Immunopharmacology and Immunotoxicology最新文献

{"title":"Sustained clinical quiescence in anti-Scl-70 positive systemic sclerosis during long-term entecavir therapy: a potential role for NLRP3 inflammasome inhibition?","authors":"Angelo Nigro","doi":"10.1080/08923973.2026.2725840","DOIUrl":"10.1080/08923973.2026.2725840","url":null,"abstract":"","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-3"},"PeriodicalIF":3.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840340","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 effects of histamine H4 receptor antagonist on the inflammatory responses in B cells in a mouse model of multiple sclerosis.","authors":"Haneen A Al-Mazroua, Hussain N Alhamami, Ahmed Nadeem, Mushtaq A Ansari, Saleh A Bakheet, Sabry M Attia, Wedad S Sarawi, Hatun A Alomar, Abdulaziz M S Alsaad, Ali A Alshamrani, Sheikh F Ahmad","doi":"10.1080/08923973.2026.2723386","DOIUrl":"10.1080/08923973.2026.2723386","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) driven by autoimmune mechanisms. However, growing evidence indicates that B lymphocytes may contribute to the disease through antigen presentation and the production of proinflammatory mediators. This study aimed to examine the effect of JNJ 10191584 (JNJ), a potent and selective H4R antagonist, on EAE progression and to uncover the underlying mechanisms.</p><p><strong>Methods: </strong>The research explored the potential impact of H4R antagonists on inflammatory responses in B cells within an EAE mouse model of MS. EAE mice received an oral dose of JNJ at 6 mg/kg daily, starting on day 10 and continuing until day 42. Flow cytometry assessed JNJ's effect on the expression of NF-κB p65, IκBα, Notch1, Notch3, IL-2, IL-6, GM-CSF, iNOS, TNF-α, and MCP-1 in CD19⁺ B cells. We used RT-PCR to assess the impact of JNJ on mRNA levels of these inflammatory markers in brain tissue.</p><p><strong>Results: </strong>In EAE mice, JNJ treatment reduced the number of CD19⁺ cells expressing NF-κB p65, IκBα, Notch1, Notch3, IL-2, IL-6, GM-CSF, iNOS, and MCP-1. Additionally, JNJ decreased mRNA expression of inflammatory markers in brain tissue compared with vehicle-treated mice.</p><p><strong>Conclusions: </strong>These results suggest that targeting H4R with antagonists could offer a new therapeutic approach for MS by specifically modulating B-cell-mediated inflammation.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-10"},"PeriodicalIF":3.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808629","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":"Rosuvastatin and engeletin ameliorate acetic acid-induced ulcerative colitis through modulation of TXNIP/NLRP3-related inflammatory signaling pathway.","authors":"Thanaa A El-Masry, Sally E Abu-Risha, Walaa A Negm, Eman Aly Kamal","doi":"10.1080/08923973.2026.2716666","DOIUrl":"10.1080/08923973.2026.2716666","url":null,"abstract":"<p><strong>Introduction: </strong>Mucosal inflammation is the defining feature of ulcerative colitis (UC), which is a chronic inflammatory bowel disease. The goal of this study was to determine the involvement of the TXNIP/NLRP3 inflammatory pathway in UC development and to assess the therapeutic potential of engeletin and rosuvastatin.</p><p><strong>Material and methods: </strong>Acetic acid (AA) was used to initiate UC. The animals were divided into seven groups: normal control, UC control, UC treated with mesalazine (100 mg/kg/day), UC treated with rosuvastatin (20 mg/kg/day), UC treated with engeletin (25 mg/kg/day), UC treated with engeletin (50 mg/kg/day), and UC treated with a combination of rosuvastatin and engeletin (20 mg and 25 mg/kg/day). All treatments lasted 21 days. Body weight, colon weight, colon length, and weight-to-length ratio were all assessed. ELISA was used to detect IL-1β, MPO, gasdermin-D, NF-κB p65, and TXNIP contents. TXNIP expression was quantified by quantitative real-time PCR, and colon samples were examined histopathologically and immunohistochemically.</p><p><strong>Results: </strong>UC caused significant weight loss, increased colon weight, and a shift in the colon weight-to-length ratio. These changes were associated with elevated inflammatory markers and upregulation of the TXNIP/NLRP3 pathway markers. All measured parameters were significantly improved after treatment with engeletin, rosuvastatin, and their combination, with the combination having the most pronounced therapeutic benefits.</p><p><strong>Conclusion: </strong>In conclusion, this study demonstrated that AA-induced UC was associated with increased expression of TXNIP/NLRP3-related inflammatory markers, which may contribute to the disease pathophysiology. The combination of engeletin and rosuvastatin was associated with downregulation of TXNIP/NLRP3-related inflammatory signaling and amelioration of biochemical and histopathological changes associated with UC.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-14"},"PeriodicalIF":3.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808663","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":"Nephroprotective effect of vitamin E and sodium selenite against azithromycin-induced renal toxicity in a rat model: attenuation of oxidative stress, inflammation, and apoptosis.","authors":"Marwan A Ibrahim, Ibrahim M Ibrahim Laila, Ayman M Algohary, Mai M Anwar","doi":"10.1080/08923973.2026.2725032","DOIUrl":"https://doi.org/10.1080/08923973.2026.2725032","url":null,"abstract":"<p><strong>Background: </strong>Azithromycin (AZM), a widely prescribed macrolide antibiotic, has been increasingly associated with nephrotoxicity mediated by oxidative stress, inflammation, and apoptosis. Antioxidants such as vitamin E and sodium selenite may exert protective effects against drug-induced nephrotoxicity.</p><p><strong>Objectives: </strong>This study aimed to investigate the nephrotoxic effects of AZM and the possible ameliorative effects of vitamin E and sodium selenite in a rat model.</p><p><strong>Methods: </strong>Thirty adult male Wistar rats (180-200 g) were randomly allocated into five groups (n = 6): control, vitamin E (100 mg/kg/day), sodium selenite (0.25 mg/kg/day), AZM (30 mg/kg/day), and AZM + vitamin E + sodium selenite. All treatments were administered orally once daily for 14 days. Renal function biomarkers (serum urea and creatinine) and hemoglobin levels were assessed. Kidney tissues were analyzed for oxidative stress markers (MDA, ROS, protein carbonyl, 8-OHdG), inflammatory mediators (MPO, NO, TNF-α), and apoptotic markers (caspase-3, cytochrome-c, p53), together with histopathological examination and apoptotic staining. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test <b>(</b>p < 0.05<b>)</b>.</p><p><strong>Results: </strong>AZM administration significantly elevated renal function markers, oxidative stress indices, inflammatory cytokines, and apoptotic signaling, accompanied by marked histopathological injury and increased caspase-3 expression. Conversely, co-administration of vitamin E and sodium selenite markedly attenuated detected biochemical alterations, improved renal functions, and restored renal architecture.</p><p><strong>Conclusion: </strong>Subacute AZM exposure induces significant functional and histopathological renal alterations. Co-administration of vitamin E and sodium selenite confers marked nephroprotection mediated through antioxidant and anti-apoptotic actions. These findings suggest combined therapeutic potential in attenuating AZM-induced renal toxicity.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-20"},"PeriodicalIF":3.1,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818311","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":"Paulownin: a promising agent In the fight against the invasion and immune escape in triple-negative breast cancer.","authors":"Shaojie Qin, MingLiang Ning, Pei Wang, Qingyuan Liu","doi":"10.1080/08923973.2026.2716752","DOIUrl":"https://doi.org/10.1080/08923973.2026.2716752","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most prevalent malignancy among females. Paulownin has anti-tumor properties and immune-modulating activities in various cancers; however, its effects on breast cancer remain inadequately understood.</p><p><strong>Aims: </strong>This study aimed to elucidate the impact of Paulownin on breast cancer and the regulatory mechanisms.</p><p><strong>Methods: </strong>The cell viability and invasiveness were explored by CCK-8 and Transwell in MDA-MB-231 and BT549 cells. A co-culture system was established using activated CD8⁺ T cells and MDA-MB-231 or BT549 cells for 24 h. Cell apoptosis was assessed using flow cytometry. The IFN-γ level was analyzed <i>via</i> ELISA. <i>In vivo</i>, the roles of Paulownin were explored in HuPBMC-(M-NSG) mice and detected by immunohistochemistry and western blot.</p><p><strong>Results: </strong>Paulownin decreased the viability of MDA-MB-231 (IC50 = 32.54 μM) and BT549 (IC50 = 38.15 μM) cells. Paulownin reduced the levels of Ki-67 and Vimentin, increased E-cadherin expression, and impaired the invasive capabilities. Paulownin also inhibited PD-L1 expression in MDA-MB-231 and BT549 cells after co-cultured with CD8⁺ T cells. Paulownin prevented the apoptosis and elevated IFN-γ levels in CD8⁺ T cells. Additionally, Paulownin suppressed the activity of the AKT/NF-κB signaling pathway. The use of the AKT activator SC79 counteracted the effects of Paulownin on breast cancer cell growth, invasion and immune escape. <i>In vivo</i>, Paulownin inhibited tumor growth, decreased Ki-67 and Vimentin levels, increased E-cadherin, CD8 and IFN-γ levels and suppressed the AKT/NF-κB pathway activation.</p><p><strong>Conclusion: </strong>Paulownin restricted breast cancer cell proliferation, invasion, and immune escape. The mechanism may involve the inactivation of the AKT/NF-κB signaling.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-9"},"PeriodicalIF":3.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808661","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":"https://doi.org/10.1080/08923973.2026.2722387","url":null,"abstract":"<p><strong>Background: </strong>Isoflurane exhibits protective roles on 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 factors level and oxidative stress were aggravated. The results showed an opposite trend with isoflurane pre-treatment. However, after HOXA11-AS overexpression, cell damage was further aggravated. HOXA11-AS is a molecular sponge for miR-130b-3p. It was revealed that the cell viability was improved, the inflammatory response and oxidative stress were weakened after transfection with 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 in H/R model.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-12"},"PeriodicalIF":3.1,"publicationDate":"2026-08-24","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":"Wogoniol, a novel radiolytic derivative of wogonin, programs dendritic cells for immune tolerance: suppression of T helper 1/17 and promotion of regulatory T cells.","authors":"Ha-Yeon Song, Gyeong Han Jeong, Hyoung-Woo Bai, Eui-Baek Byun","doi":"10.1080/08923973.2026.2713463","DOIUrl":"https://doi.org/10.1080/08923973.2026.2713463","url":null,"abstract":"<p><strong>Background: </strong>Tolerogenic dendritic cells (tolDCs) play a pivotal role in maintaining immune homeostasis by driving regulatory T cell (Treg) differentiation. Modulating DC phenotypes to restore immune tolerance is a primary therapeutic goal for controlling inflammatory responses.</p><p><strong>Objectives: </strong>Here, we investigate the immunoregulatory mechanisms of wogoniol, a novel non-planar radiolytic derivative of the phytochemical wogonin featuring a C2-hydroxymethyl group, on DC-T cell crosstalk.</p><p><strong>Methods: </strong>The immunomodulatory effects of wogoniol were evaluated using lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) and <i>in vitro</i> DC-T cell co-culture systems. Intracellular signaling mechanisms driving the DC phenotype were analyzed and validated using specific pharmacological inhibitors.</p><p><strong>Results: </strong>In LPS-stimulated bone marrow-derived dendritic cells (BMDCs), the parent wogonin acted as a nonspecific inhibitor, suppressing both pro- (TNF-α and IL-12p70) and anti-inflammatory (IL-10) cytokines. In contrast, wogoniol induced a stable tolDC phenotype, suppressing TNF-α and IL-12p70 while significantly upregulating the anti-inflammatory cytokine IL-10 and immunosuppressive molecule PD-L1. Mechanistically, wogoniol suppressed JNK phosphorylation while activating p38 and STAT3. Pharmacological inhibition confirmed that these pathways are essential for the observed tolerogenic phenotype. In subsequent DC-T cell co-cultures, wogoniol-treated DCs potently suppressed Th1 (T-bet/IFN-γ) and Th17 (RORγt/IL-17A) differentiation while strongly promoting the induction of CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs) to a level comparable to dexamethasone.</p><p><strong>Conclusions: </strong>Wogoniol exhibits a potent immune skewing mechanism absent in its parent compound, programming DCs to suppress pathogenic Th1/Th17 responses while actively inducing Foxp3⁺ Tregs. These findings establish wogoniol as a promising new pharmacological candidate for inducing immune tolerance.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-17"},"PeriodicalIF":3.1,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758718","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":"Ivabradine alleviates the cisplatin-induced cardiotoxicity in rats through regulating the crosstalk between MLCP/PKG, MEK/ERK pathways and miRNA-34a levels.","authors":"Nayef A Aldabaan, Basel A Abdel-Wahab, Ehab A M El-Shoura, Saad Misfer Alqahtani, Marwa B Bakir, Hebatallah M Saad, Zainab Mohammed Mahmoud Omar, Dalia Zaafar","doi":"10.1080/08923973.2026.2713465","DOIUrl":"10.1080/08923973.2026.2713465","url":null,"abstract":"<p><strong>Background: </strong>Ivabradine (IVA), a broad-spectrum hyperpolarization-activated cyclic nucleotide-gated (HCN) channel inhibitor, improves cardiac function in cardiovascular diseases and may protect against drug-induced cardiotoxicity. This study investigated the cardioprotective effects of IVA against cisplatin (Cis)-induced cardiac injury and explored the underlying molecular mechanisms.</p><p><strong>Methods: </strong>Rats received IVA (5 mg/kg, orally) for 28 consecutive days and Cis (7.5 mg/kg, intraperitoneally) on day 5. Cardiac oxidative stress biomarkers, inflammatory cytokines, histopathological alterations, and molecular signaling pathways were evaluated using biochemical assays, H&E staining, western blotting, PCR, and immunohistopathology.</p><p><strong>Results: </strong>IVA markedly improved cardiac histoarchitecture and attenuated Cis-induced pathological alterations. It exerted antioxidant and anti-inflammatory effects by reducing malondialdehyde (MDA), NADPH oxidase, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 levels, while increasing superoxide dismutase (SOD), IL-10, and endothelial nitric oxide synthase (eNOS). IVA downregulated cAMP response element-binding protein (CREB), extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase kinase (MEK), protein kinase C-epsilon (PKCε), and microRNA-34a (miRNA-34a), while upregulating protein kinase G (PKG), myosin light chain phosphatase (MLCP), and rapidly accelerated fibrosarcoma-1 (Raf-1). Furthermore, IVA enhanced cardiac cell survival, as evidenced by increased B-cell lymphoma 2 (Bcl-2) expression and reduced caspase-3 immunostaining.</p><p><strong>Conclusion: </strong>IVA significantly attenuates Cis-induced cardiotoxicity through antioxidant, anti-inflammatory, anti-apoptotic, and miRNA-34a-mediated mechanisms involving multiple cardioprotective signaling pathways.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-13"},"PeriodicalIF":3.1,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663822","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":"A closer insight into the molecular effect of canagliflozin on gentamicin-induced nephrotoxicity in rats: attention to SIRT1/Nrf2/HO-1, p38 MAPK/NF-κB signaling pathways, and expression of miR-21 and miR-155.","authors":"Manar A Gamaan, Heba S Zaky, Hebatalla I Ahmed","doi":"10.1080/08923973.2026.2713468","DOIUrl":"10.1080/08923973.2026.2713468","url":null,"abstract":"<p><p><b>Objective:</b> Nephrotoxicity is considered the most detrimental effect of gentamicin (GM). In this study, we investigated the potential effects for canagliflozin (CANA) to protect against GM-induced nephrotoxicity, besides the multiple molecular pathways underlying these effects.<b>Methods:</b> Four groups with six rats in each were used: control; GM (100 mg/kg, intraperitoneal injection) for 7 days; CANA + GM group: Rats were given CANA (10 mg/kg, by oral gavage) for 14 days, and GM (100 mg/kg, by IP) was co-administered with CANA in the last 7 days; and CANA group: Rats were given CANA (10 mg/Kg, by oral gavage) for 14 days.<b>Results</b>: Relative to GM-challenged rats, CANA ameliorated GM-induced changes in the state of oxidative stress. Also, CANA alleviated the GM-evoked reduction in the renal expression of SIRT1 and Nrf2. Furthermore, CANA decreased the renal expression of NF-ҡB and reduced p38-MAPK levels in kidneys of GM-treated animals. Simultaneously, GM-induced changes in the renal expression of miR-21 and miR-155 have been successfully amended by CANA.<b>Conclusion:</b> Altogether, current outcomes imply that modification of the SIRT1/Nrf2/HO-1, the p38-MAPK/NF-ҡB pathways, and microRNAs (miRNAs) play an important role adressing CANA's 'protective properties against GM nephrotoxicity.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-12"},"PeriodicalIF":3.1,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663762","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":"https://doi.org/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":"1-16"},"PeriodicalIF":3.1,"publicationDate":"2026-08-03","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}