International immunopharmacology最新文献

{"title":"Corrigendum to \"Alteration of immunomodulatory properties of locally applied gingival-derived mesenchymal stem cells by the oral inflammatory environment via Caspase-3/8 in periodontitis\" [Int. Immunopharmacol. 161 (2025) 114978].","authors":"Zhong Li, Ze Zhao, Bin Gu, Fei Duan, Qi Chen, Pengli Li, Yanyi Wang, Tong Zhang, Ning Wen","doi":"10.1016/j.intimp.2025.115292","DOIUrl":"10.1016/j.intimp.2025.115292","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"115292"},"PeriodicalIF":4.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MCC950 attenuates thyroidectomy-induced retching-like behavior by inhibiting NLRP3-mediated IL-1β release","authors":"Lan-Xin Li ,&nbsp;Wen-Guang Li ,&nbsp;Xiao-Yi Ma ,&nbsp;Xu-Peng Wang ,&nbsp;Si-Zheng Liu ,&nbsp;Zhi-Sheng Ji ,&nbsp;Yue Gao ,&nbsp;Li-Min Zhang","doi":"10.1016/j.intimp.2025.115541","DOIUrl":"10.1016/j.intimp.2025.115541","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative nausea and vomiting (PONV) are common complication following surgical procedures, which can significantly impair the quality of patient care, delay discharge, and hinder the resumption of daily activities. In clinical practice, the incidence of PONV after thyroid surgery is approximately 30 %, with a higher prevalence among female patients. Although existing studies have identified various risk factors, treatment methods, and preventive strategies for PONV, research progress in this field has been relatively slow in recent years. Given that rodents lack a functional emetic reflex, precluding direct observation of vomiting, there remains a paucity of suitable animal models for studying PONV. Prior studies have been confined to anatomical and pharmacological investigations, while research on the molecular, cellular, and neural circuit mechanisms of post-thyroidectomy PONV remains scarce. In the existing research, some scientists have defined the behavior of mice opening their mouths as the occurrence of nausea and vomiting in mice. Here, we aim to establish a rodent model of thyroidectomy-induced retching-like behavior (TIRB) in mice to mimic PONV, thereby enabling systematic characterization of its neural and molecular regulatory pathways.</div></div><div><h3>Methods</h3><div>In this study, a mouse model of retching-like behavior was established using thyroidectomy. Using transcriptomics, we explored the up-regulated genes after TIRB, focusing on finding feasible targets for TIRB treatment. Meanwhile, we used immunofluorescence and qPCR to verify the expression of up-regulated genes.</div></div><div><h3>Results</h3><div>Our screening revealed that IL-1β, an inflammatory factor associated with NLRP3, was significantly up-regulated after TIRB. In addition, immunofluorescence revealed a significant increase in NLRP3 expression in area postrema, and treatment with MCC950, a specific NLRP3 inhibitor, decreased retching-like behavior incidence in mice.</div></div><div><h3>Conclusion</h3><div>These results suggest that NLRP3-related molecular pathways may be closely related to TIRB occurrence. NLRP3 could be a novel treatment target of TIRB.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"165 ","pages":"Article 115541"},"PeriodicalIF":4.7,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cucurbitacin B suppresses malignant progression of oral leukoplakia via ferroptosis-induced macrophage polarization","authors":"Chen Cheng ,&nbsp;Jiawei Chai ,&nbsp;Heng Zhang ,&nbsp;Yajun Wang ,&nbsp;Lin Zhang ,&nbsp;Mengyuan Yang ,&nbsp;Xin Chen ,&nbsp;Qi Jiang ,&nbsp;Hui Ren ,&nbsp;YaHsin Cheng ,&nbsp;Fang Zhang","doi":"10.1016/j.intimp.2025.115485","DOIUrl":"10.1016/j.intimp.2025.115485","url":null,"abstract":"<div><div>M2 macrophage, which can promote oral leukoplakia (OLK) development and progression, is considered a new potential target for the treatment and prevention of OLK malignant progression. Cucurbitacin B (CuB), a tetracyclic triterpenoid compound widely found in cucurbit plants, has shown promising immunomodulatory and anti-proliferative efficacy in previous studies. However, whether CuB can inhibit OLK malignant progression by modulating M2 macrophage polarization remains unclear. This study aims to investigate the role of CuB in regulating M2 macrophage polarization in inhibiting the malignant progression of OLK and further explore its potential mechanism of action. In vivo experiments showed that CuB significantly inhibited 4NQO-induced malignant progression of OLK to oral squamous cell carcinoma (OSCC) in C57BL/6 mice. In mice OLK tissues, CuB decreased the number of M2 macrophages but increased the number of M1 macrophages. Bioinformatics and in vitro experiments showed that CuB appears to activate ferroptosis in M2 macrophages by promoting Fe²⁺ accumulation, down-regulating GPX4 and SLC7A11, and up-regulating COX-2 expression. The resulting ferroptosis products, including MDA, ROS, and LPO, may contribute to the remodeling of M2 macrophages into an M1 phenotype. Furthermore, in vitro indirect co-culture experiments indicate that CuB-activated ferroptosis in M2 macrophages significantly inhibited the proliferation of dysplastic oral keratinocyte (DOK) cells. In conclusion, CuB can inhibit the malignant progression of OLK, and ferroptosis-induced macrophage polarization may play a key role in this process. This study provides new insights into the application of CuB in the immunotherapy of OLK.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"165 ","pages":"Article 115485"},"PeriodicalIF":4.7,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting GCS regulates the NRF2 axis to inhibit hepatocyte endoplasmic reticulum stress-ferroptosis improving immune-mediated liver injury","authors":"Zibing Qian ,&nbsp;Junfeng Li ,&nbsp;Xiaorong Mao ,&nbsp;Jian Gan ,&nbsp;Aipin Tian ,&nbsp;Xuebin Peng","doi":"10.1016/j.intimp.2025.115532","DOIUrl":"10.1016/j.intimp.2025.115532","url":null,"abstract":"<div><h3>Background</h3><div>Ferroptosis is a regulated, iron-dependent form of cell death triggered by toxic accumulation of lipid peroxides on cell membranes. Although it is established that glycosphingoid metabolites can activate the ferroptosis signaling pathway, whether they are involved in regulating endoplasmic reticulum stress (ERS)-ferroptosis in immune-mediated liver injury requires further investigation.</div></div><div><h3>Methods</h3><div>This study used the GCS inhibitor GENZ-123346 (GENZ) to treat ConA-induced immune liver injury in mice. Inflammatory factor levels and liver histology were analyzed to evaluate GENZ's effects. Additionally, the antioxidant and lipid peroxidation capacity of GENZ was tested in vivo and in vitro. Based on the regulation of NFE2-related factor 2 (NRF2) signaling pathway expression (including si-NRF2, NRF2 inducer sulforaphane (SFN), and inhibitor ML385), the regulatory effect of GENZ on ERS-ferroptosis was investigated.</div></div><div><h3>Results</h3><div>GENZ administration improved the survival rate of mice with immune-mediated liver injury, decreased serum transaminase activity, inhibited inflammatory factor production, reduced hepatocyte ferroptosis. In in vitro experiments, ferroptosis in AML12 cells was accompanied by the activation of ERS-related proteins Glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and mild alterations in endoplasmic reticulum ultrastructure. Inhibition of ERS by 4-phenylbutyric acid (4-PBA) attenuated ferroptosis in AML12 cells. However, when the cells were treated with the ferroptosis inducer RSL3 in combination with the ERS inducer thapsigargin (Tg), GENZ could not effectively suppress ferroptosis. Silencing NRF2 exacerbated cellular ferroptosis and ERS while diminishing the expression of downstream effectors heme oxygenase-1 (HO-1) and NAD(<em>P</em>)H quinone oxidoreductase 1 (NQO1). Conversely, SFN treatment alleviated these effects and upregulated NRF2 signaling, increasing HO-1 and NQO1 expression. Furthermore, ML385 administration reversed the hepatoprotective and antioxidant effects of GENZ on immune-mediated liver injury in mice.</div></div><div><h3>Conclusions</h3><div>GCS inhibition exerts hepatoprotective effects by modulating the NRF2 antioxidant pathway to suppress ERS and hepatocyte ferroptosis, revealing a novel role of glycosphingolipid metabolism in immune-mediated liver injury and programmed hepatocyte death.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"165 ","pages":"Article 115532"},"PeriodicalIF":4.7,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the gut microbiota alterations and their correlation with cytokine gene expression in patients with ankylosing spondylitis","authors":"Saeedeh Farsadi ,&nbsp;Yaeghob Sharifi ,&nbsp;Morteza Bagheri ,&nbsp;Mir Amir Aghdashi","doi":"10.1016/j.intimp.2025.115534","DOIUrl":"10.1016/j.intimp.2025.115534","url":null,"abstract":"<div><h3>Purpose</h3><div>Ankylosing spondylitis (AS) is a common form of spondyloarthritis, recognized as a chronic autoimmune disorder with an unclear etiology. This study aimed to investigate changes in the intestinal microbiota, (<em>Bifidobacterium</em> sp., <em>Bacteroides</em> sp., <em>Clostridium leptum</em>, and <em>Enterobacteriaceae</em>) and to explore their relationship with cytokine gene expression in patients with AS attending a rheumatology clinic or admitted to the rheumatology ward of Imam Khomeini Hospital in Urmia, Iran.</div></div><div><h3>Methods</h3><div>This investigation involved a cohort of twenty patients diagnosed with AS alongside a control group of twenty healthy individuals matched for age and sex. Fecal specimens were collected to extract DNA, which was subsequently analyzed for the characterization of the gut microbiome via PCR and quantitative real-time PCR. Furthermore, RNA obtained from peripheral blood mononuclear cells was analyzed to quantify the expression of pro-inflammatory cytokines as well as anti-inflammatory cytokines using qPCR.</div></div><div><h3>Results</h3><div>The analysis revealed that the bacterial load of <em>Enterobacteriaceae</em>, <em>Bacteroides</em> and <em>Bifidobacterium</em> were markedly elevated in the patients than in the control group (<em>P</em> &lt; 0.05). The relative amount of TNF-α, IL-17F, IL-17 A, and INF-γ were significantly increased in patients group compared to controls (<em>P</em> &lt; 0.05). But, the relative amount of TGF-β was significantly reduced in AS patients compared with controls (<em>P</em> <em>=</em> 0.03).</div></div><div><h3>Conclusion</h3><div>To conclude, an imbalance was observed in the dominant intestinal microbiota in AS patients, leading to a shift in the microbiota towards the production and secretion of inflammatory cytokines, as well as a reduction in anti-inflammatory cytokines, thereby playing a critical role in the pathogenesis of AS disease.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"165 ","pages":"Article 115534"},"PeriodicalIF":4.7,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential modulation of microglial ferroptosis by Linggui Zhugan decoction in Alzheimer's disease through IL-17 and TNF pathways","authors":"Peng Tang ,&nbsp;Danjie Zhao ,&nbsp;Haixia Lin ,&nbsp;Xia Li ,&nbsp;Chongjing Shi ,&nbsp;Ping Li ,&nbsp;Huibin Chen","doi":"10.1016/j.intimp.2025.115489","DOIUrl":"10.1016/j.intimp.2025.115489","url":null,"abstract":"<div><div>Alzheimer's Disease (AD) is a neurodegenerative condition marked by cognitive decline and memory loss, with ferroptosis, an iron-dependent form of regulated cell death, emerging as a contributing factor. This study explored the potential modulatory effects of key components of the traditional Chinese medicine (TCM) formula Linggui Zhugan Decoction (LZD) on microglial ferroptosis in AD, focusing on IL-17 and TNF signaling pathways. Using single-cell RNA sequencing, we observed alterations in microglial populations and ferroptosis-related gene expression in AD mice. Network pharmacology and in vitro experiments indicated that LZD components might influence ferroptosis-related pathways, coinciding with reduced IL-17 and TNF levels in Aβ1–42-treated microglia. In vivo, LZD administration was associated with improved behavioral outcomes and modulation of ferroptosis markers. Although our findings suggest a correlation between LZD treatment and attenuation of ferroptosis-associated pathology, further mechanistic validation is necessary to establish causal links. This study provides preliminary evidence supporting the therapeutic potential of TCM in AD via inflammatory pathway modulation.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"165 ","pages":"Article 115489"},"PeriodicalIF":4.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional antibacterial micelle with targeting ability and lipase-responsibility for therapy of methicillin-resistant Staphylococcus aureus infection","authors":"Hua Chun ,&nbsp;Shuo Wang ,&nbsp;Qinrong Shi ,&nbsp;Aga Erbu ,&nbsp;Bengui Ye ,&nbsp;Hongjun Xie","doi":"10.1016/j.intimp.2025.115499","DOIUrl":"10.1016/j.intimp.2025.115499","url":null,"abstract":"<div><div>Bacterial infections frequently trigger severe inflammatory cascades accompanied by oxidative stress responses, which collectively impair tissue regeneration and exacerbate disease progression. Consequently, there is a pressing clinical need to develop therapeutic strategies capable of simultaneously eradicating pathogenic bacteria and modulating the infection microenvironment. The infected tissue microenvironment is characterized by macrophage infiltration and upregulation of folate receptor expression on their cellular surfaces. Concurrently, pathogenic bacteria actively secrete abundant lipase at the site of infection. In this study, we developed an infection-targeting nano-micelle system with lipase-responsive drug release capabilities (FA/AC-M)，which were self-assembled from TPGS and DSPE-PEG₂₀₀₀, with folic acid (FA) modification on the surface. The ester group in DSPE-PEG₂₀₀₀ was sensitive to lipase. FA/AC-M was found to possess uniform size, smooth morphology, satisfactory stability and encapsulation efficiency. The encapsulated Ampicillin and Curcumin exhibited synergistic antibacterial effect evidenced by Synergy Finder analysis. <em>In vitro</em>, FA/AC-M could effectively change bacterial membrane permeability, result in protein leakage, inactivate planktonic bacteria, inhibit biofilm formation and reduce intracellular bacterial burden. Additionally, FA/AC-M selectively targeted inflamed RAW 264.7 cells and bacterial infection sites, demonstrated by <em>in vivo</em> and <em>in vitro</em> studies. Besides, the incorporation of Cur into FA/AC-M achieved significant enhancement of immunomodulatory activity and antioxidant capacity. <em>In vivo</em> evaluation using a methicillin-resistant <em>Staphylococcus aureus</em> (MRSA)-infected murine thigh muscle model demonstrated that:FA/AC-M remarkably reduced bacterial counts at the infection site, alleviated inflammatory responses, prompted M2 polarization of macrophage. Therefore, FA/AC-M provides a promising therapeutic approach for the treatment of MRSA infections.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"165 ","pages":"Article 115499"},"PeriodicalIF":4.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helixor A enhances natural killer cell activity by induction of PAI-1 expression through the p38/MAPK signaling pathway","authors":"Yunhee Lee ,&nbsp;Mi Jeong Kim ,&nbsp;Young-Ju Kang ,&nbsp;In cheul Jeung ,&nbsp;Haiyoung Jung ,&nbsp;Tae-Don Kim ,&nbsp;Ji-Yoon Noh ,&nbsp;Inpyo Choi ,&nbsp;Suk Ran Yoon","doi":"10.1016/j.intimp.2025.115531","DOIUrl":"10.1016/j.intimp.2025.115531","url":null,"abstract":"<div><div>Helixor A, an anticancer drug, has an immunostimulatory effect that increases T and natural killer (NK) cell activity in patients with cancer and endometriosis. However, the molecular mechanisms underlying its effect on NK cells in these patients are not fully understood. In this study, we investigated the effect of helixor A on the activation and differentiation of NK cells, and elucidated the underlying mechanisms. Helixor A enhanced the cytotoxic activity of NK cells in a dose-dependent manner and simultaneously increased the expression of NK-activating receptors, particularly NKp44 and NKp30. It also increased the expression of cytolytic granules, such as granzyme B and perforin, as well as the expression of CD107a, a marker of NK cell degranulation. In addition, the production of IFN-γ and TNF-α was increased in NK cells. However, helixor A did not significantly affect the differentiation of NK cells from CD34⁺ hematopoietic cells. Mechanistically, helixor A activated the p38/MAPK pathway and upregulates PAI-1 expression. Inhibition of the p38 pathway abolished helixor A-induced upregulation of cytotoxic activity and PAI-1 expression in NK cells. In addition, PAI-1 overexpression in NK cells increased cytotoxicity against target cells and p38 phosphorylation. Furthermore, a PAI-1 promoter assay showed that p38 increased PAI-1 transcriptional activity. It was also confirmed that p38 interacts with PAI-1, and this interaction is increased by helixor A treatment in NK cells. Collectively, helixor A may serve as a therapeutic agent to increase NK cell cytotoxicity or transduction of PAI-1 in NK cells can be transplanted as a gene therapy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"165 ","pages":"Article 115531"},"PeriodicalIF":4.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactuca indica L. polysaccharide ameliorates type 1 diabetes via gut microbiota-SCFAs-IRS-1/PI3K/GLUT4-MYD88/NF-κB axis","authors":"Yan Zhang ,&nbsp;Huiying Zhang ,&nbsp;Ruoqi Wang,&nbsp;Jing Shi,&nbsp;Hui Wang,&nbsp;Jiaqi Gao,&nbsp;Qin Ge,&nbsp;Jiaxin Han","doi":"10.1016/j.intimp.2025.115536","DOIUrl":"10.1016/j.intimp.2025.115536","url":null,"abstract":"<div><div><em>Lactuca indica</em> L. is both edible and medicinal, and has various effects such as antioxidant and anticardiovascular diseases. <em>Lactuca indica</em> L. polysaccharide (LIP) is the active constituent of <em>Lactuca indica</em> L. The goal of this study was to provide a preliminary analysis of the structural properties of LIP and to investigate its therapeutic efficacy and possible mechanisms in STZ-induced T1DM. This study isolated a homogeneous polysaccharide, designated LIP, from the crude polysaccharide of <em>Lactuca indica</em> L. This polysaccharide is an acidic polysaccharide consisting of eight monosaccharides. LIP has significant therapeutic effects on T1DM mice, can regulate abnormal glucose metabolism, inhibit excessive inflammation, and alleviate pancreatic and hepatic damage. Furthermore, LIP modulated hepatic insulin signaling and inflammatory pathways, as well as restored the balance of the intestinal microbiota, particularly with regard to the increase in SCFAs-producing bacteria. There is a significant correlation among them. In conclusion, LIP may be a candidate agent to treat diabetes.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"165 ","pages":"Article 115536"},"PeriodicalIF":4.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemicals from Stellera chamaejasme alleviate psoriasis by modulating the immune microenvironment via the JAK2/PI3K/AKT pathway","authors":"Ruo-Fan Xi ,&nbsp;Yi-Wen Nie ,&nbsp;Han-Zhi Lu ,&nbsp;Xin Liu ,&nbsp;Zhi-Guang Feng ,&nbsp;Yi Wang ,&nbsp;Dong-Jie Guo ,&nbsp;Wan-Jun Guo ,&nbsp;Hua Nian ,&nbsp;Fu-Lun Li ,&nbsp;Jian-Yong Zhu","doi":"10.1016/j.intimp.2025.115540","DOIUrl":"10.1016/j.intimp.2025.115540","url":null,"abstract":"<div><div><em>Stellera chamaejasme</em> L., a traditional Chinese medicinal herb used for treating skin disorders such as psoriasis, was investigated to identify its bioactive antipsoriatic components and elucidate its underlying mechanisms of action. In an imiquimod (IMQ)-induced psoriasis-like skin lesion mouse model, the ethyl acetate (Et) fraction exhibited the most significant therapeutic effect among various solvent-partitioned extracts, as demonstrated by hematoxylin-eosin (H&amp;E), immunohistochemistry (IHC), and immunofluorescence (IF) analyses. The bioassay-guided fractionation of the Et extract led to the isolation of eleven compounds (<strong>1</strong>−<strong>11</strong>), whose structures were characterized using nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography. Among them, wikstroelide J (WJ, compound <strong>11</strong>) exhibited the most potent activity, inhibiting M5-induced hyperproliferation of HaCaT keratinocytes (IC₅₀ = 9.4 μM) and alleviating psoriasis-like skin lesions <em>in vivo</em>. Mechanistically, WJ modulated T-cell subsets and downregulated the JAK2/PI3K/AKT signaling pathway, with pathway involvement further supported by the use of the JAK2 inhibitor AG490. These findings highlight WJ as a promising antipsoriatic agent that targets the JAK2/PI3K/AKT pathway. Future studies will aim to improve its pharmacological properties and assess its efficacy in clinical settings, although current limitations, such as a lack of pharmacokinetic and clinical data, remain to be addressed.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"165 ","pages":"Article 115540"},"PeriodicalIF":4.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}