Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Dihydroflavonoids outperform their flavonoid counterparts in lipid-lowering efficacy based on pairwise analyses.","authors":"Lie Yuan, Yazhen Zhang, Ao Zhang, Dongmei Chen, Xiandeng Li, Yuheng Wang, Long Chu, Xiaoli Li, Xiao Zhang, Qinjian Zhao","doi":"10.1007/s00210-026-05969-4","DOIUrl":"https://doi.org/10.1007/s00210-026-05969-4","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting approximately 25% of the adult population, yet no approved pharmacotherapy is currently available. Flavonoids have shown promise in improving MASLD, but the structural determinants underlying their lipid-lowering activities remain unclear. This study aimed to systematically investigate whether the presence or absence of the C-2,3 double bond affects the efficacy of flavonoids in ameliorating MASLD. Two pairs of C-2,3 positional isomeric flavonoids-eriodictyol (Compound 1a, dihydro form, C-2,3 single bond)/luteolin (Compound 1b, non-dihydro form, C-2,3 double bond) and dihydromyricetin (Compound 2a, dihydro form, C-2,3 single bond)/myricetin (Compound 2b, non-dihydro form, C-2,3 double bond)-were compared using an FFA-induced HepG2 cell model and an HFD-induced MASLD mouse model. Lipid accumulation, gene expression, target protein thermal stabilization (via CETSA), and compound-target interactions (via molecular docking) were systematically assessed. Both in vitro and in vivo experiments consistently demonstrated that the dihydro forms (C-2,3 single bond) exhibited superior efficacy to their non-dihydro counterparts (C-2,3 double bond) in reducing lipid accumulation and modulating lipid metabolism-related genes. Mechanistically, the dihydro forms showed broader regulatory effects on genes involved in fatty acid oxidation, de novo lipogenesis, and fatty acid uptake. CETSA and molecular docking analyses further suggested that the dihydro forms exhibited greater thermal stabilization of the target proteins and generally lower predicted binding energies across all three targets (PPARγ, ACC1, and FASN). This study provides the first systematic evidence that the C-2,3 single-bond configuration may represent a structural feature associated with enhanced lipid-lowering activity of flavonoids, offering experimental evidence for dietary intervention strategies and flavonoid-based lead compound optimization in MASLD.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137812","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":"Berberine inhibits gastric cancer progression by targeting canonical Wnt/β-catenin signaling in AGS cells.","authors":"Li Xiao, Ren Hui, Bai Jing","doi":"10.1007/s00210-026-05955-w","DOIUrl":"https://doi.org/10.1007/s00210-026-05955-w","url":null,"abstract":"<p><p>Gastric cancer (GC) progression is strongly associated with dysregulated proliferation, apoptosis resistance, epithelial-mesenchymal transition, invasion, and aberrant Wnt/β-catenin signaling. Berberine has shown anti-cancer activity in several tumor models; however, its mechanistic effects on Wnt/β-catenin-driven GC phenotypes require further clarification. This study investigated whether berberine suppresses AGS GC cell progression through inhibition of canonical Wnt/β-catenin signaling. AGS cells were treated with berberine at low, medium, and high concentrations, with CHIR99021 used for Wnt/β-catenin pathway activation and XAV939 as a pathway inhibitory control. Cell viability, proliferation, colony formation, cell cycle distribution, apoptosis, migration, invasion, EMT marker expression, β-catenin localization, TOP/FOP luciferase activity, ROS/RNS production, mitochondrial membrane potential, and glucose uptake were assessed using functional, molecular, and fluorescence-based assays. CTNNB1 knockdown was used to validate β-catenin-dependent mechanisms. Berberine reduced AGS cell viability, EdU incorporation, clonogenic survival, migration, invasion, and glucose uptake while inducing G0/G1 arrest, mitochondrial depolarization, oxidative/nitrosative stress, caspase activation, and apoptosis. Berberine increased E-cadherin and decreased N-cadherin, Vimentin, Snail, Slug, ZEB1, and MMP9, indicating suppression of EMT. Mechanistically, berberine reduced β-catenin expression, nuclear localization, TOP/FOP transcriptional activity, and downstream Wnt targets including CCND1, MYC, BIRC5, AXIN2, and MMP9. CHIR99021 partially reversed berberine-induced anti-tumor effects, whereas XAV939 and CTNNB1 knockdown mimicked or enhanced berberine activity. Berberine suppresses AGS GC cell progression by inhibiting canonical Wnt/β-catenin signaling, thereby reducing proliferation, EMT, invasion, metabolic activity, and survival while promoting cell cycle arrest and apoptosis.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137832","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":"Formononetin attenuates ethanol-induced gastric ulcer injury by targeting ALDH2 to inhibit oxidative stress.","authors":"Zhihong Liu, Xinjie Yao, Tingting Zhao, Yunhui Wang","doi":"10.1007/s00210-026-05942-1","DOIUrl":"https://doi.org/10.1007/s00210-026-05942-1","url":null,"abstract":"<p><p>Ethanol-induced gastric ulceration is primarily driven by oxidative stress, mitochondrial dysfunction, and gastric epithelial cell injury. Although formononetin (Fmn), a naturally occurring isoflavone, possesses well-documented antioxidant and anti-inflammatory properties, its protective role and underlying molecular mechanisms in ethanol-induced gastric injury remain unclear. In this study, ethanol-treated GES-1 gastric epithelial cells were used as an in vitro model to investigate the cytoprotective effects of Fmn. Cell proliferation, apoptosis, oxidative stress, and mitochondrial function were evaluated using biochemical and cellular assays. Potential molecular targets were identified through SwissTargetPrediction and molecular docking, followed by experimental validation, including ALDH2 knockdown, qRT-PCR, and enzymatic activity assays. Fmn significantly attenuated ethanol-induced cellular injury by restoring cell proliferation, suppressing apoptosis, reducing intracellular and mitochondrial reactive oxygen species, decreasing malondialdehyde levels, and enhancing superoxide dismutase activity. Molecular docking demonstrated a strong binding affinity between Fmn and aldehyde dehydrogenase 2 (ALDH2), which was further confirmed by increased ALDH2 mRNA and protein expression as well as enhanced enzymatic activity following Fmn treatment. Functional studies revealed that ALDH2 upregulation plays a pivotal role in preserving mitochondrial integrity and limiting oxidative damage. Collectively, these findings demonstrate that Fmn protects gastric epithelial cells against ethanol-induced injury through ALDH2-mediated suppression of oxidative stress and mitochondrial dysfunction, highlighting its potential as a promising therapeutic candidate for the prevention and treatment of alcohol-induced gastric ulceration.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127649","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":"Potential targets and mechanisms of Di(2-ethylhexyl) phthalate exposure in inducing chronic kidney disease: a multimodal study integrating epidemiology, network toxicology, and Mendelian randomization.","authors":"Yihan Wang, Qi Liu, Xiaojun Li, Ruizhi Tan, Hong Li, Junming Fan, Jun Zhu, Li Wang","doi":"10.1007/s00210-026-05972-9","DOIUrl":"https://doi.org/10.1007/s00210-026-05972-9","url":null,"abstract":"<p><p>Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer present in numerous consumer and medical products and has been associated with adverse effects in multiple organ systems, including the kidney. Chronic kidney disease (CKD) is an increasing global health burden, yet the molecular targets potentially linking DEHP exposure to CKD remain incompletely understood. This study integrated epidemiological analysis, network toxicology, Mendelian randomization (MR), molecular docking, and molecular dynamics simulations to investigate potential molecular targets associated with DEHP exposure and CKD. Data from the National Health and Nutrition Examination Survey (NHANES) were used to examine the association between urinary DEHP metabolites and CKD. DEHP-related and CKD-related targets were subsequently integrated to identify shared targets, followed by PPI network analysis and expression-based evaluation to prioritize candidate genes. MR analysis was then performed to assess the association between genetically proxied candidate genes and CKD. Molecular docking was used to explore the potential interactions between DEHP and the prioritized proteins, and molecular dynamics simulations were performed to further evaluate the structural stability of the predicted DEHP-CTSK complex. Higher urinary DEHP metabolite levels were associated with a higher prevalence of CKD. Four candidate genes-CTSK, ABL1, BCL2L1, and CCND1-were prioritized based on network and expression-based analyses. Among these genes, genetically proxied CTSK showed a significant positive association with CKD in the primary MR analysis. Molecular docking showed favorable predicted docking scores for DEHP with the four candidate proteins, while molecular dynamics simulations supported the structural stability of the predicted DEHP-CTSK complex over 100 ns. These findings provide convergent epidemiological, genetic, and computational evidence supporting CTSK as a candidate molecular target for further investigation in the context of DEHP-associated renal injury.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137757","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":"RVG29-functionalized nanocarriers for brain-targeted therapy of neurodegenerative diseases: mechanisms, therapeutic advances, and translational perspectives.","authors":"Sonam M Gandhi, Saraswati Patel, Nitin G Haswani, Shadma Wahab, Zia-Ul- Sabah, Devesh U Kapoor","doi":"10.1007/s00210-026-05958-7","DOIUrl":"https://doi.org/10.1007/s00210-026-05958-7","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDs) affect more than 55 million people worldwide, with this number projected to exceed 139 million by 2050 due to population aging. Alzheimer's disease (AD) accounts for 60-70% of dementia cases, while Parkinson's disease (PD) affects over 10 million individuals globally, highlighting the growing clinical and socioeconomic burden of these progressive neurological disorders. Effective treatment of AD, PD, amyotrophic lateral sclerosis (ALS), and related central nervous system disorders remains hindered by the blood-brain barrier (BBB), poor brain accumulation, rapid systemic clearance, and off-target toxicity. RVG29, a 29-amino-acid peptide derived from rabies virus glycoprotein, has emerged as a promising brain-targeting ligand because of its high affinity for nicotinic acetylcholine receptors expressed on neuronal and brain endothelial cells. This review critically examines the mechanisms underlying RVG29-mediated receptor-dependent BBB transcytosis, intracellular trafficking, and neuronal uptake. Furthermore, it comprehensively evaluates RVG29-functionalized lipid nanoparticles, polymeric nanoparticles, exosomes, biomimetic nanocarriers, micelles, inorganic nanostructures, and hybrid systems with respect to their physicochemical characteristics, targeting efficiency, therapeutic efficacy, and safety. Collectively, these nanocarriers demonstrate enhanced BBB penetration, increased drug accumulation in diseased brain regions, and efficient delivery of small molecules, genes, mRNA, and siRNA. By modulating oxidative stress, neuroinflammation, protein aggregation, ferroptosis, and mitochondrial dysfunction, RVG29-engineered nanocarriers provide significant neuroprotection with favorable biocompatibility and minimal immunogenicity. Despite these advances, challenges related to large-scale manufacturing, peptide stability, regulatory approval, and long-term biosafety must be addressed to facilitate their clinical translation as precision neurotherapeutics.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127689","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":"Hydroxysafflor yellow A attenuates microcirculatory disturbance in MAFLD via the EGFR/MAPK1 pathway.","authors":"Qing Liu, Nan Ai, Rui Wang, Zhenbo Li, Yihan Liu, Lei Wu, Yuqin Zhao, Jing Yang","doi":"10.1007/s00210-026-05980-9","DOIUrl":"https://doi.org/10.1007/s00210-026-05980-9","url":null,"abstract":"<p><p>The incidence of metabolic-associated fatty liver disease (MAFLD) continues to rise, making it a leading cause of chronic liver disease worldwide. Its pathological progression is frequently accompanied by microcirculatory dysfunction. However, effective therapeutic interventions targeting this specific process remain limited. Hydroxysafflor yellow A (HSYA) is the primary active component of Carthamus tinctorius L. It exerts diverse pharmacological effects, including anti-inflammatory, antioxidant, and microcirculation-improving activities. However, the specific mechanisms by which HSYA regulates microcirculatory dysfunction in MAFLD have yet to be elucidated. In this study, a rat model of MAFLD was established using a methionine choline-deficient (MCD) diet to investigate the protective effects of HSYA and the underlying EGFR/MAPK1 signaling mechanism. The results showed that HSYA treatment significantly reduced serum levels of ALT, AST, TC, TG, and ET-1, while increasing NO levels. HSYA administration also expanded mesenteric microvascular diameter and accelerated blood flow velocity. Furthermore, HSYA alleviated hepatic steatosis and inflammatory injury. These effects were accompanied by the downregulation of EGFR, MAPK1, and VEGF expressions in the liver, thereby inhibiting the overactivation of the EGFR/MAPK1 pathway. In summary, HSYA effectively ameliorates hepatic injury and microcirculatory dysfunction in MAFLD rats. The underlying mechanism is associated with inhibiting the overactivation of the EGFR/MAPK1 signaling pathway and downregulating VEGF expression, which collectively restores the balance of microvascular structure and function. These findings provide experimental evidence for the therapeutic potential of HSYA in treating MAFLD-related microcirculatory disorders.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137755","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":"Agomelatine improves symptom severity and quality of life in diarrhea-predominant irritable bowel syndrome: insights from a randomized controlled clinical trial.","authors":"Seyed Saman Talebi, Davoud Ahmadimoghaddam, Mahtabalsadat Mirjalili, Amir Keshavarzi, Maryam Zamanirafe, Yasaman Taghavi, Salman Khazaei, Maryam Mehrpooya","doi":"10.1007/s00210-026-05975-6","DOIUrl":"https://doi.org/10.1007/s00210-026-05975-6","url":null,"abstract":"<p><p>Irritable bowel syndrome with diarrhea predominance (IBS-D) significantly impairs Quality of Life (QOL) and is often accompanied by psychological distress. Agomelatine, a melatonergic antidepressant, has shown promise in modulating gastrointestinal symptoms and mood disorders. This study aimed to evaluate the efficacy and safety of agomelatine in patients with IBS-D. In this 8-week, double-blind, randomized, placebo-controlled trial, 61 adults aged 18-65 years with IBS-D diagnosed by Rome IV criteria and confirmed normal colonic anatomy and labs were randomized to agomelatine (12.5 mg daily, titrated to 25 mg) or placebo. Baseline symptoms were recorded during a 1-week run-in using the Bristol Stool Form Scale (BSFS) and IBS Symptom Severity Score (IBS-SSS). Psychological status was assessed using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and Depression (HADS-D) subscales, and QOL by the IBS Quality of Life questionnaire (IBS-QOL). The primary outcome was change in total IBS-SSS from baseline to week 8. Secondary outcomes included changes in individual IBS-SSS domains, stool consistency, bowel movement frequency, symptom days (pain, diarrhea, urgency, bloating), HADS-A, HADS-D, and IBS-QOL scores. Safety was monitored via adverse events and treatment discontinuations. All randomized participants were included in the intention-to-treat analysis. Both groups showed significant within-group reductions in total IBS-SSS (p < 0.001). Agomelatine produced greater reductions in total IBS-SSS than placebo (between-group difference in mean change, - 24.80 points; p = 0.034), abdominal pain severity, and abdominal pain frequency. The week-8 interference-with-life score was lower with agomelatine than with placebo, although the between-group difference in change from baseline was not statistically significant. The responder rate, defined as a reduction of at least 50 points in total IBS-SSS, was higher with agomelatine than with placebo (67.7% vs. 33.3%; p = 0.007). Daily bowel-movement frequency and days with pain, diarrhea, and urgency decreased significantly more with agomelatine (all p < 0.05). Anxiety and depression scores decreased, and IBS-QOL improved, significantly more with agomelatine than with placebo (all p ≤ 0.001). Adverse events were more frequent with agomelatine than placebo (61.3% vs. 23.3%; p = 0.004) and were predominantly mild to moderate. Two participants in the agomelatine group discontinued treatment because of adverse events, compared with none in the placebo group; no serious adverse events were reported. Agomelatine effectively improves gastrointestinal symptoms, psychological distress, and QOL in IBS-D patients and is generally well tolerated, supporting its therapeutic potential.Trial registration: The trial was registered at Iranian Registry of Clinical Trials ( https://irct.behdasht.gov.ir/trial/80432 ) (ID code: IRCT20120215009014N544) on November 30, 2024.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128242","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":"Piribedil attenuates methotrexate-induced nephrotoxicity in rats: associated changes in miR-205/EGLN2, Nrf2, and PERK/ATF4/CHOP-related stress responses.","authors":"Abdel-Gawad S Shalkami, Saad Ali S Aljohani, Ahmed Mohamed Farghly, Nahed A Raslan, Shalam M Hussain, Heba El-Sayed Mostafa, Abrar Khalid Aloufi, Sara E Ibrahim, Noor Alkurdi, Mohammed Hashim Albashir, Ahmed M El-Dessouki","doi":"10.1007/s00210-026-05977-4","DOIUrl":"https://doi.org/10.1007/s00210-026-05977-4","url":null,"abstract":"<p><p>Although microRNAs have been investigated, the renoprotective role of microRNA-205 (miR-205) in methotrexate (MTX)-induced nephrotoxicity remains unclear. Accordingly, this study examined changes in miR-205 and its established target EGLN2 in relation to oxidative and endoplasmic reticulum stress responses during piribedil treatment. Rats were randomly divided into four groups (n = 8/group): a normal control group, an MTX group that received a single intraperitoneal injection of methotrexate (20 mg/kg) on day 7, and two piribedil-treated groups that received piribedil orally at 25 or 50 mg/kg/day for 10 consecutive days, with MTX administered on day 7. At the end of the study, blood and kidney samples were collected for biochemical, histopathological, immunohistochemical, and qRT-PCR analyses. MTX induced significant renal impairment, as indicated by increased SCr, BUN, NGAL, and KIM-1, together with marked histopathological alterations. These changes were accompanied by decreased miR-205 and increased EGLN2 expression, alterations in Nrf2-related antioxidant markers, elevated PC levels, and increased PERK/eIF2α/ATF4/CHOP-related ER-stress markers (p < 0.01). In parallel, MTX increased JNK1 and FOS expression, NF-κB p65 immunoreactivity, pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and apoptosis-related markers including caspase-12, caspase-9, and caspase-3 (p < 0.01). Piribedil attenuated renal functional and structural injury, accompanied by reciprocal changes in miR-205/EGLN2 expression and improvement in the investigated antioxidant, ER-stress-, inflammatory-, and apoptosis-related markers. These findings support further evaluation of piribedil as a potential renoprotective agent and indicate that its protective effect in MTX-induced renal injury is accompanied by alterations in miR-205/EGLN2 expression and related cellular stress-response markers.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112268","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":"Dimethyl fumarate attenuates cadmium-induced neurobehavioural deficits, NF-κB/NLRP3-associated neuroinflammation and synaptic protein alterations in rats.","authors":"Bolaji Samuel Mesole, Alfred Omachonu Okpanachi, Rademene Sunday Oria, Mwitwa Kombe, Sharon Kaundu, Jonathan Chinyama, Tuesday Kafunda, Kebe Edet Obeten, Uthman Ademola Yusuf","doi":"10.1007/s00210-026-05982-7","DOIUrl":"https://doi.org/10.1007/s00210-026-05982-7","url":null,"abstract":"<p><p>Cadmium (Cd) exposure is associated with cognitive dysfunction, neuroinflammation and synaptic impairment. This study evaluated whether dimethyl fumarate (DMF) attenuates CdCl₂-induced neurotoxicity in rats and whether protection is associated with reduced NF-κB/NLRP3-associated inflammatory signalling and preservation of synaptic proteins. Male Wistar rats received control, CdCl₂ (5 mg/kg/day), DMF (25 mg/kg/day) or CdCl₂ + DMF treatment orally for 30 days (n = 8/group). CdCl₂ impaired spatial learning, recognition memory, spontaneous alternation and exploratory activity; increased TNF-α, IL-1β and IL-6; enhanced NF-κB p65 expression/phosphorylation and NLRP3, ASC and cleaved caspase-1 and reduced BDNF, synaptophysin, PSD-95 and NMDAR subunits in the hippocampus and prefrontal cortex. DMF significantly attenuated these behavioural and molecular alterations. These findings indicate that DMF reduces CdCl₂-induced neurobehavioural and molecular toxicity in association with suppression of NF-κB/NLRP3-associated inflammatory signalling and preservation of neurotrophic and synaptic protein profiles.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112063","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":"Correction: Kramersmeyer R, Schirmer B, Seifert R. Pharmacological content in the German tabloid newspaper BILD: Comparison with DIE ZEIT. Naunyn Schmiedebergs Arch Pharmacol. 2026 Sep 24. doi: 10.1007/s00210-026-05892-8. Epub ahead of print. PMID: 42778760.","authors":"Ramona Kramersmeyer, Bastian Schirmer, Roland Seifert","doi":"10.1007/s00210-026-05981-8","DOIUrl":"https://doi.org/10.1007/s00210-026-05981-8","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127436","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}