Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"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}

{"title":"Omega-3 pretreatment attenuates hepatic inflammatory histopathology in LPS-Induced rat endotoxemia: exploratory SIRT1/HO-1 findings.","authors":"Hatice Akpinar, Orhan Akpinar, Halil Asci, Muhammet Yusuf Tepebasi, Burak Yildirim, Osman Aydin, Ozlem Ozmen","doi":"10.1007/s00210-026-05976-5","DOIUrl":"https://doi.org/10.1007/s00210-026-05976-5","url":null,"abstract":"<p><p>Sepsis is a major global contributor to morbidity and mortality, and liver dysfunction intensifies disease severity. Lipopolysaccharide (LPS)-induced liver injury is characterized by inflammation, oxidative stress, and apoptosis, whereas the sirtuin-1 (SIRT1) and nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) pathway provides essential cellular protection. Although omega-3 (OMG3) polyunsaturated fatty acids are recognized for their anti-inflammatory and antioxidant properties, their effects on this pathway remain unclear. This study investigated the hepatoprotective effects of OMG3 pretreatment against LPS-induced hepatic injury in rats, evaluating histopathological injury as the primary endpoint together with hepatic SIRT1, NRF2, and HO-1 expression, inflammatory/apoptotic markers, and redox status as secondary/exploratory outcomes. Thirty-two female Wistar Albino rats were assigned to four groups: control, LPS (5 mg/kg, i.p.), LPS + OMG3, and OMG3 (0.5 g/kg/day, i.p.). Liver tissues were analyzed by histopathology, immunohistochemistry, RT-qPCR, and oxidative stress assays, including total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). LPS produced significant histopathological damage (hemorrhage, inflammation, and necrosis scores; all p ≤ 0.003 vs. control), increased immunoreactivity of Caspase-3, NF-κB, TNF-α, and VEGF (all p ≤ 0.005), decreased hepatic SIRT1 and HO-1 mRNA expression (p = 0.015, p = 0.009), and elevated OSI (p < 0.001). Three-day OMG3 pretreatment significantly reduced the histopathological inflammation score versus LPS (adjusted p = 0.037); reductions in hemorrhage and necrosis scores, Caspase-3/NF-κB/TNF-α/VEGF immunoreactivity, SIRT1/HO-1 mRNA expression, and TAS/OSI were directionally favorable but did not reach significance (adjusted p = 0.050-0.763). NRF2 expression and TOS did not differ among groups. Under this prophylactic regimen, 3-day OMG3 pretreatment significantly attenuated the histopathological inflammatory response to acute LPS-induced hepatic injury. Reductions in apoptotic, inflammatory, and angiogenic immunoreactivity, hepatic SIRT1/HO-1 expression, and redox indices were directionally consistent but statistically unconfirmed in the LPS + OMG3-versus-LPS comparison, and should be interpreted as exploratory. Activation of the SIRT1-NRF2/HO-1 pathway was not established at the protein level, and further dose-ranging and mechanistic studies are needed before extrapolating these findings to a therapeutic context.</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":"149112281","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":"Hepatic drug transporters in pharmacotherapy: mechanisms, therapeutic targeting, and clinical translation.","authors":"Abdul Shadab","doi":"10.1007/s00210-026-05971-w","DOIUrl":"https://doi.org/10.1007/s00210-026-05971-w","url":null,"abstract":"<p><p>Hepatic membrane transporters are key determinants of drug disposition, hepatocellular exposure, pharmacodynamic response, drug-drug interactions (DDIs), and hepatobiliary toxicity. Among these, the organic anion transporting polypeptides OATP1B1 and OATP1B3, sodium taurocholate cotransporting polypeptide (NTCP), and bile salt export pump (BSEP) coordinate hepatic uptake and biliary efflux of endogenous compounds, therapeutic agents, and metabolites. Their role in transporter-mediated pharmacokinetics, exposure-response relationships, therapeutic efficacy, DDIs, and drug-induced liver injury (DILI) is critically reviewed. Specific focus is placed on transporter inhibition, competition, saturation, and disease-associated regulation that can lead to clinically relevant changes in hepatic and systemic drug exposure. Pharmacogenomic variation, including variation in SLCO1B1, SLCO1B3, SLC10A1, and ABCB11, is considered together with inflammation and chronic liver disease as determinants of transporter phenotype and interindividual variability. BSEP is described in more detail as a key hepatobiliary safety determinant including impaired bile-acid export, cholestatic liability, and implications for DILI assessment and drug development. Clinical evidence is differentiated from pre-clinical transporter-targeting concepts. NTCP-directed antiviral therapy is an important example of clinical pharmacological translation, while many transporter-guided delivery systems are still experimental. Therefore, selected prodrug, ligand-directed, and nanocarrier strategies are only discussed where transporter engagement is associated with pharmacokinetic, pharmacodynamic, efficacy, safety, or translational consequences. Finally, transporter-informed PBPK modeling, human-relevant models, and biomarker-guided stratification are discussed to improve DDI prediction, risk assessment, and precision dosing. This pharmacology-focused framework defines when transporter modulation or targeting may be therapeutically beneficial and when it may introduce pharmacokinetic or safety liabilities.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112156","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":"Triptolide as a multi-target anticancer agent: molecular mechanisms and translational potential.","authors":"Md Shadin, Md Shakil Hossain, Sagor Mandal, Prachurjo Kumar Swadesh, Bikram Sana, Md Ripon, Mehedi Hasan Linkon, Md Adam Shafiulla, Muftarin Zaman Aivy, Md Shourov Hossen, Muhammad Torequl Islam, Muhammad Ali Khan, Mohsin Kazi","doi":"10.1007/s00210-026-05963-w","DOIUrl":"https://doi.org/10.1007/s00210-026-05963-w","url":null,"abstract":"<p><p>Triptolide, a bioactive diterpenoid epoxide isolated from Tripterygium wilfordii Hook. F. (Thunder God Vine), is a potent multi-target natural compound with significant anticancer potential. This systematic review with narrative synthesis evaluates preclinical evidence published between 2015 and 2026 on its molecular mechanisms, cancer-specific responses, and translational prospects, introducing a confidence-based framework to grade the strength of reported mechanisms. Across 51 studies, triptolide showed broad-spectrum anticancer activity in breast, lung, colorectal, pancreatic, hepatocellular, ovarian, prostate, glioma, and osteosarcoma models, acting mainly through mitochondrial apoptosis (92% of studies), reactive oxygen species generation, cell-cycle arrest, and modulation of NF-κB, PI3K/Akt/mTOR, STAT3, and Wnt/β-catenin signaling, with chemosensitization to cisplatin, gemcitabine, pemetrexed, and gefitinib reported in 31% of studies. Clinical translation, however, remains constrained by a therapeutic-index paradox: the same multi-target actions driving efficacy also underlie systemic toxicity, compounded by poor aqueous solubility, low bioavailability, and a narrow therapeutic window. The prodrug Minnelide has reached phase I/II trials, but substantial toxicity persists and no phase III data yet exist. Future progress will likely depend on improved delivery and toxicity-mitigation strategies rather than the discovery of additional molecular targets.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112243","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":"Adverse drug reactions to first-line anti-tuberculosis treatments, associated factors, and treatment outcomes: a retrospective study from Southern Morocco.","authors":"Omar Er-Rguibi, Hasnae Dahdah, Habiba Saou","doi":"10.1007/s00210-026-05983-6","DOIUrl":"https://doi.org/10.1007/s00210-026-05983-6","url":null,"abstract":"<p><p>Tuberculosis (TB) treatment is often associated with adverse drug reactions (ADRs) of varying severity, which may negatively affect treatment adherence and outcomes. This study aimed to identify ADRs related to first-line anti-TB drugs, determine associated factors, and evaluate treatment outcomes among TB patients in the Laâyoune-Sakia El Hamra region of Morocco. A retrospective study was conducted in southern Morocco from January 1, 2023 to December 31, 2024. Data were collected from clinical charts of TB patients treated at the Center for Tuberculosis and Respiratory Diseases of Laâyoune (CDTMRL). Adverse drug reactions were evaluated by a specialist clinician throughout treatment, and outcomes were assessed according to World Health Organization guidelines. Among 354 TB patients, 26.55% experienced ADRs, most commonly during the intensive treatment phase. ADRs were significantly associated with gender, age, smoking status, and comorbidities, particularly diabetes and HIV infection. The majority of ADRs were hepatic (13.87%) and gastrointestinal (9.83%). Cutaneous (6.36%), articular (6.07%), and renal (5.78%) ADRs occurred at similar frequencies. Neurological, immunoallergic, cardiovascular, and urogenital ADRs were comparatively less frequent. Most reactions were mild to moderate and managed symptomatically, with few requiring treatment modifications and no ADR-related deaths. Treatment success outcomes were achieved in 81.1% of patients and unsuccessful treatment accounted for 10.73%. Adverse reactions to first-line anti-TB medications are relatively common and highlight the need for close clinical monitoring throughout the treatment period. Strengthening pharmacovigilance and improving patient education may help enhance treatment adherence and reduce complications.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112391","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":"Ursolic acid ameliorates metabolic dysfunction-associated fatty liver disease by regulating the NOX4/ROS/NLRP3 pathway.","authors":"Jian Chen, Yuan Nie, Hu Li, Changlong Wen","doi":"10.1007/s00210-026-05965-8","DOIUrl":"https://doi.org/10.1007/s00210-026-05965-8","url":null,"abstract":"<p><p>Ursolic acid (UA) is a monomeric traditional Chinese medicine with unique anti-inflammatory properties. Metabolic fatty liver (MAFL)/metabolic steatohepatitis (MASH) is an early/progressive stage of metabolic dysfunction-associated fatty liver disease (MAFLD). Whether UA affects the progression of MAFLD and whether it is related to the ROS/TXNIP/NLRP3 pathway have not been reported. Wild-type (WT), NLRP3^-/-, and NOX4^-/- mice and Apocynin (AP)-treated mice were fed a low-fat or high-fat diet for 24 weeks and treated with or without UA for 6 weeks. ELISA and histological analysis were used to assess liver injury and lipid deposition. RT-qPCR, Western blotting and immunofluorescence were conducted to measure the mRNA and protein expression of factors related to inflammation, lipid metabolism, liver fibrosis and NOX4/ROS/NLRP3. UA treatment attenuated HFD-induced lipid deposition, inflammation and fibrosis. This was demonstrated by decreases in weight, liver enzymes, triglycerides, lipid deposition, and the expression of proinflammatory factors (TNF-a, IL-1β, IL-6), lipid metabolism-related factors (FAS, SREBP1, ACC1), and liver fibrosis-related factors (α-SMA, collagen-1, TIMP-1) and an improvement in glucose tolerance and insulin tolerance. The levels of NOX4, ROS, and NLRP3 were significantly inhibited by UA treatment in HFD-fed mice, and the progression of MAFLD was also significantly decreased in NLRP3^-/-, NOX4^-/-, and AP-treated mice without UA treatment. Moreover, the expression of NLRP3 was significantly inhibited in NOX4^-/- and AP-treated mice. UA may attenuate MAFLD-related lipid deposition, liver inflammation and fibrosis in vivo through the NOX4/ROS/NLRP3 pathway. UA treatment may provide a new approach for NASH therapy in humans.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112279","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":"Engineering a chitosan-based nanoemulsion for non-invasive CNS-targeting approach: dual neuroprotection against epileptic and depressive disorders.","authors":"Samar M Mahgoub, A B M Sharif Hossain, Ahmed A Allam, Rehab Mahmoud, Haifa E Alfassam, Fatma I Abo El-Ela","doi":"10.1007/s00210-026-05947-w","DOIUrl":"https://doi.org/10.1007/s00210-026-05947-w","url":null,"abstract":"<p><p>The frequent comorbidity of epilepsy and depression presents a major therapeutic challenge, with current therapies limited by systemic side effects and poor blood-brain barrier penetration. This study aimed to develop a non-invasive, dual-therapy topical nanoemulsion for combined (additive), rather than formally demonstrated synergistic, neuroprotection. A Quality-by-Design optimized chitosan-lipid nanoemulsion co-encapsulating ashwagandha extract and citicoline was engineered. The formulation exhibited favorable characteristics: nanoscale size (~ 145 nm), positive zeta potential (+ 35.9 mV), and sustained in vitro drug release. Its efficacy was evaluated in rat models of acute strychnine-induced seizures and forced swimming test-induced depression following topical application to the shaved head region. The treatment significantly attenuated seizure severity and latency in the acute seizure model. Concurrently, it reversed depressive-like behaviors across multiple tests (Forced Swim Test, FST; Tail Suspension Test, TST; and Sucrose Preference Test, SPT), with efficacy surpassing oral fluoxetine. Histopathological analysis of brain tissue confirmed pronounced neuroprotection in both models. This chitosan-based topical nanoemulsion presents a promising, patient-compliant strategy for dual neuroprotection against interconnected neurological disorders, offering a proof-of-concept for a novel combinatorial therapeutic approach. Although direct pharmacokinetic confirmation of brain drug distribution remains to be established, the observed pharmacodynamic and histopathological outcomes are consistent with CNS engagement following topical application, supporting further investigation of this delivery platform.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112134","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":"Ciprofloxacin beyond antibacterial therapy: pharmacological mechanisms, anticancer activity, and translational limitations.","authors":"Rezvan Tahmasbi, Mohammad Khalaj-Kondori, Arezu Karimpur-Zahmatkesh","doi":"10.1007/s00210-026-05960-z","DOIUrl":"https://doi.org/10.1007/s00210-026-05960-z","url":null,"abstract":"<p><p>Ciprofloxacin is a widely used fluoroquinolone antibiotic whose biological effects extend beyond bacterial DNA gyrase and topoisomerase IV inhibition. Accumulating preclinical evidence suggests that ciprofloxacin can modulate mammalian cellular pathways involved in tumor growth, regulated cell death, inflammation, and tissue homeostasis. This narrative review summarizes PubMed-indexed evidence on the pharmacological effects of ciprofloxacin beyond antibacterial activity, focusing on DNA and topoisomerase-related mechanisms, mitochondrial dysfunction, apoptosis, cell-cycle regulation, oxidative stress, ferroptosis, autophagy, inflammatory signaling, and tissue remodeling. Evidence concerning the parent ciprofloxacin molecule is considered separately from that involving chemical derivatives, conjugates, nanoparticles, and combination regimens. Overall, the available evidence suggests that the effects of ciprofloxacin on cancer cells and host pathways are context-dependent. However, most of the evidence remains preclinical, and the clinical relevance of concentrations used in many studies remains uncertain. Established fluoroquinolone-associated toxicities should also be considered when evaluating its potential for drug repurposing. Ciprofloxacin may therefore warrant further pharmacological investigation, but it should not yet be considered an established anticancer or host-directed therapy.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112329","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 interplay between vitamin D3 and Nrf2 signaling: mechanistic insights and therapeutic potentials.","authors":"Asal Tajgardan, Abolfazl Azami Tameh, Shirin Barati, Marjan Behdarvandy, Zeinab Vahidinia","doi":"10.1007/s00210-026-05968-5","DOIUrl":"https://doi.org/10.1007/s00210-026-05968-5","url":null,"abstract":"<p><p>Oxidative stress plays a central role in the initiation and progression of numerous pathological conditions, including neurodegenerative, cardiovascular, metabolic, hepatic, and inflammatory disorders. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is recognized as a master regulator of cellular antioxidant defense, mediating the transcription of a wide array of antioxidant and cytoprotective genes. Beyond its classical role in calcium and bone homeostasis, vitamin D3 (VitD3) exerts a broad spectrum of non-classical biological effects. Accumulating evidence highlights its anti-inflammatory, anti-oxidative, anti-angiogenic, and anti-cancer properties, while VitD3 deficiency has been implicated in the pathogenesis of various cardiovascular, inflammatory, and malignant diseases. Among these emerging non-calcemic functions, the antioxidant capacity of VitD3 has gained increasing attention. Recent studies suggest that calcitriol, the active form of VitD3, may modulate the Nrf2 signaling pathway and its downstream protective responses. This review synthesizes current evidence on the potential role of VitD3-mediated Nrf2 modulation across diverse disease models. Collectively, targeting the VitD3-Nrf2 axis may represent a promising mechanistic target for future therapeutic investigation.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112226","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}