European journal of pharmacology最新文献

{"title":"CircPDS5B knockdown attenuates sevoflurane-induced developmental neurotoxicity and associated intracellular alkalinization.","authors":"Yixing Lu, Xiaoling Nong, Fangfang Yang, Niqiao Chen, Zhijie Liang, Kaipeng Luo, Zhenquan Lu, Yunan Lin","doi":"10.1016/j.ejphar.2026.179448","DOIUrl":"https://doi.org/10.1016/j.ejphar.2026.179448","url":null,"abstract":"<p><p>Neonatal sevoflurane exposure can cause developmental neurotoxicity, but the molecular events linking anesthetic exposure to neuronal injury remain incompletely understood. We examined whether circPDS5B-associated disruption of intracellular acid-base homeostasis contributes to this injury. Primary hippocampal neurons and postnatal day 5 (P5) rats were exposed to 4.0% sevoflurane for 6 h. Cultured neurons were transduced with adenovirus on day 4 in vitro (DIV 4), and neonatal rats received bilateral microinjections of Ad-sh-circPDS5B into hippocampal CA1 at P3. In vitro, sevoflurane increased circPDS5B expression, reduced miR-92a-3p and carbonic anhydrase IX (CA9) levels, and induced intracellular alkalinization, reduced viability, and organelle ultrastructural abnormalities. Dual-luciferase assays supported a sequence-specific interaction between circPDS5B and miR-92a-3p. CircPDS5B knockdown increased miR-92a-3p and CA9 expression toward control levels, attenuated intracellular alkalinization, and was associated with less prominent mitochondrial and endoplasmic reticulum ultrastructural abnormalities. In vivo, circPDS5B knockdown attenuated the sevoflurane-associated reductions in hippocampal CA9 expression and CA1 dendritic spine density and was associated with improved subsequent behavioral performance in the Morris water maze and open-field test. These findings support an association between circPDS5B dysregulation, altered intracellular pH regulation, and sevoflurane-induced developmental neurotoxicity. The circPDS5B/miR-92a-3p/CA9 axis should be considered a candidate regulatory mechanism pending pathway-specific rescue experiments.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"179448"},"PeriodicalIF":5.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223585","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":"Amifostine attenuates pressure overload-induced cardiac hypertrophy and metabolic remodeling via the SIRT1/PPAR-α axis in rats.","authors":"Mohammad Shahbazian, Alireza Imani, Mahdieh Faghihi, Shadi Sadat Seyyed Ebrahimi, Mohammad Rahimi, Kamran Rakhshan","doi":"10.1016/j.ejphar.2026.179422","DOIUrl":"https://doi.org/10.1016/j.ejphar.2026.179422","url":null,"abstract":"<p><p>Pathological cardiac hypertrophy induced by chronic pressure overload is accompanied by significant metabolic disturbances, including impaired myocardial lipid metabolism. This study ascertained whether the cytoprotective agent amifostine (WR-2721) exerts cardioprotective effects along pressure overload-induced remodeling and whether these effects are linked to modulation of the SIRT1/PPAR-α axis. Male Wistar rats (n = 24) were assigned to Sham, abdominal aortic constriction (AAC), and AAC + amifostine (200 mg/kg, i.p., weekly for 8 weeks) groups, with amifostine administered concurrently with hypertrophic stress. The cardiac structure and function were appraised using echocardiography and histological analyses, with the expression of SIRT1, PPAR-α, and key regulators of lipid metabolism examined by Western blotting. Amifostine treatment was associated with attenuation of pressure overload-induced cardiac hypertrophy, reflected by lower heart and lung weight ratios, preservation of functional indices, and diminished myocardial fibrosis. At the molecular level, amifostine administration was accompanied by relative normalization of SIRT1 and PPAR-α expression, elevated levels of fatty acid oxidation-related proteins, and suppression of lipogenic markers. These findings suggest that amifostine mitigates pressure overload-induced cardiac remodeling and is associated with improved myocardial metabolic homeostasis, accompanied by favorable changes in the expression of SIRT1, PPAR-α, and lipid metabolism-related proteins. While these observations support the potential involvement of the SIRT1/PPAR-α signaling pathway, further mechanistic studies are required to establish its causal role in mediating the cardioprotective effects of amifostine.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"179422"},"PeriodicalIF":5.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215436","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":"Oxycodone self-administration induces microRNA and gene expression changes in the rat nucleus accumbens.","authors":"Maria Mavrikaki, Christos Miliotis, Dimitra Karagkouni, Lisa Maturin, Jane Banahan, Tanvi Saxena, Irais Valenzueala Arzeta, Sabrina Zhu, Ioannis S Vlachos, Olivier George, Elena Chartoff, Frank J Slack","doi":"10.1016/j.ejphar.2026.179412","DOIUrl":"https://doi.org/10.1016/j.ejphar.2026.179412","url":null,"abstract":"<p><p>Prescription opioid abuse remains a critical public health concern and is a major risk factor for the development of opioid use disorder (OUD). Thus, there is an urgent need to better understand the neurobiological mechanisms underlying OUD in order to develop therapeutics and address the ongoing opioid epidemic. In this study, we hypothesized that microRNAs regulate gene expression changes following oxycodone self-administration. To test our hypothesis, we utilized a long-access drug self-administration paradigm in rats. Briefly, adult male Sprague-Dawley rats were trained to self-administer oxycodone (0.15mg/kg/infusion) or saline and were sacrificed 24h (withdrawal) following the last self-administration session. Brains were collected and the nucleus accumbens (NAc) was extracted and was processed for small RNA and RNA sequencing. We found that oxycodone self-administration changed the expression of 40 genes and 16 mature microRNAs (miRNAs). Bioinformatic predictions revealed that opioid-regulated genes are predicted targets of differentially regulated miRNAs, suggesting that miRNAs contribute to opioid-mediated transcriptomic changes in the NAc. Furthermore, we validated some of these findings in an independent cohort of male and female rats and across different stages of the addiction cycle. We identified miRNAs that are dynamically regulated during oxycodone withdrawal, as well as others that exhibit sustained regulation across different stages of the addiction cycle. Taken together, our data show that miRNAs may contribute to opioid-regulated gene expression and point to the therapeutic potential of miRNAs for OUD.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"179412"},"PeriodicalIF":5.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215373","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":"Repurposing Entrectinib and Ibrutinib as MNK/eIF4E Pathway Modulators in Ovarian Cancer.","authors":"Azadeh Rasouli, Mohammad Hossein Ghahremani, Sajjad Gharaghani, Shokoofeh Ghiam, Abass Kebriaeezadeh, Seyed Shahriar Arab, Shima Aliebrahimi, Seyed Naser Ostad","doi":"10.1016/j.ejphar.2026.179438","DOIUrl":"https://doi.org/10.1016/j.ejphar.2026.179438","url":null,"abstract":"<p><p>The ERK/MNK/eIF4E signaling axis is critically involved in cap-dependent translation and significantly impacts survival and chemotherapy resistance in ovarian cancer. Clinical data indicate that elevated eIF4E expression is an independent prognostic marker for poor overall survival (HR=1.17, p=0.027). However, there has yet to be a systematic evaluation of FDA-approved agents for their efficacy as MNK/eIF4E inhibitors. In the present study, a total of 2,180 FDA-approved compounds were screened using a comprehensive approach integrating machine learning, molecular docking, molecular dynamics, and binding free energy analysis to identify potential MNK1 modulators. Ibrutinib and Entrectinib emerged as the most promising candidates, forming stable complexes with MNK1 and displaying favorable binding energies (Entrectinib: ΔG = -131.66 ± 2.05 kJ/mol; Ibrutinib: ΔG = -87.36 ± 2.04 kJ/mol). Notably, Ibrutinib, conventionally recognized as a BTK inhibitor, and Entrectinib, a tropomyosin receptor kinase inhibitor, exhibited previously unreported off-target interactions with MNK1/eIF4E, suggesting new therapeutic applications for both agents. In vitro validation was conducted using the A2780-s and A2780-cp cell lines, with A2780-cp selected for its elevated MNK/eIF4E activity. Niclosamide, identified as an MNK/eIF4E inhibitor, served as a positive control in this investigation. Both compounds significantly diminished cell viability, lowered the p-eIF4E/eIF4E ratio as determined via Western blot analysis, impaired clonogenic survival, and induced S-phase arrest in A2780-cp cells. This study represents the first examination of the roles of Entrectinib and Ibrutinib as modulators of MNK1/eIF4E in ovarian cancer, providing substantial functional evidence for their efficacy in modulating the MNK/eIF4E pathway with eIF4E Phosphorylation-Suppressing Activity.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"179438"},"PeriodicalIF":5.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215167","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":"Tryptophan Metabolism in Heart Failure: Mechanisms, Biomarker Potential, and Therapeutic Implications.","authors":"Pingge He, Hongbo Chang, Hong Wu, Qiujia Kang, Shaoang Wang, Lei Xu, Zhentao Wang","doi":"10.1016/j.ejphar.2026.179440","DOIUrl":"https://doi.org/10.1016/j.ejphar.2026.179440","url":null,"abstract":"<p><p>Heart failure (HF) is a complex clinical syndrome characterized by progressive cardiac remodeling, metabolic dysregulation, and high morbidity and mortality worldwide. Emerging evidence suggests that metabolic reprogramming plays a central role in HF progression, among which tryptophan (TRP) metabolism has attracted increasing attention due to its involvement in inflammation, immune regulation, oxidative stress, mitochondrial dysfunction, and gut microbiota imbalance. TRP is mainly metabolized through the kynurenine pathway (KP), serotonin pathway, and gut microbiota-derived indole pathway, generating a series of bioactive metabolites with distinct cardiovascular effects. Recent studies have demonstrated that abnormal activation of the indoleamine 2,3-dioxygenase (IDO)-driven KP contributes to HF progression by promoting inflammatory activation, oxidative stress, myocardial fibrosis, and ventricular remodeling. In parallel, gut microbiota-derived TRP metabolites participate in the gut-heart axis and influence mitochondrial function, immune homeostasis, and cardiometabolic remodeling. In addition, TRP-related metabolites, particularly kynurenine (KYN) and the kynurenine-to-tryptophan ratio (KTR), exhibit promising potential as biomarkers for HF severity assessment and prognostic stratification. This review systematically summarizes the activation characteristics of TRP metabolic pathways in HF and discusses their mechanistic involvement in inflammation, immune regulation, gut microbiota dysbiosis, myocardial injury, oxidative stress, and mitochondrial dysfunction. Furthermore, emerging therapeutic strategies targeting TRP metabolism are highlighted, including pharmacological modulation, microbiota-targeted interventions, exogenous metabolite supplementation, and exercise-based metabolic regulation. Collectively, TRP metabolism represents a promising metabolic hub integrating immune, inflammatory, and mitochondrial signaling networks in HF and may provide novel opportunities for precision diagnosis and targeted therapy.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"179440"},"PeriodicalIF":5.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215224","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":"Isorhapontigenin alleviates sepsis-induced acute lung injury by targeting the RAF1-ERK1/2-CXCL10 axis to inhibit CXCR3⁺ neutrophil recruitment.","authors":"Ao-Lin Jiang, Chang Sun, Dong-Rong Luo, Yu-Ying Liang, Zheng Qin, Wan-Ying Zhang, Ze-Hui Jiang, Meng-Ru Wang, Hai-Hua Luo, Bing-Wen Zhu, Yi-Bai Qu, Lei Li, Yong Jiang","doi":"10.1016/j.ejphar.2026.179443","DOIUrl":"https://doi.org/10.1016/j.ejphar.2026.179443","url":null,"abstract":"<p><p>Sepsis is a life-threatening organ dysfunction syndrome resulting from a dysregulated host response to infection and is characterized by persistent hyperinflammation followed by immunosuppression. Isorhapontigenin (ISO), a natural stilbene derivative found in Chinese herbs and grapes, possesses potent antioxidant and anti-inflammatory properties; however, its potential therapeutic role in sepsis remains unclear. In this study, we investigated the protective effects of ISO against sepsis-induced multi-organ injury and the underlying molecular mechanisms. Using a murine model of sepsis, we observed that ISO administration considerably suppressed the expression of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the tissues. Furthermore, ISO treatment markedly improved survival rates and attenuated pathological damage in the liver and lung. Transcriptomic profiling revealed that ISO confers protection by modulating inflammatory cascades and inhibiting chemokine-mediated immune cell migration. Notably, C-X-C motif chemokine ligand 10 (CXCL10) was identified as a key hub gene. Mechanistically, ISO directly binds to RAF proto-oncogene serine/threonine-protein kinase (RAF1) and inhibits the RAF1-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway, thereby downregulating CXCL10 expression and preventing excessive infiltration of C-X-C motif chemokine receptor 3-positive (CXCR3⁺) neutrophils into pulmonary tissue. In conclusion, our findings demonstrate that ISO mitigates sepsis-induced lung injury via the RAF1/ERK1/2/CXCL10 axis, providing a potential mechanistic basis for further investigation of ISO as a therapeutic candidate for sepsis.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"179443"},"PeriodicalIF":5.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206711","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":"Schinifoline attenuates atherosclerosis and modulates gut microbiota and bile acid metabolism in ApoE^-/- mice.","authors":"Qian Liu, Tianlan Xi, Yilin Wen, Limei Ma, Gang Zou, Weimin Yu, Zhiyi Yuan, Chao Yu","doi":"10.1016/j.ejphar.2026.179416","DOIUrl":"https://doi.org/10.1016/j.ejphar.2026.179416","url":null,"abstract":"<p><p>Atherosclerosis (AS) remains a major global health burden despite advances in lipid-lowering therapies. Zanthoxylum bungeanum Maxim (ZBM) has demonstrated anti-atherosclerotic potential; however, the role of its active component, schinifoline (SF), in atherosclerosis remains unclear. In this study, we evaluated the anti-atherosclerotic effects of SF in high-fat diet (HFD)-fed ApoE^-/- mice. SF treatment attenuated aortic plaque formation, improved serum lipid parameters, and decreased inflammatory responses. Integrated 16S rRNA sequencing and untargeted metabolomics revealed that high-dose SF partially restored HFD-associated alterations in gut microbiota composition, including normalization of the Firmicutes/Bacteroidota ratio and changes in several atherosclerosis-associated genera, and altered bile acid profiles. In addition, SF reduced intestinal apical sodium-dependent bile acid transporter (ASBT) expression, suggesting a potential role in bile acid homeostasis. Collectively, these findings indicate that SF attenuates atherosclerosis and is associated with alterations in gut microbiota, bile acid profiles, and lipid and inflammatory responses, providing insights into its pharmacological effects.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"179416"},"PeriodicalIF":5.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206692","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":"Thymoquinone alleviates DSS-induced colitis in mice by protecting the intestinal mucosal barrier through inhibition of the Notch signalling pathway.","authors":"Tong Sun, Qiang Tang, Linxia Xu, Wei Liu, Fei Chen, Xiaoling Zhang, Zhi Ren, Zhenzeng Ma, Hailun Zheng, Dapeng Li, Qiangwu Wang, Xiquan Ke","doi":"10.1016/j.ejphar.2026.179405","DOIUrl":"https://doi.org/10.1016/j.ejphar.2026.179405","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the therapeutic effects and potential molecular mechanisms of the natural plant monomer thymoquinone (TQ) on colitis in mice. Particular attention was paid to protecting intestinal barrier integrity, apoptosis, and inflammatory responses.</p><p><strong>Methods: </strong>Colitis was induced in mice using 3% Dextran Sulfate Sodium (DSS). Concurrently, TQ (20 and 80 mg/kg) was administered intragastrically from days 1 to 7. The development of colitis and intestinal barrier integrity were assessed by monitoring body weight, Disease Activity Index (DAI) score, colonic length changes, pathological alterations, inflammatory cytokines, and the expression of relevant proteins. Caco-2 cells were stimulated in vitro with 100 ng/ml TNF-α to validate the regulatory effects of TQ on the Notch signaling pathway and tight junction proteins.</p><p><strong>Results: </strong>TQ significantly alleviates DSS-induced histopathological damage in mouse colon tissue, lowering the DAI. It reduces levels of pro-inflammatory cytokines (TNF-α, IL-1β) in peripheral serum, increases levels of the anti-inflammatory factor IL-10, and upregulates expression of intestinal barrier proteins (ZO-1, Occludin, MUC2). Furthermore, TQ upregulated Bcl-2, downregulated Bax, inhibited the activation of Cleaved Caspase-3, and reduced the apoptosis of mouse colonic epithelial cells. Mechanistically, TQ suppressed the excessive activation of the Notch signaling pathway, which is consistent with the results of the in vitro experiments.</p><p><strong>Conclusion: </strong>TQ significantly alleviated the clinical manifestations and pathological damage in DSS-induced colitis in mice, protected the integrity of intestinal epithelial cells, and reduced apoptosis, demonstrating its potential as a novel therapeutic agent for inflammatory bowel disease (IBD).</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"179405"},"PeriodicalIF":5.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192248","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":"Calcium-sensing receptor-NLRP3 inflammasome signaling in cardiovascular diseases: Preclinical evidence and translational perspectives.","authors":"Satnam Singh Mehadwan, Gauri Chaturvedi, Nandini Dubey, Pranav Panchbhai, Prabhakar Singh, Neeraj Parakh, Raj Kanwar Yadav, Harlokesh Narayan Yadav","doi":"10.1016/j.ejphar.2026.179436","DOIUrl":"10.1016/j.ejphar.2026.179436","url":null,"abstract":"<p><p>The chronic low-grade inflammation driven by NLR family pyrin domain containing 3 (NLRP3) inflammasome is increasingly acknowledged as an underlying mechanism of myocardial infarction, heart failure, atrial fibrillation, hypertension, and atherosclerosis. Extracellular Ca²⁺, amino acids, and other ligands link to intracellular Ca²⁺ overload, mitochondrial dysfunction, reactive oxygen species generation, thioredoxin-interacting protein activation, and NF-κB-dependent inflammasome priming via the calcium-sensing receptor (CaSR). Experimental studies indicate that CaSR may activate the NLRP3 inflammasome through these pathways in a cell- and context-dependent manner. In preclinical cardiovascular models, CaSR-mediated NLRP3 signaling has been implicated in neutrophil- and macrophage-mediated post-MI remodeling, atrial cardiomyocyte inflammatory remodeling in atrial fibrillation, and vascular smooth muscle and endothelial dysfunction in hypertension and atherosclerosis. Importantly, CaSR signalling may exert pro-inflammatory or protective effects depending on the cell type, ligand, dose, disease stage, and local microenvironment. Here, we review preclinical evidence and emerging translational evidence separately, highlighting the CaSR-NLRP3 signalling in cardiovascular disease, describe pharmacologic approaches that may modulate CaSR, NLRP3, or downstream inflammatory pathways, and identify key mechanistic and clinical knowledge gaps. Although direct clinical evidence for a complete CaSR-NLRP3 axis in cardiovascular diseases remains limited, these findings support further investigation of context-specific CaSR-NLRP3 crosstalk as a potential therapeutic target.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"179436"},"PeriodicalIF":5.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192214","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":"N-acetylcysteine inhibits gene and protein expression of MUC5AC in COPD-relevant human models: evidence from a meta-analysis.","authors":"Luigino Calzetta, Shima Gholamalishahi, Gian Marco Manzetti, Elena Pistocchini, Paola Rogliani","doi":"10.1016/j.ejphar.2026.179437","DOIUrl":"https://doi.org/10.1016/j.ejphar.2026.179437","url":null,"abstract":"<p><p>Chronic mucus hypersecretion is highly prevalent in chronic obstructive pulmonary disease and is associated with worse outcomes. MUC5AC is a key inducible gel-forming mucin driving pathological mucus overproduction. N-acetylcysteine (NAC) is widely used as a mucolytic and exhibits antioxidant and anti-inflammatory properties. Its quantitative impact on MUC5AC regulation has not been formally synthesized. We performed a systematic review and meta-analysis (OSF registration ID: 2vym4) of original studies evaluating the effect of NAC on MUC5AC gene and protein expression in human respiratory cell models of mucus hypersecretion. Standardized mean differences with 95% CIs were pooled using DerSimonian-Laird random-effects models. Heterogeneity, publication bias, sensitivity analyses, and random-effects meta-regression on NAC dose were conducted. Fifteen articles were included. NAC significantly reduced MUC5AC mRNA (standardized mean difference -1.30, 95% CI: -1.61 to -0.98; I²=37.07%), without significant dose-response. NAC produced very large reductions in extracellular (-2.70, 95% CI: -3.29 to -2.11; I²=48.89%) and intracellular (-2.38, 95% CI: -3.27 to -1.48; I²=67.35%) MUC5AC protein, with significant dose-response relationships for both. After sensitivity analyses, the pooled protein effect remained very large (-2.00, 95% CI: -2.38 to -1.62; I²=25.63%). Funnel plots and Egger's tests suggested publication bias, which diminished after exclusion of influential comparisons. NAC robustly inhibits MUC5AC gene and protein expression in human pre-clinical models of mucus hypersecretion, supporting a strong mucoregulatory action that complements mucolytic and antioxidant effects. These data reinforce the rationale for NAC use in chronic obstructive pulmonary disease patients with a hypersecretory phenotype.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"179437"},"PeriodicalIF":5.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178725","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}