Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Attenuating amiodarone-induced lung toxicity by the vitamin D receptor activator paricalcitol in rats: targeting TLR4/NF-κB/HIF-1α and TGF-β/Smad signaling pathways.","authors":"Aamal G El-Waseif, Mahmoud Elshal, Dalia H El-Kashef, Nashwa M Abu-Elsaad","doi":"10.1007/s00210-025-04568-z","DOIUrl":"https://doi.org/10.1007/s00210-025-04568-z","url":null,"abstract":"<p><p>Amiodarone, an antiarrhythmic drug, has been reported to precipitate lung injury by various mechanisms. Vitamin D receptor (VDR) is extensively expressed in the lung, and the disrupted vitamin D/VDR axis may underlie various lung disorders. Therefore, the current study intended to explore the beneficial impact of paricalcitol, a VDR activator, on amiodarone-provoked lung injury and elucidate its possible involved molecular mechanisms. Male Wistar rats were intraperitoneally injected with paricalcitol (0.2 µg/kg) and orally administered amiodarone (40 mg/kg) once daily for four weeks. Our findings revealed that paricalcitol diminished BALF leucocyte count and total protein, serum LDH activity, and pulmonary histopathological changes and counteracted pulmonary oxidative stress. Moreover, paricalcitol decreased pulmonary toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB) p65, tumor necrosis factor alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1), and phosphorylated small mothers against decapentaplegic 3 (pSmad 3) levels in line with less lung fibrosis percentage. Interestingly, these results were accompanied by suppressed hypoxia-inducible factor-1α (HIF-1α) lung expression. Taken together, paricalcitol protected against amiodarone-induced lung damage in rats through antioxidant, anti-inflammatory, and antifibrotic activities.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286556","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":"Metabolomic and biochemical evaluation of linalool and methyl eugenol as natural alternatives to varenicline in nicotine-induced metabolic dysfunction.","authors":"Mahpara Gondal, Muhammad Sajid Hamid Akash, Shagufta Kamal, Kanwal Rehman","doi":"10.1007/s00210-025-04695-7","DOIUrl":"https://doi.org/10.1007/s00210-025-04695-7","url":null,"abstract":"<p><p>N icotine, the principal addictive compound in tobacco, exerts widespread metabolic toxicity, including oxidative stress, mitochondrial dysfunction, amino acid and lipid derangements, and inflammatory damage to vital organs. Despite the clinical use of varenicline tartrate (VT) as a smoking cessation drug, its therapeutic effects on nicotine-induced metabolic dysfunction remain underexplored. Plant-derived phytochemicals such as linalool (LL) and methyl eugenol (ME), known for their antioxidant and anti-inflammatory properties, may offer comparable or superior protective effects as compared to that of VT. This study is aimed at evaluating and comparing the therapeutic efficacy of LL and ME with VT in attenuating nicotine-induced metabolic, biochemical, and histopathological abnormalities using integrated GC-MS and ESI-MS/MS-based metabolomics. Biochemical markers (ALT, AST, IL-6, TNF-α, MDA); histopathological analysis of hepatic, renal, and pulmonary tissues; and plasma metabolomic profiling using GC-MS and ESI-MS/MS were assessed in nicotine-exposed rats treated with LL, ME, and/or VT. Nicotine exposure significantly increased ROS, inflammatory cytokines, and liver enzymes while disrupting amino acid (glutamate) and lipid (LPCs, carnitines) metabolism. Histologically, nicotine caused hepatocellular vacuolation, renal tubular damage, and pulmonary congestion. Both LL and ME significantly reduced oxidative stress and inflammation, normalized glutamate levels, and restored tissue integrity. LL showed superior hepatoprotective and glutamate-restoring effects, while ME more effectively downregulated COX-2 and TNF-α. VT, although effective in reducing inflammatory markers, showed limited ability to reverse glutamate depletion or normalize lipid metabolic profiles. Unlike ME and LL, VT provided moderate histological recovery but failed to fully ameliorate tissue damage. GC-MS highlighted lipid metabolite abnormalities (e.g., LPCs, fatty acids), whereas ESI-MS/MS revealed significant reductions in oleamide and glutamate, confirming broader metabolic disruption and the superior recovery effects in LL and ME groups compared to VT. LL and ME exhibited greater therapeutic potential than VT in restoring metabolic balance and protecting against nicotine-induced organ damage. The ability of ME and LL to correct both lipid and amino acid metabolism positions them as promising natural alternatives or adjuncts for managing nicotine-associated metabolic dysfunction.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280765","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":"Improving the efficacy and targeting of letrozole for the control of breast cancer: in vitro and in vivo studies.","authors":"Shahira F El Menshawe, Seif E Ahmed, Amr Gamal Fouad, Amira H Hassan","doi":"10.1007/s00210-025-04634-6","DOIUrl":"https://doi.org/10.1007/s00210-025-04634-6","url":null,"abstract":"<p><p>Letrozole (LTZ) is one of the most widely used treatments for breast cancer (BC). However, several issues can affect its effectiveness and bioavailability when administered orally, including low solubility and uncontrolled release. The primary aim of this study is to develop a hydrogel containing LTZ-loaded invasomes (LLI). This formulation is designed to enhance LTZ's sustainability, permeability, targeting, bioavailability, and efficacy as a potential treatment for BC. The optimized LLI formulation was established by evaluating various formulations using the Box-Behnken design, focusing on entrapment efficiency and particle size. The LLI hydrogel was created by combining this optimal formulation with 2% Carbopol and was characterized in vitro for viscosity, release kinetics, and permeation. The anti-cancer effects, targeting ability, and safety of the LLI hydrogel were assessed in vivo using the 7,12-dimethylbenz(a)anthracene-induced breast cancer rat model (DIBC). The selected LLI formulation contained 3% phospholipids, 2% ethanol, and 0.5% cineole. Compared to free LTZ, the LLI hydrogel improved LTZ sustainability and permeation by 61.58% and 3.55-fold, respectively. Additionally, the LLI hydrogel reduced tumor volume by 99.69% compared to the DIBC group. Moreover, the concentration of LTZ accumulated in the tumor was 9.36 times greater in the LLI hydrogel than in the oral LTZ group. The transdermal LLI hydrogel represents a promising and safe treatment option for BC.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280780","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":"Finn Waagstein and the paradigm shift in the treatment of heart failure with β-adrenergic receptor antagonists ('β-blockers').","authors":"Kristina Lorenz, Ursula Ravens","doi":"10.1007/s00210-025-04594-x","DOIUrl":"https://doi.org/10.1007/s00210-025-04594-x","url":null,"abstract":"<p><p>Beta-adrenergic receptor antagonists, formerly called 'β-blockers' (which name will be used throughout this historical review), were initially used for their antihypertensive, anti-ischemic, and antiarrhythmic effects. In the early 1970s, the Swedish cardiologist Finn Waagstein opposed the paradigm that β-blockers were contraindicated in patients with decompensated heart failure. This review retraces the exciting paths of Waagstein's personal fight for recognition of his successful therapy of cardiac decompensation in patients with acute myocardial infarction and also of heart failure. In the second part, we summarise the clinical trials that led to the slow acceptance by the scientific community of the paradigm shift from contraindication to first-line treatment with β-blockers in heart failure.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280817","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":"Association between vitamin D deficiency and depressive symptoms among shift workers: Insights from network pharmacology and bioinformatics studies.","authors":"Shrouq E Alrashidi, Wejdan F Alanazi, Obaid Afzal, Mubarak A Alamri","doi":"10.1007/s00210-025-04709-4","DOIUrl":"https://doi.org/10.1007/s00210-025-04709-4","url":null,"abstract":"<p><p>Vitamin D deficiency is soaring among shift workers due to multiple issues, including poor UVB experience. The objective of this study was to identify precise mechanisms by which vitamin D deficiency might aggravate depressive symptoms among shift workers. Shift work is also associated with disrupting circadian rhythm, leading to depressive symptoms. Differential expressed genes (DEGs) in depression patients (GSE80655, GSE169459, GSE217811, GSE190518, GSE98793, GSE23848, GSE76826, GSE101521, and GSE54572) and in shift workers (GSE122541) with controls were examined in the GEO database. Genes associated with vitamin D deficiency were gathered from the GenCard database. Overlapping core targets were collected by uploading genes into the Bioinformatics and Evolutionary Genomics database. STRING database was used to screen the PPI (protein-protein interaction) network of cross-targets. Cytoscape was used to select core targets and to set up the pathway-gene network. GO (Gene Ontology) enrichment and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway investigations were executed by the database ShinyGO. A molecular docking examination was performed to explain the interaction between protein targets and calcitriol (active form of vitamin D), and binding affinity was confirmed by a 100-ns molecular dynamics simulation study. Our finding designated that the deficit of vitamin D might be involved in the pathology of depression among shift workers mainly through activation of the inflammatory response via upregulation of TNF, IL-6, and IL-1β (pro-inflammatory markers).</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280815","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":"The SGLT2 inhibitor empagliflozin promotes increased fatty acid oxidation in skeletal muscle cells.","authors":"Stanislava Stevanovic, Parmeshwar B Katare, Hilde Mari Volledal, Hege G Bakke, Klemen Dolinar, Sergej Pirkmajer, D Margriet Ouwens, G Hege Thoresen, Eili T Kase, Arild C Rustan","doi":"10.1007/s00210-025-04670-2","DOIUrl":"https://doi.org/10.1007/s00210-025-04670-2","url":null,"abstract":"<p><p>In this study we investigated the potential for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMPA) to modify energy metabolism in human primary skeletal muscle cells and mouse C2C12 skeletal muscle cells. The results showed that treatment of human myotubes with EMPA for 96 h decreased oxidation of exogenously added glucose and acetoacetate measured as CO₂ production, whereas CO₂ production from exogenously added fatty acids and leucine was increased compared to control cells. Uptake of acetoacetate by the cells was decreased by EMPA. Moreover, there were no EMPA-induced changes in glucose, fatty acid or leucine uptake by human myotubes, neither was lactate concentration in cell culture medium changed after exposure to EMPA. Treatment with EMPA increased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in human myotubes, while there was no effect of EMPA in human myotubes on gene expression of selected metabolic genes. Real time cell metabolic analysis in C2C12 cells showed that EMPA reduced basal respiration and glycolysis, while under conditions promoting use of endogenous fatty acids, maximal respiration and ATP production was increased by EMPA. In summary, treatment of skeletal muscle cells in vitro with EMPA caused changes in energy metabolism promoting enhanced fatty acid and leucine catabolism, decreased metabolism of glucose and acetoacetate, and reduced glycolysis. The observed changes in energy metabolism may be related to AMPK activation.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280741","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":"Protective effect of thymoquinone against acrylamide-induced hepatotoxicity in the rat: role of MAPK and apoptosis pathways.","authors":"Shirin Ghasemian, Soghra Mehri, Jamshid Tabeshpour, Mohammad Reza Zirak, Fatemeh Nezhadhosein, Hossein Hosseinzadeh","doi":"10.1007/s00210-025-04686-8","DOIUrl":"https://doi.org/10.1007/s00210-025-04686-8","url":null,"abstract":"<p><p>Acrylamide (ACR) is widely used in industry and induces hepatotoxicity. Thymoquinone (TQ), the main constituent of the black seed (Nigella sativa L.) oil, possesses potent antioxidant and anti-apoptotic properties. The potential protective effect of TQ in ACR-induced hepatotoxicity through MAPK signaling and intrinsic/extrinsic apoptosis pathways was investigated. Animals were randomly divided into seven groups (n = 6). Control (normal saline), ACR (50 mg/kg), ACR + TQ (2.5, 5 and 10 mg/kg), ACR + vitamin E (200 mg/kg), and TQ (10 mg/kg) were administered intraperitoneally to male Wistar rats for 11 days. The content of malondialdehyde and glutathione in the liver, alanine aminotransferase, aspartate transaminase, albumin, and total serum protein were measured. Apoptosis- and mitogen-activated protein kinases (MAPK) pathway proteins in the liver were evaluated by western blotting. ACR increased AST (p < 0.001) and MDA (p < 0.01) levels and decreased GSH (p < 0.01) content in comparison to the control group. The levels of apoptosis pathway proteins (caspases 3, 8, and 9) and MAPK pathway proteins (p-p38, p-JNK, and JNK) were significantly increased in the ACR group. Co-administration of TQ (10 mg/kg) with ACR remarkably reduced AST (p < 0.01), enhanced GSH content (p < 0.001), reduced MDA level (p < 0.05), and down-regulated caspases 3, 8, and 9 (p < 0.05) and p-p38, p-JNK, and JNK proteins. ACR induces hepatotoxicity via oxidative stress and activation of MAPK and apoptosis pathways. TQ exerts a hepatoprotective effect through its antioxidant, anti-apoptotic, and MAPK-modulating properties.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275373","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":"Protective effect of trans-sodium crocetinate on nephrotoxicity induced by cisplatin: in vitro and in vivo models.","authors":"Danial Esmaeilzadeh, Mohammad Shariati Rad, Majid Keshavarzi, Homa Fazeli Kakhki, Hossein Hosseinzadeh, Abolfazl Khajavi Rad, Sakineh Amoueian, Bibi Marjan Razavi","doi":"10.1007/s00210-025-04633-7","DOIUrl":"https://doi.org/10.1007/s00210-025-04633-7","url":null,"abstract":"<p><p>Trans-sodium crocetinate (TSC), a novel derivative of crocetin, has demonstrated potential protective effects against oxidative stress and apoptosis. This study aims to investigate the protective effect of TSC against cisplatin-induced nephrotoxicity by evaluating both in vivo and in vitro models. In the in vivo model, rats were pretreated with TSC (2.5, 5, and 10 mg/kg) for 5 days. Cisplatin (20 mg/kg) was injected on the 5th day to induce nephrotoxicity followed by TSC administration for an additional 2 days. Blood urea nitrogen (BUN) and serum creatinine (sCr) levels were measured to assess kidney function. Histopathological examinations and assessment of oxidative stress were conducted to evaluate renal tissue injury. In the in vitro model, HEK-293 cells were treated with cisplatin (150 µM) both with and without TSC pretreatment. Cell viability, reactive oxygen species (ROS) production, and apoptosis were subsequently evaluated. TSC significantly reduced BUN and sCr levels in rats exposed to cisplatin. Histopathological analysis revealed a reduction in tubular necrosis and other pathological changes associated with cisplatin toxicity. TSC also decreased MDA levels and increased GSH content in renal tissue. In HEK-293 cells, TSC pretreatment enhanced cell viability, reduced ROS production, and suppressed apoptosis by decreasing the Bax/Bcl-2 ratio and the expression of caspase-3 protein. TSC effectively protects against cisplatin-induced nephrotoxicity and cytotoxicity by reducing oxidative stress and apoptosis. These findings highlight TSC's potential as a therapeutic agent to mitigate the nephrotoxic effects of cisplatin in clinical settings.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275376","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":"Polyphenol-based therapeutics for glioblastoma: validation from In-vitro cell viability assay and integrated onco-omics computational analysis.","authors":"Yogesh H S, Sadik Shaik, Sibghatullah Muhammad Ali Sangi, Krishna Swaroop, Sreeharsha Nagaraja, Anitha K N, Vipin Kumar Mishra, Santosh Prasad Chaudhary Kurmi, Subrata Nath, Shankar Thapa","doi":"10.1007/s00210-025-04690-y","DOIUrl":"https://doi.org/10.1007/s00210-025-04690-y","url":null,"abstract":"<p><p>Glioblastoma (GBM) is one of the most aggressive brain tumors, with poor therapeutic outcomes due to its complex molecular profile. This study investigated the multi-target potential of three natural polyphenols-Ferulic acid, Morin, and Mangiferin-through an integrative computational strategy combining network pharmacology, onco-omics, molecular docking, molecular dynamics (MD) simulations, and density functional theory (DFT). Cross-referencing polyphenol-associated targets with GBM-related genes identified 13 common targets (e.g., PTGS2, EGFR, ESR1, MMP9). Protein-protein interaction analysis showed significant connectivity (p = 1.54 × 10⁻⁸), highlighting their relevance in GBM. Gene Ontology and KEGG enrichment revealed roles in proliferation, apoptosis, and migration, with enrichment in PI3K-Akt and MAPK signaling pathways. Molecular docking confirmed stable binding, with Mangiferin showing the strongest affinities: -11.0 kcal/mol (6ESM), -8.2 kcal/mol (5UGC), -7.5 kcal/mol (5UFW), and -9.1 kcal/mol (5IKT). MD simulations revealed the 5IKT-Mangiferin complex to be the most stable, with a favorable binding free energy (-32.0 ± 4.4 kcal/mol), while PCA and free energy landscapes supported reduced conformational variability. DFT results further supported favorable electronic properties. In vitro assays showed dose-dependent cytotoxicity, with IC₅₀ values of 9.43 µM (Morin), 4.65 µM (Mangiferin), and 6.22 µM (5-FU). Collectively, Mangiferin emerged as the lead candidate with superior binding stability and multi-target potential against GBM. This integrated framework provides mechanistic insights supporting polyphenol-based therapeutic development and warrants further in vivo validation.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275354","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":"Venous thromboembolism events associated with tofacitinib in rheumatoid arthritis patients: a real-world study from FAERS database.","authors":"Jintuo Zhou, Ruihong Cai, Peiguang Niu, Tingting Chen, Guimu Guo, Xiaoping Zeng, Jinhua Zhang","doi":"10.1007/s00210-025-04642-6","DOIUrl":"https://doi.org/10.1007/s00210-025-04642-6","url":null,"abstract":"<p><p>Tofacitinib, a Janus kinase (JAK) inhibitor approved in 2012, has become a pivotal oral treatment for rheumatoid arthritis (RA). However, the risk of venous thromboembolism (VTE) with tofacitinib in RA patients remains uncertain. This study aims to assess the association between tofacitinib use and the risk of VTE events in patients with RA using data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Additionally, this analysis sought to compare the reporting odds ratio (ROR) of VTE associated with tofacitinib and tumor necrosis factor inhibitors (TNFi). We conducted a retrospective pharmacovigilance study using FAERS data from the first quarter of 2012 to the fourth quarter of 2024. Disproportionality analysis was performed using ROR to evaluate the reporting risk of VTE events associated with tofacitinib compared with TNFi agents. A total of 1,786,456 adverse event reports related to RA were identified. Among these, 635 VTE events were associated with tofacitinib use and 1,354 VTE events were associated with TNFi agents. Tofacitinib was associated with a significantly elevated risk of VTE compared with the overall FAERS database (ROR 1.56, 95% CI 1.43-1.70) and with TNFi (ROR 2.20, 95% CI 2.00-2.40). Subgroup analysis revealed that the increased risk was particularly notable for pulmonary embolism (PE) (ROR 1.90, 95% CI 1.69-2.12) and deep vein thrombosis (DVT) (ROR 1.36, 95% CI 1.16-1.59). In this real-world study, tofacitinib use was associated with a higher reporting risk of VTE events compared with TNFi in RA patients. These findings underscore the need for careful patient selection and risk assessment when prescribing tofacitinib. Further prospective studies are warranted to confirm these associations and explore the underlying mechanisms.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275081","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}