Pharmacological Reports最新文献

{"title":"Effects of magnolol on the liver antioxidant status in rats with diabetes.","authors":"Sławomir Dudek, Weronika Borymska, Maria Zych, Dżesika Chełminiak, Magdalena Kimsa-Dudek, Ilona Kaczmarczyk-Żebrowska","doi":"10.1007/s43440-025-00718-5","DOIUrl":"https://doi.org/10.1007/s43440-025-00718-5","url":null,"abstract":"<p><strong>Background: </strong>Magnolol isolated from Magnolia (Magnolia sp.) flowers are used to support the treatment of diabetes. The aim of this study was to investigate the effects of magnolol on the liver antioxidant status in rats with type 2 diabetes and assess oxidative stress parameters at both biochemical and molecular levels.</p><p><strong>Methods: </strong>Mature male Wistar rats with high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetes were administered magnolol at doses of 5 or 25 mg/kg body weight po for 4 weeks. Then, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), the concentrations of advanced protein oxidation products (AOPPs) and malondialdehyde (MDA), the total antioxidant response (TAR), and the total oxidative status (TOS) were assessed using commercially available colorimetric kits according to the manufacturers' protocols. The mRNA levels of the cytochrome P450 family 1 subfamily A member 2 (CYP1A2), cytochrome P450 family 2 subfamily E member 1 (CYP2E1), nuclear factor erythroid 2-related factor 2 (NFE2L2), and Kelch like ECH-associated protein 1 (KEAP1) genes were determined using real-time quantitative reverse transcription-polymerase chain reaction (RT‒qPCR). All parameters were analyzed in liver samples.</p><p><strong>Results: </strong>Compared with 5 mg/kg magnolol, 25 mg/kg magnolol had a more beneficial effect on several indicators of oxidative stress in the liver observed as significant decreases in the activity of SOD and CAT, as well as decreased MDA concentrations. Further, significant increases in the concentrations of AOPPs and native thiols were observed. The gene encoding CYP2E1 was upregulated in diabetic rats compared with control rats. Moreover, compared with diabetic rats, diabetic rats treated with 25 mg/kg magnolol presented increased expression of the KEAP1 gene.</p><p><strong>Conclusions: </strong>The induction of diabetes is known to disturb redox homeostasis. The administration of magnolol at the higher dose used in this study, might counteract the changes in the liver antioxidant status at both the molecular and biochemical levels. Owing to the positive alterations in some oxidative stress parameters, after further in-depth study, magnolol may be considered a promising compound that could be used to complement diabetes treatment.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the role of Na⁺/K⁺-ATPase pump: neurodegenerative mechanisms and therapeutic horizons.","authors":"Ramandeep Kaur Sidhu, Kousik Maparu, Shamsher Singh, Khadga Raj Aran","doi":"10.1007/s43440-025-00717-6","DOIUrl":"https://doi.org/10.1007/s43440-025-00717-6","url":null,"abstract":"<p><p>Sodium and potassium-activated adenosine 5'-triphosphatase (Na+/K+-ATPase) is a pivotal plasma membrane enzyme involved in neuronal activity and cellular homeostasis. The dysregulation of these enzymes has been implicated in a spectrum of neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and neurodevelopmental disorders including autism spectrum disorder (ASD), psychiatric disorders such as schizophrenia, and neurological problems like epilepsy. A hallmark of these disorders is the gradual loss of neuronal integrity and function, often exacerbated by protein accumulation within brain cells. This review delves into the multifaceted role of Na⁺/K⁺-ATPase dysfunction in driving oxidative stress, excitotoxicity, and neuroinflammation, contributing to synaptic and neuronal damage. Emerging therapeutic strategies, such as gene therapy and developing isoform-specific enzyme modulators, offer promising avenues for targeted interventions. Furthermore, this review highlights innovative research directions, including the role of Na⁺/K⁺-ATPase in synaptic plasticity, the identification of endogenous regulators, and its contribution to neuroinflammatory pathways. Personalized medicine and advanced gene-editing technologies are positioned as transformative tools for crafting safer and more precise therapies tailored to individual patients. This comprehensive exploration underscores the enzyme's therapeutic potential and sets the stage for developing novel targeted strategies to mitigate the burden of Na⁺/K⁺-ATPase-linked neurological disorders.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formyl peptide receptor 2: a potential therapeutic target for inflammation-related diseases.","authors":"Jiaying Wang, Zhishuo Miao, Yinhuang Gao, ZhiZhong Xie, Menghua Liu, Wei Zou","doi":"10.1007/s43440-025-00704-x","DOIUrl":"https://doi.org/10.1007/s43440-025-00704-x","url":null,"abstract":"<p><p>Formyl peptide receptor 2 (FPR2) is a G protein-coupled receptor with seven transmembrane domains, widely distributed in human cells. It plays a crucial role in inflammation-related diseases. Known for its \"double-edged sword\" nature, FPR2 can bind a variety of exogenous and endogenous ligands, mediating both pro-inflammatory and anti-inflammatory responses in tissues such as eyes, liver, joints, lungs, nerves, and blood vessels. FPR2's bioactivities are regulated by a complex network of genes and signaling pathways. However, the precise regulatory mechanisms governing its functions in different inflammatory conditions are still not well understood. This review summarizes the FPR2's activities in various inflammation-related diseases and looks into its potential as a therapeutic target. This review highlights recent advances in developing exogenous agonists for FPR2 and discusses receptor expression across species to support nonclinical research. Overall, this review aims to clarify FPR2's role in inflammation and provide insights for the development of new drugs against inflammatory diseases.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polypharmacology: new drugs in 2023-2024.","authors":"Piotr Ryszkiewicz, Barbara Malinowska, Eberhard Schlicker","doi":"10.1007/s43440-025-00715-8","DOIUrl":"https://doi.org/10.1007/s43440-025-00715-8","url":null,"abstract":"<p><p>Polypharmacology is an emerging approach to drug design and development that involves the use of multi-target-directed ligands (MTDLs), agents capable of interacting with multiple biological targets simultaneously. The effective treatment of chronic and multifactorial conditions, driven by the dysregulation of multiple interconnected pathways, such as cancer, autoimmune and metabolic disorders, cardiovascular and neurodegenerative diseases, is one of the most substantial challenges in contemporary pharmacology. 'Traditional' single-target-based treatment frequently shows limited effectiveness, as resistance to therapy develops or relapses occur. The rational use of MTDLs seems therefore a promising way to address the complexity of biological systems, feedback mechanisms, crosstalk, and molecular pathways. Many MTDLs have been successfully marketed to date. Moreover, plenty of them offer an additional benefit in comparison to 'traditional' treatment approaches. To assess whether the polypharmacological trend remains prevalent, we thoroughly analysed drugs approved in the years of 2023-2024 in Germany. Among 73 newly introduced substances, 18 are in line with the polypharmacology concept, including 10 antitumor agents, 5 drugs indicated for autoimmune disorders, 1 indicated for hand eczema, 1 antidiabetic (and anti-obesity) drug, and 1 modified corticosteroid.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atorvastatin attenuates the expression of damage-associated molecular patterns and inflammatory cytokines in patients with psoriasis.","authors":"Kalliopi Armyra, Amin M Ektesabi, James N Tsoporis, Shehla Izhar, Andreas S Triantafyllis, Howard Leong-Poi, Thomas G Parker, Alexandros C Katoulis, Loukianos S Rallidis, Panagiotis G Stavropoulos, Christina Antoniou, Claudia C Dos Santos, Ioannis Rizos","doi":"10.1007/s43440-025-00710-z","DOIUrl":"https://doi.org/10.1007/s43440-025-00710-z","url":null,"abstract":"<p><strong>Background: </strong>In psoriasis, damage-associated molecular patterns (DAMPs) released by damaged local tissue act as danger signals and trigger inflammatory responses. Statins, in addition to cholesterol-lowering, have anti-inflammatory effects. We sought to assess the effectiveness of atorvastatin in attenuating plasma DAMPs and inflammatory cytokines in adults with psoriasis.</p><p><strong>Methods: </strong>In this prospective 3-month study, we included 21 eligible psoriatic patients who received oral atorvastatin 10 mg/day and 14 non-psoriatic controls. Blood samples for DAMPs measurement were collected at baseline and 3 months. Additionally, efficacy outcomes were estimated using psoriasis severity index and dermatology-specific quality of life index scores at baseline and 3 months.</p><p><strong>Results: </strong>Compared to control, psoriatic plasma showed a decrease in the decoy of DAMPs, the soluble (s) receptor for advanced glycation end products (sRAGE), and increases in the DAMPs S100B, S100A7, S1100A12, S100A8/A9, DJ-1, the inflammatory cytokines IL-6, IL-1β and TNF-α. Atorvastatin for 3 months improved efficacy scores, increased sRAGE, and decreased DAMPs and inflammatory cytokines toward control levels. Mechanistically, in the immortalized embryonic fibroblast Swiss mouse cell line NIH3T3s, S100A12, and S100A7 induced an inflammatory response and atorvastatin increased sRAGE in the medium.</p><p><strong>Conclusion: </strong>Statin therapy is effective in lowering DAMPs-induced inflammation in psoriasis patients. The main limitation of our study is the small sample size, and the findings should be confirmed in a larger cohort.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic liability for anxiety and treatment response to the monoamine stabilizer OSU6162 in alcohol dependence: a retrospective secondary analysis.","authors":"Mun-Gwan Hong, Lotfi Khemiri, Joar Guterstam, Johan Franck, Nitya Jayaram-Lindström, Philippe A Melas","doi":"10.1007/s43440-025-00707-8","DOIUrl":"https://doi.org/10.1007/s43440-025-00707-8","url":null,"abstract":"<p><strong>Background: </strong>OSU6162, a monoamine stabilizer, has demonstrated efficacy in reducing alcohol and anxiety-related behaviors in preclinical settings. In a previous randomized, double-blind, placebo-controlled trial involving patients with alcohol dependence (AD), OSU6162 significantly reduced craving for alcohol but did not alter drinking behaviors. This retrospective secondary analysis explores whether genetic predispositions related to AD and associated traits might influence the response to OSU6162 treatment in original trial participants.</p><p><strong>Methods: </strong>Polygenic risk scores (PRSs) were calculated for 48 AD patients using PRSice-2 and genome-wide association study (GWAS) data for (i) alcohol use disorder and alcohol consumption, (ii) problematic alcohol use, (iii) drinks per week, (iv) major depression, and (v) anxiety (case-control comparisons and quantitative anxiety factor scores). Linear regression analyses, adjusted for population stratification, assessed interaction effects between PRSs and treatment type (OSU6162 or placebo) on various clinical outcomes.</p><p><strong>Results: </strong>Significant interactions were found between treatment type and anxiety factor score PRS at the genome-wide significance threshold. In the OSU6162-treated group, a higher anxiety PRS was associated with reductions in the number of drinks consumed (FDR = 0.0017), percentage of heavy drinking days (FDR = 0.0060), and percentage of drinking days (FDR = 0.0017), with a trend toward reduced blood phosphatidylethanol (PEth) levels (FDR = 0.068). These associations were absent in the placebo group.</p><p><strong>Conclusions: </strong>These preliminary findings suggest that anxiety PRS may help predict response to OSU6162 treatment in AD. Further research with larger cohorts and more comprehensive genetic data is needed to confirm these results and advance personalized medicine approaches for alcohol use disorder.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating whether alcohol is transformed to norepinephrine or dopamine in the mouse brain.","authors":"Piotr Wlaź, Paul J Fitzgerald, Paweł Żmudzki, Katarzyna Socała","doi":"10.1007/s43440-025-00708-7","DOIUrl":"https://doi.org/10.1007/s43440-025-00708-7","url":null,"abstract":"<p><strong>Background: </strong>A number of rodent studies have investigated the effects of alcohol (ethanol) administration on the catecholaminergic neurotransmitters, norepinephrine (NE) and dopamine (DA). These studies suggest that presentation of alcohol to mice or rats can alter brain levels of NE and DA, in various subregions. Other studies have presented the hypothesis that there may be an unidentified pathway in rodents, and other organisms, that actually transforms ethanol to NE or DA. Here, this paper investigates the hypothesis in male CD-1 mice.</p><p><strong>Methods: </strong>Experimental mice were systemically injected with an intoxicating dose of stable isotope-labeled carbon 13 (C13) ethanol (ethanol-1-¹³C, 20% v/v, 1.5 g/kg, ip), and brain samples (hippocampus and brainstem) were collected two hours post-injection. Two other groups of mice received normal unlabeled carbon 12 (C12) ethanol or a water (Control) injection, respectively.</p><p><strong>Results: </strong>Although we had difficulty detecting the two neurotransmitters (especially C13 NE) due to their very low concentrations, high-resolution mass spectrometry analysis suggests that C12 ethanol selectively boosted hippocampal C12 NE, and C13 ethanol likewise boosted hippocampal C13 NE. We did not observe effects on DA.</p><p><strong>Conclusions: </strong>These data provide preliminary information on whether there is a novel biosynthetic pathway in mice that converts alcohol to catecholamines in select brain regions, where the ethanol molecule would presumably help form the ethanolamine side chain of NE. There are, however, alternative interpretations of these findings, including that acute alcohol administration modulates catecholamine release, reuptake, metabolism, or canonical biosynthesis.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carvacrol in asthma management: a comprehensive review of its therapeutic potential and mechanisms of action.","authors":"Deepa Neopane, Poonam Kushwaha","doi":"10.1007/s43440-025-00709-6","DOIUrl":"https://doi.org/10.1007/s43440-025-00709-6","url":null,"abstract":"<p><p>Asthma, a chronic inflammatory disorder of the airways, remains a significant global health concern. Current treatments focus on symptom management and inflammation control, but the search for more effective and safer therapies continues. Carvacrol, a naturally occurring monoterpenoid phenol found in essential oils of various plants, has emerged as a promising bioactive compound with potent anti-inflammatory, antioxidant, and bronchodilatory properties. This review explores the potential of carvacrol as a novel therapeutic agent for asthma management. We discuss its mechanisms of action, including modulation of inflammatory pathways, inhibition of oxidative stress, and relaxation of bronchial muscles. Additionally, preclinical and clinical studies evaluating the efficacy and safety of carvacrol in asthma treatment are analyzed. The integration of carvacrol into existing treatment regimens could offer a multifaceted approach to asthma management, enhancing therapeutic outcomes and improving patients' quality of life.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compound PZ-1262, a 4-isoquinoline-sulfonamide analog of Brexpiprazole, produces potential antidepressant, anxiolytic and procognitive effects in rodent models.","authors":"Anna Partyka, Joanna Gołębiowska, Krzysztof Marciniec, Vittorio Canale, Wojciech Trybała, Grzegorza Satała, Katarzyna Grychowska, Magdalena Jastrzębska-Więsek, Andrzej J Bojarski, Agnieszka Nikiforuk, Władysława A Daniel, Anna Wesołowska, Paweł Zajdel, Piotr Popik","doi":"10.1007/s43440-025-00713-w","DOIUrl":"https://doi.org/10.1007/s43440-025-00713-w","url":null,"abstract":"<p><strong>Background: </strong>Novel antipsychotics are characterized by multitarget profile of action, affecting among others, dopamine and serotonin receptors. In a series of experiments, we designed, synthesized and examined two new isoquinoline-sulfonamide analogs of the modern multitarget antipsychotics aripiprazole and brexpiprazole, compounds PZ-1262 and PZ-1264. We hypothesized that the 4-isoquinolinesulfonamide moiety, derived from the structure of 5-HT₆ receptor antagonists, would provide compounds with enhanced activity at 5-HT₆ receptors, along with partial agonistic activity at 5-HT_1A and D₂ receptors.</p><p><strong>Methods: </strong>The receptor binding profile, functional activity, and metabolic stability of PZ-1262 and PZ-1264 were evaluated through in vitro assays. Potential antipsychotic, antidepressant, anxiolytic, and pro-cognitive effects were assessed using in vivo behavioral tests in rodents.</p><p><strong>Results: </strong>In vitro, PZ compounds demonstrated partial agonistic activity at 5-HT_1A receptor, antagonistic activity at D₂ and D₃ as well as 5-HT_2A, 5-HT₆ and 5-HT₇ receptors and metabolic stability. In vivo, both compounds enhanced phencyclidine-induced hyperactivity in rats and decreased immobility time in the forced swim test in mice, without influencing spontaneous locomotor activity. In the novel object recognition test in rats, they demonstrated pro-cognitive effects in phencyclidine disturbed conditions. PZ-1262 potentiated D-amphetamine-induced hyperactivity, exhibited anxiolytic-like effects in the four plates test in mice, and demonstrated significant brain penetration.</p><p><strong>Conclusions: </strong>The complex pharmacodynamic profile translated into the useful psychotropic effects. While the compounds potentiated D-amphetamine- and phencyclidine-induced hyperactivity, this action could be regarded as a desired activating effect rather than evidence against antipsychotic-like efficacy. Present findings point to PZ-1262 as a more promising lead compound for further research.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The metabolism of big endothelin-1 axis and lipids affects carotid atherosclerotic plaque stability - the possible opposite effects of treatment with statins and aspirin.","authors":"Adam Płoński, Anna Krupa, Dariusz Pawlak, Katarzyna Sokołowska, Beata Sieklucka, Marcin Gabriel, Adam Filip Płoński, Jerzy Głowiński, Krystyna Pawlak","doi":"10.1007/s43440-025-00714-9","DOIUrl":"https://doi.org/10.1007/s43440-025-00714-9","url":null,"abstract":"<p><strong>Background: </strong>The understanding of endothelin's role in carotid plaque instability is limited. We have studied the big endothelin-1 (ET-1) axis and its role in carotid plaque stability in patients undergoing carotid endarterectomy (CEA). The interactions of endothelins with known CVD risk factors were also evaluated.</p><p><strong>Methods: </strong>We studied 77 patients, who were divided into subgroups based on the optimal cut-off for grey-scale median (GSM), a marker of plaque instability. GSM values < 46.87 were designated as unstable carotid plaque, while GSM ≥ 46.87 were assigned to stable plaque. Twelve people without carotid atherosclerosis served as controls. Big ET-1, ET-1 and ET-1 (1-31) were measured and the endothelin-converting enzyme-1 (ECE-1) and chymase activity were calculated. Clinical and laboratory parameters were also evaluated.</p><p><strong>Results: </strong>ET-1 levels and ECE-1 activity were increased in all patient groups compared to controls (all P < 0.001) - and were higher in patients with unstable plaque than in those with stable plaque (P < 0.01). ET-1 (1-31) did not differ between the groups. ET-1 levels and ECE-1 activity inversely correlated with total cholesterol, LDL-cholesterol, and GSM values, whereas GSM was positively associated with total cholesterol and LDL fractions. Detailed analysis of patients according to the pharmacotherapy used revealed that statins favored ET-1 formation independently of cholesterol-lowering properties, whereas aspirin reduced this effect.</p><p><strong>Conclusions: </strong>ET-1 formation is the main pathway of big ET-1 metabolism in patients with carotid atherosclerosis, especially in those with plaque instability. Statins and aspirin appear to have opposing effects on ET-1 formation, suggesting the greater benefit related to plaque stability in patients taking both drugs concomitantly.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}