Immunopharmacology and Immunotoxicology最新文献

{"title":"Inhibition of xanthine oxidase protects against heatstroke-related acute kidney injury.","authors":"Wenting Chen, Yongwei Song, Yue Jia, Fei Xiao, Mingyang Zhang, Chun Lan, Xuesen Yang, Ling Wang, Huanzi Dai","doi":"10.1080/08923973.2026.2746674","DOIUrl":"10.1080/08923973.2026.2746674","url":null,"abstract":"<p><strong>Background: </strong>Heatstroke-induced acute kidney injury (HS-AKI) is a critical type of visceral injury. This study aimed to explore whether xanthine oxidase (XOD) promotes the progression of HS-AKI and whether febuxostat (Feb) attenuates HS-AKI through the inhibition of oxidative stress.</p><p><strong>Materials and methods: </strong>Both <i>in vitro</i> (HK-2 cells) and <i>in vivo</i> (a mouse model) approaches were used to evaluate the role of XOD in HS-AKI. <i>In vitro</i>, genetic gain-/loss-of-function (mediated by an <i>XDH</i> overexpression plasmid/siRNA) and pharmacologic intervention (febuxostat) were performed in HK-2 cells exposed to hyperthermia. <i>In vivo</i>, C57BL/6 mice were pretreated with febuxostat (or saline) before heat exposure, and the Control, Feb, HS, and Feb + HS groups were established. Quantitative proteomics was used to screen for proteins that were differentially expressed under thermal stress. Renal function, histopathology, oxidative stress (ROS, MDA, and SOD levels), expression levels of the cytoprotective protein HO-1, inflammatory cytokine (TNF-α and IL-1β), and apoptosis were thoroughly analyzed.</p><p><strong>Results: </strong>Proteomic analysis revealed upregulated expression of XOD in the HS group compared with the control group. The activity and expression of the XOD enzyme were considerably higher in a high heat environment. XOD overexpression significantly increased HS-induced oxidative stress, the inflammatory response, and apoptosis in renal tubular epithelial cells. The inhibition of XOD with febuxostat markedly reduced oxidative stress, thereby preventing inflammation and apoptosis and alleviating HS-AKI.</p><p><strong>Conclusion: </strong>XOD-driven oxidative stress is a key pathogenic mechanism in HS-AKI. Febuxostat, a XOD inhibitor, showed protective efficacy in an animal model, highlighting this pathway as a potential therapeutic target.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-15"},"PeriodicalIF":3.1,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136358","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 lung-gut axis and airway inflammation in COPD.","authors":"Hua Huang, Shuai Huang, Xuhao He, Mingxing Wang","doi":"10.1080/08923973.2026.2746677","DOIUrl":"https://doi.org/10.1080/08923973.2026.2746677","url":null,"abstract":"<p><strong>Objective: </strong>Chronic obstructive pulmonary disease (COPD) is a common lung disease characterized by multiple persistent respiratory symptoms and decreased lung function. Despite extensive research exploring the complex pathogenic mechanisms and signaling pathways underlying COPD, there are currently no effective disease-modifying drugs capable of halting or reversing progressive lung damage, standard interventions including bronchodilators, long-term oxygen therapy and pulmonary rehabilitation merely alleviate clinical symptoms while failing to arrest disease progression, accompanied by unavoidable adverse effects. Against this backdrop, microbiota-targeted interventions emerge as a promising alternative therapeutic strategy. This drives the urgent need to dissect unrecognized pathogenic pathways and develop novel prevention and treatment strategies.</p><p><strong>Methods: </strong>This narrative review summarizes recent data on gut microbiota dysregulation and gut-lung crosstalk in COPD, highlighting immune-mediated gut-lung crosstalk mechanisms, including the shared mucosal immune system and metabolite-induced modulation of pulmonary structure and function.</p><p><strong>Results: </strong>In addition to immune inflammation and hypoxia, COPD patients usually have gastrointestinal complications and gut microbiota (GM) dysregulation. Role of GM in regulating the functional development of the host immune system, and the \"gut-lung axis\" established by GM and the lung also plays a crucial role in regulating lung inflammation and airway function. This may be attributed to the shared mucosal immune system between the gut and lungs, as well as the ability of metabolites to influence lung structure and function. However, the specific pathway of this gut-lung communication in COPD is still unclear.</p><p><strong>Conclusions: </strong>This article reviews the changes of GM related to COPD, and focuses on the mechanism of GM and its metabolites in the occurrence and development of COPD from the immune pathway, so as to find new intervention targets, and highlight the emerging potential of GM interventions (diet, probiotics and prebiotics) for future clinical research and treatment of COPD.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-11"},"PeriodicalIF":3.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181575","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":"Resveratrol reduces inflammatory responses in peripheral blood mononuclear cells from patients with severe asthma.","authors":"Wanessa Maria Dos Santos, Dayana Procópia Macies, Lara Cristina Dos Santos Teodoro, Mirella Castro Queiroz, Jefferson Correia Manso, Beatriz Sodré Matos, Anna Luiza Dos Anjos Oliveiras, Isabella de Oliveira Ferrato de Sousa, Maria Helena de Castro Silva, Daniel Hugo Winter, Leandro de Resende Yamamoto, Alexandre Paula Rogerio","doi":"10.1080/08923973.2026.2747215","DOIUrl":"https://doi.org/10.1080/08923973.2026.2747215","url":null,"abstract":"<p><strong>Background: </strong>Severe asthma is a chronic inflammatory airway disease frequently associated with neutrophilic inflammation, corticosteroid resistance, and persistent activation of pro-inflammatory signaling pathways, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs).</p><p><strong>Objective: </strong>This study aimed to investigate the effects of resveratrol on inflammatory responses in peripheral blood mononuclear cells (PBMCs) obtained from healthy subjects and patients with severe asthma.</p><p><strong>Materials and methods: </strong>PBMCs were stimulated with lipopolysaccharide (LPS; 1 µg/mL) for 24 h in the presence or absence of resveratrol (10^-4-10^-8 M). Cell viability was assessed using the MTT assay, cytokine levels (IL-6, IL-8, and IL-10) were measured by ELISA, and intracellular signaling pathways (NF-κB, ERK1/2, and p38 MAPK) were evaluated by flow cytometry.</p><p><strong>Results: </strong>Resveratrol did not affect cell viability and significantly reduced IL-6 and IL-8 production in a dose-dependent manner in LPS-stimulated PBMCs, without altering IL-10 levels. Additionally, resveratrol attenuated the phosphorylation of NF-κB, ERK1/2, and p38 MAPK in both monocytes and lymphocytes from healthy individuals and patients with severe asthma.</p><p><strong>Discussion and conclusion: </strong>Resveratrol exerts significant anti-inflammatory effects in human PBMCs by modulating cytokine production and key intracellular signaling pathways associated with severe asthma, suggesting its potential as a complementary therapeutic strategy.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-7"},"PeriodicalIF":3.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165442","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":"Vildagliptin attenuates thioacetamide-induced hepatic fibrosis in rats: associations with AMPK/SIRT1/Nrf2 and STAT3/TGF-β1 signaling.","authors":"Mohannad A Almikhlafi, May A Alsayb, Sara A Almadani, Tahani Saeedi, Mohammed H Alsubhi, Alyaa Farouk Hessin, Marwa Mahmoud Fawzy Atta, Reda Ms Korany, Hany M Fayed, Sally A El Awdan, Hossein M Elbadawy","doi":"10.1080/08923973.2026.2741565","DOIUrl":"https://doi.org/10.1080/08923973.2026.2741565","url":null,"abstract":"<p><strong>Objective: </strong>Liver fibrosis is a progressive consequence of chronic injury with limited treatment options. Vildagliptin (Vilda), a dipeptidyl peptidase-4 inhibitor, possesses antioxidant and anti-inflammatory properties, but its effects on thioacetamide (TAA)-induced liver fibrosis are not fully characterized. This study evaluated Vilda in TAA-treated male rats by assessing hepatic function, oxidative stress, and signaling markers.</p><p><strong>Methods: </strong>Rats received TAA (100 mg/kg, i.p., twice weekly for 6 weeks) alone or with Vilda (10 or 20 mg/kg, p.o., daily during weeks 3-6). Serum biochemistry, hepatic antioxidants, and specific protein concentrations (AMPK, p-AMPK, SIRT1, Nrf2, STAT3, p-STAT3, TGF-β1, and AFP) were measured. Liver sections were assessed <i>via</i> H&E, qualitative Masson's trichrome, and immunohistochemistry for p-AKT and SIRT1.</p><p><strong>Results: </strong>TAA impaired liver function, altered lipid profiles, increased oxidative stress, and induced histopathological injury with collagen deposition. These changes coincided with altered hepatic AMPK/SIRT1/Nrf2 and STAT3/TGF-β1-associated markers, alongside PGC-1α and KEAP1 mRNA expression. Vilda treatment was associated with dose-dependent improvements in biochemical, oxidative-stress, and histopathological findings, alongside shifts in inflammation- and fibrosis-associated markers. Vilda was also associated with increased SIRT1 and reduced p-AKT immunoreactivity.</p><p><strong>Conclusion: </strong>Vilda treatment was associated with attenuation of TAA-induced hepatic injury and fibrotic changes in parallel with modulation of AMPK/SIRT1/Nrf2 and STAT3/TGF-β1-related markers. Because quantitative collagen morphometry and pathway-intervention experiments were not performed, these findings represent associations rather than confirmed causal mechanisms. Further studies are required to define the precise molecular interactions and translational potential of Vilda as an antifibrotic agent.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-17"},"PeriodicalIF":3.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164282","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":"Application of antibiotic-loaded bone cement in unicompartmental knee arthroplasty: inhibiting IL-6 levels and reducing postoperative infection rate.","authors":"Dexiang Zhang, Yang Shen, Shaobing Zhang, Xiaolong Xiong","doi":"10.1080/08923973.2026.2725838","DOIUrl":"https://doi.org/10.1080/08923973.2026.2725838","url":null,"abstract":"<p><strong>Objective: </strong>We aim to clarify the inhibitory effect of antibiotic-loaded bone cement (ALBC) on inflammatory factors, and its preventive effect on postoperative infections in unicompartmental knee arthroplasty (UKA).</p><p><strong>Methods: </strong>This prospective randomized controlled trial enrolled 104 osteoarthritis patients undergoing UKA, randomly assigned to the non-ALBC group (<i>n</i> = 52, bone cement without antibiotics) and ALBC group (ALBC with 1.0 g vancomycin hydrochloride, <i>n</i> = 52). Primary outcomes were postoperative inflammatory markers (CRP, ESR, TNF-α, IL-6); secondary outcomes included infection rate and HSS score. Independent-samples t-tests were used for continuous variables, χ² test for categorical variables (infection rate, efficacy), and repeated measures analysis of variance for intra-group longitudinal comparisons.</p><p><strong>Results: </strong>The ALBC group demonstrated lower inflammatory markers at postoperative day 7 and at 3 months [CRP (3.52 ± 0.81 vs 6.92 ± 1.17, Cohen's <i>d</i> = 3.379), ESR (16.29 ± 2.31 vs 20.19 ± 4.05, Cohen's <i>d</i> = 1.183), TNF-α (29.71 ± 4.03 vs 36.25 ± 5.17, Cohen's <i>d</i> = 1.411), and IL-6 (17.05 ± 3.72 vs 22.05 ± 4.38, Cohen's <i>d</i> = 1.230)] (all <i>p</i> < 0.001), and also showed superior clinical outcomes, with lower postoperative infection rate (<i>p</i> = 0.016), higher HSS score (<i>p</i> < 0.001), and better overall clinical efficacy (<i>p</i> = 0.010) than the non-ALBC group.</p><p><strong>Conclusion: </strong>The application of ALBC in UKA was associated with reduced postoperative inflammatory markers such as IL-6 and a lower incidence of postoperative infection. These findings suggest that ALBC may play a beneficial role in postoperative recovery and joint function rehabilitation.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-8"},"PeriodicalIF":3.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165643","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":"Isoflurane regulates the level of HOXA11-AS and affects oxidative stress and inflammation in liver ischemia-reperfusion injury.","authors":"Xiangyang Lin, Xipeng Shen, Haitao Lou, Gang Ou, Kai Zhang","doi":"10.1080/08923973.2026.2722387","DOIUrl":"10.1080/08923973.2026.2722387","url":null,"abstract":"<p><strong>Background: </strong>Isoflurane exhibits protective roles in ischemia-reperfusion injury (IRI), but whether isoflurane can alleviate the inflammation and oxidative stress of LIRI remains unknown.</p><p><strong>Aim: </strong>To explore the effects of isoflurane treatment and HOXA11 antisense long noncoding RNA (HOXA11-AS) expression on LIRI.</p><p><strong>Methods: </strong>AML12 cells were used to construct a hypoxia-reoxygenation (H/R) model. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to test the HOXA11-AS level, microRNA-130b-3p, and phosphatase and tensin homolog (PTEN). Cell viability was detected using the cell counting kit-8 (CCK-8) kit. The content of intracellular inflammatory factors was detected using the enzyme‑linked immunosorbent assay (ELISA) kit. The positive rate of reactive oxygen species (ROS) was detected using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), and the contents of malondialdehyde (MDA) and superoxide dismutase (SOD) enzyme activities were detected using specialized kits. The dual luciferase reporter gene assay was used to verify the targeting relationship.</p><p><strong>Results: </strong>In the H/R model, the levels of HOXA11-AS and PTEN were increased, miR-130b-3p was decreased, cell viability was reduced, inflammatory factor levels were increased and oxidative stress level was aggravated. The results showed an opposite trend with isoflurane pretreatment. However, after HOXA11-AS overexpression, cell damage was further aggravated. HOXA11-AS was a molecular sponge for miR-130b-3p. It was revealed that cell viability was improved, and the inflammatory response and oxidative stress were weakened after transfection with a miR-130b-3p mimic.</p><p><strong>Conclusion: </strong>Isoflurane pretreatment reduced the level of HOXA11-AS, increased the level of miR-130b-3p, enhanced cell viability, and decreased cellular inflammatory factors level and oxidative stress level in the H/R model.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-8"},"PeriodicalIF":3.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808640","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 diverse immunoregulatory role of iodine in thyropathy.","authors":"Chao-Wen Cheng, Wen-Fang Fang, Yea-Mey Yang, Jiunn-Diann Lin","doi":"10.1080/08923973.2026.2702337","DOIUrl":"10.1080/08923973.2026.2702337","url":null,"abstract":"<p><strong>Background: </strong>Iodine is an environmental factor that contributes to the development of autoimmune thyroid diseases (AITDs).</p><p><strong>Objective: </strong>In this study, we evaluated the influence of excessive iodine in initiating and modulating AITD in different mouse models.</p><p><strong>Methods: </strong>We administered exogenous iodide in drinking water (0.15% sodium iodide) to naïve C57BL/6J(B6) mice, human thyroglobulin (hTg)-immunized B6 mice, and a spontaneous autoimmune thyroiditis (NOD.H-2h4) model. We then measured plasma thyroxine (T4) and anti-thyroglobulin antibody (ATA) and gathered microarray data from the Gene Expression Omnibus (GSE16957-GSM424738) for a gene set enrichment analysis (GSEA), ensuring the robustness and validity of our findings.</p><p><strong>Results: </strong>In the hTg-induced thyroiditis model, iodide administration reduced plasma T4 and ATA levels and suppressed hTg-specific splenocytes. In contrast, despite no significant changes in T4 levels, prominent thyroid inflammation and increased CD3⁺ and F4/80⁺ cell infiltration were detected in the iodide administration alone group. On the other hand, after iodide treatment, plasma T4 was reduced but without a significant anti-thyroid extract antibody titer or pathological changes in the NOD.H-2h4 mice. The GSEA showed that human thyrocyte culture incubated with iodide treatment provoked immunologic and inflammatory pathways, including tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, interferon (IFN)-γ, inflammatory responses. Additionally, cell damage (hypoxia-related), immune cell-attracting, and migration-related signatures were also excited.</p><p><strong>Conclusions: </strong>We demonstrated the influence of iodine in initiating thyroid inflammation in naïve mice and human thyrocytes, and modulating the thyroid function in hTg-immunized thyroiditis and NOD.H-2h4 models. Further studies to dissect the actual mechanism are still required.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"749-759"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420934","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":"Matrine pre-intervention protects against inflammatory responses and mucosal injury in rats with gastric ulcer by inhibiting mitochondrial ferroptosis through the PKC/NOX4 pathway.","authors":"Zhu-Sheng Guo, Jin-Yu Zhang, Fei Lv, Jun-Ting Lv, Yin-Sheng Cai, Jian-Bo Feng, Pei-Yu Yan, Jie-Ruo Gu","doi":"10.1080/08923973.2026.2679470","DOIUrl":"10.1080/08923973.2026.2679470","url":null,"abstract":"<p><strong>Objective: </strong>This study sought to investigate whether matrine (MAT) attenuates mitochondrial ferroptosis <i>via</i> the protein kinase C (PKC)/NADPH oxidase 4 (NOX4) pathway and to elucidate its role in inflammation and mucosal injury in the context of gastric ulcer (GU).</p><p><strong>Methods: </strong>An ethanol/hydrochloric acid (EtOH/HCl)-induced GU rat model was established and pretreated with MAT, ferroptosis inducer Erastin, and PKC activator PMA, respectively. <i>In vitro</i>, EtOH-stimulated gastric mucosal epithelial cells (GES-1 and RGM-1) were pre-intervened with MAT in combination with Erastin or PKC modulators. Gastric injury, inflammatory cytokines, ferroptosis-related markers, levels of phosphorylated-protein kinase C (p-PKC), NOX4, and glutathione peroxidase 4 (GPX4) proteins, as well as mitochondrial function, were assessed using H&E staining, ELISA, biochemical assays, western blot, and functional analyses.</p><p><strong>Results: </strong>EtOH/HCl-exposed GU rats showed increased ulcer index, reduced ulcer inhibition rate, along with elevated PKC phosphorylation, and interleukin-6, tumor necrosis factor-α, NOX4, malondialdehyde (MDA) and Fe²⁺ levels in gastric tissues, and decreased superoxide dismutase (SOD) activity, and GPX4 protein and glutathione levels. EtOH intervention resulted in consistent detrimental changes in GES-1/RGM-1 cells. Importantly, MAT pre-intervention markedly reversed these changes in both rat and cell models. Inhibition or silencing of PKC ameliorated mitochondrial dysfunction and ferroptosis <i>in vitro</i>. Moreover, Erastin or PMA administration/PKC overexpression averted the impacts of MAT pre-intervention on GU-associated rat inflammatory responses and GMI, or GES-1/RGM-1 cell mitochondrial dysfunction and ferroptosis.</p><p><strong>Conclusions: </strong>MAT pre-intervention suppressed mitochondrial ferroptosis by inhibiting the PKC/NOX4 pathway, thereby protecting against GMI and inflammatory responses in the GU rat model.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"786-802"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148411658","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":"Preclinical evaluation of 3,4-dimethoxybenzoic acid alone and in combination for adjuvant-induced arthritis in Wistar rats.","authors":"Ammara Saleem, Afnan Afnan, Muhammad Irfan, Aisha Mobashar, Muhammad Furqan Akhtar","doi":"10.1080/08923973.2026.2704103","DOIUrl":"10.1080/08923973.2026.2704103","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis is a systemic autoimmune disorders of joints. Its available therapies having serious adverse effects, high cost and poor patient compliance.</p><p><strong>Objective: </strong>The present study aimed to evaluate the anti-inflammatory and anti-arthritic potential of 3, 4-dimethoxybenzoic acid or Veratric acid (VA) by <i>in-vitro</i> and <i>in-vivo</i> assays. Additionally, acute toxicity of VA was performed.</p><p><strong>Methodology: </strong>The anti-inflammatory activity was assessed by Xylene-induced ear edema, and Carrageenan-induced paw edema models in Wistar rats. The VA was given at doses of 20, 40, and 80 mg/kg, with Piroxicam (10mg/kg) as standard drug. For anti-arthritic action, 0.1 ml of Complete Freund's adjuvant was intradermally inoculated in left posterior paw on first day while treatment with VA at 20, 40, 80, and VA 80 mg/kg + methotrexate and methotrexate (1 mg/kg) as standard drug were given orally on the 8th day for 21 days.</p><p><strong>Results: </strong>Treatment with VA exhibited a substantial reinstatement of body weight, paw edema, arthritic scores, and oxidative stress in difference to disease control. All treatment groups exhibited notable down-regulation (<i>p</i> < .0001) of IL-6, TNF-α, IL-β, COX-2, and NF-κB and up-regulation of IL-10, 1-κβ, IL-4 in contrast to disease control. The combination group had exhibited noticeable anti-arthritic potential in comparison to individual treatment groups. In acute toxicity study, LD₅₀ of VA was greater than 2000 mg/kg.</p><p><strong>Conclusion: </strong>It can be inferenced from data that VA can be safely used to treat arthritis especially in combination with MTX but it should be further evaluated in combination for long term use.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"767-778"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548867","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":"Flavonoids in rosacea therapy: multi-target mechanisms from preclinical models to clinical translation.","authors":"Meng Chen, Xinru Hu, Bowen Tan, Xi Duan","doi":"10.1080/08923973.2026.2686946","DOIUrl":"10.1080/08923973.2026.2686946","url":null,"abstract":"<p><strong>Background: </strong>Recent years, natural plant components, especially flavonoids, known for their anti-inflammatory, antioxidant, and immunomodulatory properties, show potential in the treatment of rosacea.</p><p><strong>Objective: </strong>This review aims to synthesize and critically evaluate the advancements in the therapeutic application of flavonoid compounds for rosacea, encompassing both clinical studies and experimental outcomes from <i>in vitro</i> and <i>in vivo</i> models, thereby providing a reference for future research directions and treatment strategies.</p><p><strong>Methods: </strong>A systematic literature search was conducted in Web of Science, PubMed, ScienceDirect, Wiley, and Embase up to 26 September 2024, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a comprehensive set of rosacea- and flavonoid-related keywords.</p><p><strong>Results: </strong><i>In vitro</i> studies indicate that flavonoids modulate the Sirtuin 3 (SIRT3)-Superoxide Dismutase 2 (SOD2)-Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) axis and suppress inflammatory mediators such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-17 (IL-17). They also regulate Vascular Endothelial Growth Factor (VEGF), Transient Receptor Potential Vanilloid 1 (TRPV1), Kallikrein-related Peptidase 5 (KLK5), and Protease-Activated Receptor 2 (PAR2), contributing to neurogenic inflammation control and skin barrier repair. <i>In vivo</i> models show reduced inflammatory infiltration and angiogenesis. Early clinical studies suggest good safety profiles and potential synergy with standard therapies, though larger Randomized Controlled Trials (RCTs) are needed.</p><p><strong>Conclusions: </strong>Flavonoids exert multi-target effects in rosacea <i>via</i> anti-inflammatory and vascular-modulating mechanisms. Future research should prioritize advanced neuroimmune models, enhanced delivery systems, and patient stratification approaches to optimize clinical application.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"803-818"},"PeriodicalIF":3.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663729","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}