criteria. Key compounds (β-sitosterol, alpha-cephalin, sitogluside, and stigmasterol) were further analyzed using the SuperPred Target Prediction tool to predict potential targets. HCC-related targets were curated from GeneCards and refined using the GeneCards Inferred Functionality Score. The overlap between compound-related and disease-specific targets was used to construct a protein-protein interaction network using STRING, which was subsequently visualized in Cytoscape to identify hub genes. Molecular docking between stigmasterol and the top 3 hub genes was evaluated using the CB-Dock2 online server, and all preparations were performed in BIOVIA Discovery Studio. In vitro, Hep-G2 cells were treated with varying concentrations (0, 25, 50, 100, and 200 µg/mL) of &lt;i&gt;A. sinensis&lt;/i&gt; extract. Cell viability, clonogenic potential, apoptosis induction, and migratory capacity were evaluated using the MTT assay, clonogenic assay, Annexin V/PI staining, and Transwell migration assay, respectively. Western blotting was used to assess the expression of key hub proteins in Hep-G2 cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In silico analysis identified an initial pool of 126 phytochemicals, which was refined to 4 key compounds yielding 139 unique targets. Intersection with HCC-related targets produced 123 common targets, generating a network comprising 119 nodes and 520 edges. STAT3, NFKB1, and TLR4 were identified as pivotal hub genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the hub genes demonstrated significant enrichment in HCC-related pathways and biological processes. Molecular docking indicated a strong binding affinity of stigmasterol to STAT3, NFKB1, and TLR4, with binding energies of -7.8, -6.9, and -6.9 kcal/mol, respectively. In vitro assays showed a dose-dependent reduction in Hep-G2 cell viability and colony formation, significant induction of apoptosis, and marked inhibition of migration. Western blotting confirmed significant downregulation of STAT3, NFKB1, and TLR4 expression at higher extract concentratio","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169852"},"PeriodicalIF":1.7,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562004","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":"Metformin Attenuates Angiotensin II-Induced Cardiac Inflammaging-Like Injury Through Coordinated Nrf2 Activation and NF-κB Suppression.","authors":"Huarui Li, Deming Fu, Umar Saeed, Zahra Zahid Piracha, Jianjun Bao","doi":"10.5812/ijpr-170947","DOIUrl":"10.5812/ijpr-170947","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Age-related cardiomyocyte vulnerability is driven by a convergent triad of persistent oxidative stress, chronic low-grade inflammation, and senescence-like signaling, which together accelerate functional decline and maladaptive remodeling. Angiotensin II (Ang II), a clinically relevant stress effector, amplifies reactive oxygen species (ROS) production and inflammatory activation, thereby impairing cardiomyocyte survival and repair capacity. Although metformin has emerging cardiovascular benefits beyond glycemic control, its coordinated capacity to counteract Ang II-driven inflammaging-like injury through the coupled regulation of antioxidant and anti-inflammatory pathways in human cardiomyocytes remains insufficiently defined.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This study aimed to determine whether metformin attenuates Ang II-induced injury and impaired repair in human AC16 cardiomyocytes and to evaluate whether this protection is associated with coordinated activation of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and suppression of Nuclear Factor-κB (NF-κB).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Human AC16 cardiomyocytes were preconditioned with metformin (0.5 or 1.0 mM) for 2 h and then challenged with Ang II (0.1 - 2.0 μM) under continuous metformin exposure. The primary efficacy endpoints were cell survival, quantified using the MTT assay, and repair competence, assessed by scratch wound closure. Secondary mechanistic endpoints included inflammatory mediators (TNFA, IL6, and IL1B); senescence-associated markers (CDKN2A/p16 and CDKN1A/p21); antioxidant genes linked to Nrf2 signaling (NFE2L2/Nrf2, HMOX1/HO-1, and NQO1); NF-κB pathway activation; antioxidant and apoptosis-related proteins; Nrf2 compartmentalization; and intracellular ROS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Angiotensin II induced a dose-dependent injury phenotype in AC16 cardiomyocytes, reducing viability from 100.0 ± 1.1% in control cells to 64.9 ± 1.6% at 1.0 μM and 53.0 ± 1.6% at 2.0 μM, while markedly impairing wound closure (80.0 ± 2.0% in control vs 32.3 ± 2.5% with Ang II). Metformin attenuated this injury in a concentration-dependent manner, restoring viability to 81.7 ± 1.0% with 0.5 mM and 89.7 ± 1.0% with 1.0 mM and improving wound closure to 52.3 ± 2.5% and 70.0 ± 2.0%, respectively. Angiotensin II also robustly increased inflammatory cytokine expression, with TNFA, IL6, and IL1B increasing to 27.86 ± 2.79-fold, 29.86 ± 2.99-fold, and 29.86 ± 2.99-fold, respectively, accompanied by NF-κB activation, ROS accumulation (187.7 ± 2.5% of control), apoptosis-associated signaling, and upregulation of the senescence-like markers p16 and p21. Metformin markedly suppressed these responses, reducing cytokine expression toward near-baseline levels, lowering ROS to 120.0 ± 2.0%, decreasing the BAX/BCL-2 ratio from 2.98 to 1.19, and reducing cleaved caspase-3 and cleaved PARP to 120% and 112% of control, respectively. In parallel, metformin enhanced ","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e170947"},"PeriodicalIF":1.7,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591792","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":"Andrographolide Alleviates <i>Mycoplasma pneumoniae</i> Pneumonia in Children by Inhibiting Alveolar Epithelial Cell Pyroptosis Through the HMGB1/TLR4/NF-κB Pathway.","authors":"Lijuan Zhang, Umar Saeed, Rui Gao","doi":"10.5812/ijpr-169826","DOIUrl":"10.5812/ijpr-169826","url":null,"abstract":"<p><strong>Background: </strong><i>Mycoplasma pneumoniae</i> pneumonia (MPP) is a pulmonary inflammatory disease caused by <i>Mycoplasma pneumoniae</i> (Mp) infection that primarily involves the bronchi, alveoli, and pulmonary interstitium. It is the most common cause of community-acquired pneumonia in children. Andrographolide (AG) is a natural diterpenoid lactone with anti-inflammatory and immunomodulatory activities; however, its specific role and mechanism in MPP remain unclear.</p><p><strong>Objectives: </strong>This study aimed to investigate the mechanism by which AG inhibits pyroptosis in alveolar epithelial cells via the HMGB1/TLR4/NF-κB signaling pathway in the treatment of MPP in children.</p><p><strong>Methods: </strong>Mp-stimulated MLE-12 cells were treated with AG at 10, 20, or 50 μM. Cell viability and injury were assessed using CCK-8 and LDH assays, respectively. Protein expression levels of NLRP3, HMGB1, TLR4, and p-NF-κB p65 were determined by Western blotting, and cytokine levels (IL-6 and TNF-α) were measured by ELISA. In an Mp-infected mouse model, mice received AG at 25 or 50 mg/kg. Body weight, lung index, lung histopathology, pathway-related protein expression, and cytokine levels (IL-1β and TNF-α) in bronchoalveolar lavage fluid (BALF) were evaluated.</p><p><strong>Results: </strong>Mp significantly induced cytotoxicity, pyroptosis, and inflammation in vitro and in vivo (all P < 0.001). Andrographolide treatment dose-dependently reduced LDH release, suppressed HMGB1/TLR4/NF-κB/NLRP3 activation, and decreased proinflammatory cytokine levels (P < 0.05). In mice, AG improved survival-related metrics, ameliorated lung pathology, and inhibited pathway activity and cytokine secretion.</p><p><strong>Conclusions: </strong>Andrographolide mitigates MPP via the HMGB1/TLR4/NF-κB signaling pathway by inhibiting pulmonary epithelial cell pyroptosis and inflammation. These findings indicate its potential as a therapeutic agent.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e169826"},"PeriodicalIF":1.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591757","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":"Apigenin for Depression and Anxiety: A Systematic Review of Preclinical Studies.","authors":"Jin Wang, Kun Shi","doi":"10.5812/ijpr-167153","DOIUrl":"10.5812/ijpr-167153","url":null,"abstract":"<p><strong>Context: </strong>Depression and anxiety are debilitating disorders with complex pathophysiologies associated with neurotransmitter deficits, neuroinflammation, and oxidative stress. Apigenin, a dietary flavonoid, has therapeutic potential because of its neuroprotective properties.</p><p><strong>Evidence acquisition: </strong>We assessed the antidepressant and anxiolytic effects of apigenin in rodent models, focusing on behavioral outcomes, mechanisms involving neuroinflammation, oxidative stress, and neurotransmitter balance, and relevant molecular pathways. A systematic search of PubMed, Scopus, and Embase was conducted through July 2025. In vivo rodent studies evaluating the effects of apigenin on depression or anxiety were included. Exclusion criteria comprised studies addressing other disorders, apigenin derivatives, or non-original research. Data on study design, model, treatment, outcomes, and mechanisms were extracted.</p><p><strong>Results: </strong>Of 953 screened records, 21 studies met the inclusion criteria. Preclinical evidence consistently indicated that apigenin ameliorated depressive- and anxiety-like behaviors across diverse rodent models, frequently demonstrating effects comparable to or greater than those of conventional pharmacological treatments. Mechanistically, apigenin mediated its neuropsychological effects through multiple pathways, including reducing oxidative and nitrosative stress, inhibiting neuroinflammation, modulating monoaminergic neurotransmission, upregulating neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB), and regulating energy metabolism and neurogenesis. Apigenin exhibited a favorable safety profile across all included studies, even at high doses.</p><p><strong>Conclusions: </strong>In rodent models, apigenin exhibits substantial antidepressant and anxiolytic effects through complex mechanisms involving redox modulation, anti-inflammatory activity, neurotransmitter regulation, and neurotrophic support. These findings indicate that apigenin warrants further translational investigation and potential therapeutic development for treating depression and anxiety disorders.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e167153"},"PeriodicalIF":1.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562021","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 Impact of Marijuana (<i>Cannabis sativa</i>) on Viability and Expression of Cardiac Markers in Human Cardiomyocytes.","authors":"Hossein Kargar Jahromi, Vida Khalafi, Vida Mirzaei, Faezeh Ebrahimi-Zadeh, Pouria Azami, Tara Abdolahy, Iman Razeghian-Jahromi","doi":"10.5812/ijpr-168324","DOIUrl":"10.5812/ijpr-168324","url":null,"abstract":"<p><strong>Background: </strong><i>Cannabis sativa</i> has been used since antiquity for medicinal, ceremonial, and agricultural purposes. Today, cannabis, commonly known as marijuana, remains the most widely used recreational drug worldwide. As its use increases, particularly among young adults, reports of adverse effects on vital organs have also increased. This trend underscores the need for a comprehensive assessment of marijuana's effects on the cardiovascular system.</p><p><strong>Objectives: </strong>This study aimed to investigate the effects of <i>C. sativa</i> extract on the viability, proliferation, and expression of cardiac markers in human cardiomyocytes.</p><p><strong>Methods: </strong>Human cardiomyocytes (HCMs) were cultured and subsequently exposed to varying concentrations of cannabis extract. Cell viability was assessed using the MTT assay, and morphological changes were examined on days 3 and 6. Growth curves and population doubling times were determined over a 6-day period using the trypan blue exclusion method. In addition, the expression levels of cardiac-specific markers, including GATA4, troponin, and creatine kinase, were quantified using real-time polymerase chain reaction on days 1, 3, and 6.</p><p><strong>Results: </strong>No significant changes in cell morphology were observed; however, cell density was consistently higher in the treated group, particularly at early time points. Growth-curve analysis confirmed these findings, demonstrating higher cell numbers in treated cultures throughout the study period, consistent with the population doubling time data (74.79 h in the treated group vs. 80.45 h in the control group, P = 0.005). Furthermore, the treated group exhibited increased expression of cardiac-specific markers compared with the controls, most notably between day 1 and day 3 (GATA4: 7.97 ± 1.06 vs. 1.48 ± 0.64, P < 0.05; troponin: 3.52 ± 0.85 vs. 1.13 ± 0.92, P = 0.05; creatine kinase: 0.001 ± 0.0008 vs. 1.22 ± 0.90, P = 0.05).</p><p><strong>Conclusions: </strong><i>Cannabis sativa</i> extract increased proliferation and upregulated the expression of cardiac genes in HCMs. These changes may impair normal cardiomyocyte function, which is vital for cardiovascular health. This issue is particularly important given the increasing global consumption of cannabis-derived substances, driven in part by expanding legalization.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"25 1","pages":"e168324"},"PeriodicalIF":1.7,"publicationDate":"2026-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561956","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}