Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Protective Effect of Melissa officinalis (Lemon Balm) Extract on Cytokine Levels and Oxidative Stress in Ovalbumin Induced Lung Toxicity in Rats","authors":"Vahideh Abbasnia,&nbsp;Mohsen Foadoddini,&nbsp;Mohammad Reza Khazdair","doi":"10.1111/bcpt.70068","DOIUrl":"https://doi.org/10.1111/bcpt.70068","url":null,"abstract":"<div>\u0000 \u0000 <p>This study assessed the effects of a hydroalcoholic extract derived from <i>Melissa officinalis</i> (lemon balm) at doses of 50, 100 and 200 mg/kg in a rat model of experimental allergic asthma. We evaluated biomarkers of oxidative stress, including nitrite (NO₂), malondialdehyde (MDA), thiol (SH), superoxide dismutase (SOD) and catalase (CAT), along with mediators such as interleukin-4 (IL-4), IL-17, interferon-gamma (IFN-γ) and immunoglobulin E (IgE) in bronchoalveolar lavage fluid (BALF). The untreated asthmatic group showed significantly elevated levels of MDA, NO₂, IL-4, IL-17 and IgE (<i>p</i> &lt; 0.001), while levels of SH, IFN-γ and the activities of SOD and CAT were markedly reduced compared with the control group. In contrast, treatment groups receiving plant extracts and dexamethasone (Dex) demonstrated a significant decrease in levels of NO₂, MDA, IL-4, IL-17 and IgE. Additionally, the levels of SH, IFN-γ and the activities of SOD and CAT were significantly elevated compared with the untreated asthmatic group (<i>p</i> &lt; 0.05 to <i>p</i> &lt; 0.001). The therapeutic efficacy of <i>Melissa officinalis</i> extract in reducing oxidative damage and inflammatory mediators in asthmatic rats was comparable to that of dexamethasone. This finding highlights the potential therapeutic benefits of the plant in alleviating asthma-related symptoms.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214183","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":"Traditional Chinese Medicine for Anti-Arrhythmias: Mechanisms via Potassium Channels","authors":"Chenhao Gao,&nbsp;Ting Xu,&nbsp;Lingyu Linda Ye,&nbsp;Dayue Darrel Duan","doi":"10.1111/bcpt.70059","DOIUrl":"https://doi.org/10.1111/bcpt.70059","url":null,"abstract":"<p>Cardiac arrhythmia is a common life-threatening cardiovascular disorder. Potassium channels play a crucial role in cardiac electrophysiology, and their dysfunction is closely associated with the occurrence and development of arrhythmia. Traditional Chinese medicine (TCM) has a long-standing history of treating various diseases, including arrhythmia and offers a rich source of compounds for anti-arrhythmic drugs. To provide in-depth new insights for the development of novel anti-arrhythmic therapies, this review delves into the effects of TCM on potassium channels through multiple ways, including the direct interaction between the active ingredients contained and potassium channels, regulation of the expression of related genes and proteins, intervention in intracellular signalling pathways and exertion of antioxidant and anti-inflammatory effects. With continued efforts in standardization, research and integration with Western medicine, TCM is playing an increasingly important role in the treatment of arrhythmia and provides novel options for patients worldwide. Phenomics and pharmacophenomics as well as the artificial intelligence–based GPCR ligand screening system may provide new paradigms and platforms for discovering and developing more anti-arrhythmic drugs.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197476","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":"Real-World Complexity of Prescribing Cascades","authors":"J. T. H. Nielen,&nbsp;K. van der Walle,&nbsp;S. H. Spronk,&nbsp;F. J. H. Magdelijns,&nbsp;P. Denig,&nbsp;F. Karapinar-Çarkıt","doi":"10.1111/bcpt.70063","DOIUrl":"https://doi.org/10.1111/bcpt.70063","url":null,"abstract":"<p>Prescribing cascades occur when an adverse drug reaction (ADR) to one medication is treated with additional medication. Most literature focusses on this simplistic singular concept of one medication followed by another. However, ADRs in clinical practice may appear less straightforward, making prescribing cascades difficult to identify and deprescribe. More insight is needed into the real-world complexity of prescribing cascades, since they may negatively impact both patients and the healthcare system. This article aims to provide exemplary cases of the real-world complexity of prescribing cascades and explores strategies to identify, mitigate and prevent them. The real-world cases discussed highlight the multifaceted nature of prescribing cascades in clinical practice. They show several factors contributing to the challenges in recognizing ADRs and preventing prescribing cascades, including misinterpretation of ADRs, fragmented healthcare systems and accumulation of pharmacological effects and comorbidities within an individual patient. Several strategies are recommended to improve identification, mitigation and prevention of prescribing cascades. Although educating patients and healthcare providers (HCPs) can help bridge the knowledge gap, additional strategies are needed. Implementing supportive tools to deprescribe, enhanced communication among HCPs and patients regarding ADRs and rationale for medication changes, and monitoring patients for ADRs are considered the most promising strategies.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197299","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":"Therapeutic Targeting of the α7 Nicotinic Receptor: Challenges and Prospects for Cognitive Improvement in Alzheimer's and Schizophrenia","authors":"Janus H. Magnussen","doi":"10.1111/bcpt.70061","DOIUrl":"https://doi.org/10.1111/bcpt.70061","url":null,"abstract":"<p>The α7 nicotinic acetylcholine receptor (α7 nAChR) has emerged as a key target for treating cognitive dysfunction in neurological disorders such as Alzheimer's disease (<span>AD</span>) and schizophrenia. α7 nAChRs play essential roles in neurotransmission, neuroinflammation and synaptic plasticity, not only in neurons but also in glial cells, where they engage in metabotropic signalling. Despite promising preclinical findings, clinical trials of α7 nAChR agonists, partial agonists and positive allosteric modulators (PAMs) have yielded inconsistent results, with few achieving sustained cognitive benefits in patients. This review examines the functional properties of α7 nAChRs, ionotropic and metabotropic signalling roles, and their contribution to cognitive processes in <span>AD</span> and schizophrenia. We provide a comprehensive analysis of key α7-targeted compounds that advanced to clinical trials, detailing their outcomes and challenges. Additionally, we discuss major translational barriers, including receptor desensitization, pharmacokinetic limitations, inter-individual variability (e.g., effects of smoking on metabolism) and species differences in preclinical models. Finally, we explore innovative strategies to improve trial success, including optimized dosing regimens, co-administration with PAMs and neuroimaging techniques like PET to refine patient selection and drug evaluation. These approaches may offer a more effective pathway for developing α7-targeted cognitive therapies in <span>AD</span> and schizophrenia.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197300","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":"Liquiritigenin-Rich Hydroalcoholic Extract of Brazilian Red Propolis Reduces Dyskinesia Induced by 3,4- Dihydroxyphenylalanine in Hemiparkinsonian Rats","authors":"Sheilla da Silva Barroso,&nbsp;Lorenna E. S. Lopes,&nbsp;Ana M. G. dos Santos,&nbsp;Reinaldo V. B. Neto,&nbsp;Bruno dos Santos Lima,&nbsp;Adriano A. de Souza Araújo,&nbsp;Juliana C. Cardoso,&nbsp;Patricia Severino,&nbsp;Eliana B. Souto,&nbsp;Margarete Z. Gomes","doi":"10.1111/bcpt.70062","DOIUrl":"https://doi.org/10.1111/bcpt.70062","url":null,"abstract":"<p>The set-up and progression of dyskinesia induced by 3,4-dihydroxyphenylalanine (L-DOPA) are strongly linked to oxidative stress and neuroinflammation. The aim of this work was to study and characterize the effects of the hydroalcoholic extract of Brazilian red propolis (HERP) on L-DOPA–induced dyskinesia (LID) in hemiparkinsonian rats injected with 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB). The abnormal involuntary movements (AIM) and spontaneous motor parameters were evaluated over 21 days of treatment, and then immunohistochemistry for glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH) was performed on rat brains. The presence of biochanin A, formononetin and the major compound liquiritigenin in HERP was confirmed by HPLC-DAD. HERP presented a high antioxidant effect in vitro, while in vivo the locomotive, orolingual, limb and axial dyskinetic effects of L-DOPA were counteracted with 10 mg/kg of HERP and 40 mg/kg of amantadine (AMAN). However, HERP alone did not reduce antiparkinsonian effects of L-DOPA in behavioural assessment. Immunostaining showed that L-DOPA increased GFAP expression, which was decreased by HERP and AMAN. HERP decreased the ipsilateral loss of TH expression, whereas HERP and AMAN increased contralateral expression of TH at the mesencephalon. HERP induced antidyskinetic effects in rats, with motor improvement, which is an advancement in comparison to standard medications, and these effects may be mediated by astrocyte-related mechanisms.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197301","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":"Eugenol Alleviates Cerebral Ischemia–Reperfusion Injury in Mice by Promoting the Phagocytosis of Microglia via Up-Regulating Tripartite Motif Protein 59","authors":"Mengtian Pan,&nbsp;Xiang Li,&nbsp;Xinjuan Tian,&nbsp;Lele Zixin Yang,&nbsp;Weirong Fang","doi":"10.1111/bcpt.70058","DOIUrl":"https://doi.org/10.1111/bcpt.70058","url":null,"abstract":"<div>\u0000 \u0000 <p>Ischemic stroke (IS) is one of the most sinister diseases and the second leading cause of death in the world. Eugenol (EUG) is a natural and biologically active component that can be extracted from various plants. Studies have found that EUG can alleviate middle cerebral artery occlusion and reperfusion (MCAO/R) injury in mice, but the specific mechanism remains vague. Tripartite motif protein 59 (TRIM59) is a member of TRIM protein family, a group of E3 ubiquitin ligases. In this article, we conducted both in vivo and in vitro experiments to determine the effect of EUG on ischemia–reperfusion injury and to explore the underlying mechanisms by manipulating the expression of TRIM59. Results showed that EUG alleviates acute injury and promotes functional repair of mouse IS by enhancing the phagocytosis of microglia through up-regulating the TRIM59, activating the STAT3 pathway and promoting the expression of CD11b.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148549","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":"Healthcare Providers' Perspectives on Antidepressant Discontinuation: A Focus Group Study","authors":"S. Bouarfa,&nbsp;Wilma Göttgens,&nbsp;Suzanne A. Ligthart,&nbsp;Otto R. Maarsingh,&nbsp;Christiaan H. Vinkers,&nbsp;Henricus G. Ruhé,&nbsp;Pierre M. Bet,&nbsp;Jacqueline G. Hugtenburg","doi":"10.1111/bcpt.70051","DOIUrl":"https://doi.org/10.1111/bcpt.70051","url":null,"abstract":"<p>Antidepressant (<span>AD</span>) discontinuation in long-term users can be challenging for both patients and healthcare providers (HCPs). Better understanding of how HCPs handle this challenge is needed to improve discontinuation care. Therefore, we identified <span>AD</span> discontinuation barriers and facilitators from the viewpoint of community pharmacists (CPs), general practitioners (GPs), psychiatrists and nurse practitioners and explored their views on their specific roles in <span>AD</span> discontinuation. Two focus group discussions involving four GPs, six pharmacists and three psychiatrists and one interview with a nurse practitioner were performed. Discussions were recorded and transcribed verbatim. Directed content analysis was performed using the theoretical domains framework. Six themes were identified: identification of patients, behaviour of HCPs regarding <span>AD</span> discontinuation, fears and emotions, context and resources, knowledge, evidence and skills and professional attitude. All HCPs stressed the importance of raising awareness for <span>AD</span> discontinuation. Barriers included fear of recurrence or discontinuation symptoms, poor collaboration between HCPs and lack of resources. Facilitators included the availability of tools and guidelines. HCPs were unaware and uncertain about each other's roles and responsibilities and showed motivation to provide guidance. This requires professional collaboration agreements and sufficient resources. Experienced CPs may contribute by identifying <span>AD</span> users and providing information/support.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135824","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":"Trends in Proton-Pump Inhibitor Use Among Danish Adults: A Nationwide Drug Utilization Study 2015–2023","authors":"Karoline M. Lundgaard,&nbsp;Morten Ø. Christiansen,&nbsp;Heidi Sonne,&nbsp;Katrine Mose,&nbsp;Nikolaj Nyland,&nbsp;Maja J. L. Andersen,&nbsp;Anton Pottegård","doi":"10.1111/bcpt.70057","DOIUrl":"https://doi.org/10.1111/bcpt.70057","url":null,"abstract":"<p>The global increase in proton-pump inhibitor (PPI) use has raised concerns about their appropriate use, particularly due to potential overprescription and associated adverse effects. This study examines PPI utilization patterns among Danish adults from 2015 to 2023 using the Danish nationwide health registries. We estimated the annual incidence rate (users per 100 person-years) and monthly prevalence (proportion with a filled prescription or sufficient tablets). Treatment duration was assessed using the ‘proportion of patients covered’ and the Kaplan–Meier method. We also calculated the proportion of adults with concomitant use of ulcerogenic drugs over time. We identified 1 729 440 adults who filled at least one PPI prescription during 2015–2023. The prevalence increased from 7.0% in 2015 to 8.2% in 2023, while incidence rate remained stable at ~3 users per 100 person years. PPI use increased with age. Three years after initiation, 17% used PPIs, while 1.5% had remained on continuous treatment. In 2023, 50% of users had concomitant ulcerogenic drug use, a 3.2% increase since 2015. The prevalence of PPI use in Denmark has risen markedly reaching a high stable level, with a clear age-dependent trend. Increased attention to appropriate PPI use is necessary to ensure rational prescribing and prevent potential overuse.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135825","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":"Deprescribed or Discontinued? Addressing Terminology Misinterpretation in Research","authors":"Caroline Sirois,&nbsp;Alexandre Campeau Calfat,&nbsp;Justin P. Turner","doi":"10.1111/bcpt.70054","DOIUrl":"https://doi.org/10.1111/bcpt.70054","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085345","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":"TCA Cycle Intermediate Mitigates Di(2-ethylhexyl) Phthalate-Induced Cholestatic Liver Injury Through Modulation of the Nrf2/NQO1 Signalling Axis","authors":"Yue Jiang,&nbsp;Fang Xie,&nbsp;Xutao Ling,&nbsp;Jiayi Zhang,&nbsp;Yun Yu,&nbsp;Qianqian Huang,&nbsp;Lun Zhang,&nbsp;Lu Ye,&nbsp;Wenkang Tao,&nbsp;Mengzhen Hou,&nbsp;Cheng Zhang,&nbsp;Jianqing Wang","doi":"10.1111/bcpt.70047","DOIUrl":"https://doi.org/10.1111/bcpt.70047","url":null,"abstract":"<div>\u0000 \u0000 <p>As a commonly used phthalate compound, di(2-ethylhexyl) phthalate (DEHP) has been shown to disrupt the tricarboxylic acid (TCA) cycle and aggravate tissue damage. However, whether the TCA cycle is involved in cholestatic liver injury (CLI) induced by DEHP and the protective effect of dimethyl fumarate (DMF), which is used to supplement TCA intermediate metabolites, remained unclear. Here, mice were randomized into five groups (<i>n</i> = 6/group): (1) Control, (2) DEHP (200 mg/kg/day), (3) DMF (100 mg/kg/day), (4) DEHP + DMF (30 mg/kg/day) and (5) DEHP + DMF (100 mg/kg/day). Our data demonstrated that DEHP exposure upregulated total bile acid (TBA) levels and broke the TCA cycle, resulting in reduced fumaric acid and malic acid. However, we further supplemented fumaric acid with DMF and found that DMF effectively reversed the high levels of TBA, alkaline phosphatase (ALP) and glutamyl transpeptidase (GGT) induced by DEHP in mice. Meanwhile, pathological results in the liver showed that DMF improved bile duct cell damage, inflammatory cell infiltration, collagen deposition and necrosis caused by DEHP. In addition, we found that DEHP elevated the level of interleukin (IL)-1β, IL-6, TNF-α and MDA and decreased the level of SOD in the mouse liver, which was effectively reversed by DMF treatment. Besides, DMF upregulated the expression of Nrf2 and NQO1 in the liver of DEHP-exposed mice. For in vitro validation, AML-12 cells were treated with (1) Control, (2) DEHP (250 μM), (3) DEHP + DMF (10 μM), (4) DEHP + DMF (25 μM) and (5) DEHP + DMF (50 μM). DEHP exposure increased the expression of IL-1β, IL-6 and TNF-α, which was mitigated by DMF, while ML385, an Nrf2 inhibitor, could counteract the anti-inflammatory effects of DMF. These findings indicate that DEHP broke the TCA cycle of the mouse liver, and DMF supplementation protects against DEHP-induced CLI by activating the Nrf2/NQO1 pathway.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950216","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}