International immunopharmacology最新文献

{"title":"Structural polysaccharide PCP1 from Polygonatum cyrtonema Hua attenuates atherosclerosis via dual-target suppression of CD36/MSR1 and TLR4/NF-κB pathways","authors":"Lutan Zhou ,&nbsp;Xinya Zhao ,&nbsp;Zhu Yang ,&nbsp;Chenchen Jiang ,&nbsp;Huaizheng Song ,&nbsp;Wei Liu ,&nbsp;Guodong Wang ,&nbsp;Hui Che ,&nbsp;Jun Han","doi":"10.1016/j.intimp.2025.115644","DOIUrl":"10.1016/j.intimp.2025.115644","url":null,"abstract":"<div><div>Atherosclerosis, a chronic inflammatory disease, is characterized by lipid accumulation and inflammation in arterial walls. <em>Polygonatum cyrtonema</em> Hua, a traditional Chinese medicine and functional food, has long been used to treat cardiovascular diseases. In this study, we investigated the effects of a purified polysaccharide component (PCP1) from <em>P. cyrtonema</em> Hua on atherosclerosis. <em>In vitro</em>, the influence of PCP1 on lipid accumulation and inflammation in macrophages was assessed. <em>In vivo</em>, ApoE^−/− mice fed a high-fat diet (HFD) for 12 weeks were treated with PCP1 <em>via</em> daily gavage. Subsequently, lipid levels, inflammatory markers, and atherosclerotic lesion development were evaluated. The results demonstrated that PCP1 significantly ameliorated atherosclerosis by inhibiting macrophage lipid accumulation and inflammation. Mechanistically, PCP1 downregulated CD36 and MSR1, which are involved in lipid uptake and reduced the expression of pro-inflammatory cytokines by blocking the TLR4/NF-κB signaling. Additionally, PCP1 mitigated the overactivation of aortic endothelial cells and suppressed inflammatory responses in smooth muscle cells. Overall, PCP1 uniquely exerted anti-atherosclerotic effects through dual modulation of lipid metabolism and inflammation, thereby validating its traditional use in cardiovascular conditions and highlighting its potential as a therapeutic agent.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115644"},"PeriodicalIF":4.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217775","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":"Questions on the mechanistic scope and clinical applicability of Kanglexin in hepatic fibrosis","authors":"Parth Aphale ,&nbsp;Shashank Dokania ,&nbsp;Himanshu Shekhar","doi":"10.1016/j.intimp.2025.115626","DOIUrl":"10.1016/j.intimp.2025.115626","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115626"},"PeriodicalIF":4.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217778","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":"Emerging role of Itaconate in inflammatory bowel disease: From multitarget Immunometabolic mechanisms to therapeutic translation","authors":"Mei Kang ,&nbsp;Daiyuan Tang ,&nbsp;Wei Huang ,&nbsp;Mingxia Zhou ,&nbsp;Qiang Ma ,&nbsp;Yining Lan ,&nbsp;Deyi Chen ,&nbsp;Ya Li ,&nbsp;Bing Han","doi":"10.1016/j.intimp.2025.115632","DOIUrl":"10.1016/j.intimp.2025.115632","url":null,"abstract":"<div><div>Itaconate (ITA), as an emerging immunometabolite, has been proven to play a significant protective role in inflammatory diseases like systemic lupus erythematosus, rheumatoid arthritis, and atherosclerosis in recent years. However, its comprehensive regulatory mechanisms and therapeutic potential in inflammatory bowel disease (IBD) remain underexplored. This review focuses on the metabolism-immune regulatory functions of ITA in IBD, elucidating its multi-target mechanisms: reducing the tissue infiltration of innate immune cells; promote the anti-inflammatory phenotypic transformation of M2 in macrophages; inhibit the production of key pro-inflammatory factors; enhance the intestinal epithelial barrier function; and modulating gut microbiota composition and host-microbiota crosstalk. Building upon this mechanistic foundation, this review further explores the potential of ITA as a novel therapeutic strategy for IBD, including its application prospects as a monotherapy, synergistic effects with other existing drugs, and the feasibility of targeting the ITA metabolic pathway as a future drug development direction. In conclusion, it is of paramount to deeply clarify the precise actions of ITA within the complex microenvironment of IBD, which can accelerate the advancement of rigorous clinical research, overcome the current challenges in IBD treatment, and ultimately provide patients with a new option for safer and more effective metabolic immunotherapy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115632"},"PeriodicalIF":4.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217828","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":"Tubuloside B alleviates con A-induced acute liver injury by inhibiting the IL-23/JAK2/STAT3 signaling pathway hyperactivation during Th17 cell differentiation","authors":"Jing Luo ,&nbsp;Zhe Yu ,&nbsp;Wen An ,&nbsp;Mengqi Li ,&nbsp;Herui Wei ,&nbsp;Ziteng Wang ,&nbsp;Lingling He ,&nbsp;Fan Xiao ,&nbsp;Hongshan Wei","doi":"10.1016/j.intimp.2025.115586","DOIUrl":"10.1016/j.intimp.2025.115586","url":null,"abstract":"<div><h3>Background</h3><div>Tubuloside B (TB), a phenylethanoid glycoside from Cistanche salsa, has been reported to exhibit anti-inflammatory and anti-HCC properties; however, its therapeutic efficacy and underlying mechanisms in concanavalin A (Con A)-induced liver injury remain unclear.</div></div><div><h3>Methods</h3><div>We employed a Con A-induced acute liver injury (ALI) mouse model and in vitro Th17 differentiation assays were employed to investigate the therapeutic potential and mechanisms of TB through serum biochemistry, histopathology, flow cytometry, RNA sequencing, qPCR, and Western blotting (WB).</div></div><div><h3>Results</h3><div>TB significantly reduced Con A-induced elevations in serum ALT/AST levels, ameliorated hepatic necrosis and inflammatory infiltration, and suppressed pro-inflammatory cytokines in vivo. RNA-seq and pathway analysis revealed that TB inhibited the IL-17A signaling pathway and restored the Th17/Treg balance by reducing Th17 cell proportions (CD4⁺IL-17A⁺ and CD4⁺RORγt⁺) while increasing Treg proportions (CD25⁺Foxp3⁺). Mechanistically, TB inhibited IL-17A-driven activation of NF-κB and MAPK pathways in the liver. Furthermore, molecular docking and in vitro Th17 differentiation assays demonstrated that TB directly targeted IL-23R (ΔG = −10.9 kcal/mol), suppressed IL-23-induced overactivation of the JAK2/STAT3 pathway (p-JAK2, p-STAT3), and inhibited pathogenic Th17 differentiation.</div></div><div><h3>Conclusions</h3><div>Collectively, our findings demonstrate that TB alleviates Con A-induced ALI by blocking the IL-23/JAK2/STAT3 signaling axis during Th17 cell differentiation, thereby attenuating IL-17-mediated hepatic inflammation. This study highlights TB as a potential natural therapeutic candidate for ALI and suggests its potential application in mitigating autoimmune hepatitis (AIH) progression.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115586"},"PeriodicalIF":4.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217872","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":"GPR75 knockdown alleviates mitochondrial dysfunction in hippocampal neurons via AMPK pathway in diabetic mice","authors":"Mengren Liu ,&nbsp;Lihua Liu ,&nbsp;Wenqiang Liu ,&nbsp;HongDan Yu ,&nbsp;Shengxue Yu ,&nbsp;Zihao Liu ,&nbsp;Yali Wang ,&nbsp;Xinyuan Chen ,&nbsp;Quanling Miao ,&nbsp;Yirong Yuan ,&nbsp;Wei Dai ,&nbsp;Jiawei Hu ,&nbsp;Na Zhang ,&nbsp;Jiaheng Sui ,&nbsp;Xuezheng Liu ,&nbsp;Zhongfu Zuo","doi":"10.1016/j.intimp.2025.115638","DOIUrl":"10.1016/j.intimp.2025.115638","url":null,"abstract":"<div><div>Diabetic cognitive dysfunction (DCD) is widely acknowledged as a cerebral complication of diabetes mellitus involving hippocampal neuronal damage caused by mitochondrial dysfunction. G protein-coupled receptor 75 (GPR75) is an orphan receptor associated with inflammation, mitochondrial function, and metabolic disorders. However, its exact role in DCD has not yet been reported. In order to investigate the effect of GPR75 on DCD, we employed streptozotocin (STZ)-treated C57BL/6 J mice and high glucose (HG)-treated mouse hippocampal neuronal cells (HT22). Our investigations revealed upregulation of GPR75 in DCD. Furthermore, we demonstrated that knocking down GPR75 could mitigate the progression of DCD, with its protective effects associated with the inhibition of mitochondrial dysfunction in hippocampal neurons. AMP-activated protein kinase (AMPK), a regulator of mitochondrial function and cellular energy sensor, was identified as a novel target for GPR75. Immunofluorescence and co-immunoprecipitation (CO-IP) analyses confirmed the co-localization and interaction between GPR75 and AMPK in HT22 cells. Mechanistically, the upregulation of GPR75 inhibits AMPK-mediated mitochondrial homeostasis, resulting in impaired mitochondrial dynamics, disrupted energy metabolism, and elevated reactive oxygen species (ROS), which ultimately triggers pyroptosis and apoptosis in hippocampal neurons. Notably, the AMPK-activator AICAR mitigates GPR75-induced mitochondrial dysfunction, pyroptosis, and apoptosis. In summary, our findings suggest that targeted inhibition of GPR75 may represent a promising therapeutic strategy for DCD.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115638"},"PeriodicalIF":4.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217776","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":"Experimental investigation of adipose-derived mesenchymal stem cell-derived exosomes in the treatment of osteoporosis via the hsa_circ_0028877/miR-4728-3p/PTCH1 axis","authors":"Jianqiao Li,&nbsp;Qingsong Gu,&nbsp;Yiheng Li,&nbsp;Yifan Gu,&nbsp;Yuhu Chen,&nbsp;Linhui Wang,&nbsp;Ziru Wang,&nbsp;Yicong Wang,&nbsp;Min Yang","doi":"10.1016/j.intimp.2025.115625","DOIUrl":"10.1016/j.intimp.2025.115625","url":null,"abstract":"<div><h3>Background</h3><div>hsa_circ_0028877 may serve as a biomarker for postmenopausal osteoporosis (PMOP) based on bioinformatics analysis; nevertheless, the underlying mechanism remains ambiguous. ADSCs-derived exosomes (ADSCs-exos), as an innovative cell-free therapeutic agent that influences numerous biological processes, including immunological modulation, reduction of oxidative damage, and enhancement of tissue repair and regeneration.</div></div><div><h3>Objective</h3><div>In vitro experiments were performed to evaluate the impact of hsa_circ_0028877 on cellular proliferation, osteogenic differentiation, and osteoclast differentiation. The study examined the regulatory function of ADSCs-exos on the hsa_circ_0028877/miR-4728-3p/PTCH1 axis and its therapeutic implications for osteoporosis.</div></div><div><h3>Methods</h3><div>The ovariectomised rat (OVX) model was employed to simulate PMOP. The impact of hsa_circ_0028877 overexpression and knockdown on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were examined. The RNA immunoprecipitation (RIP) method was employed to validate the connection among hsa_circ_0028877, miR-4728-3p, and PTCH1. ADSCs-exos modulate their downstream molecular pathway by obstructing the nuclear transport of hsa_circ_0028877. The impact of ADSCs-exos on bone mass, trabecular microstructure, and the mineralization capacity of BMSCs was evaluated in a rat model.</div></div><div><h3>Results</h3><div>hsa_circ_0028877 is significantly expressed in ovariectomised rat BMSCs. hsa_circ_0028877 enhances PTCH1 expression through its interaction with miR-4728-3p. ADSCs-exos can rehabilitate bone mass in the distal femur of ovariectomised rats. ADSCs-exos facilitate osteogenesis by obstructing the nuclear export of hsa_circ_0028877, significantly boosting trabecular microstructure and mineralization in the BMSCs of ovariectomised rats.</div></div><div><h3>Conclusion</h3><div>ADSCs-exos promote osteogenic differentiation and bone formation in BMSCs by obstructing the nuclear export of hsa_circ_0028877 and modulating the hsa_circ_0028877/miR-4728-3p/PTCH1 axis, thereby improving PMOP.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115625"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212483","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":"Astragalus polysaccharide enhances OGT-mediated O-GlcNAcylation to stabilize PINK1 to induce mitophagy in D-galactose treated C2C12 myoblasts","authors":"Deqing Chen ,&nbsp;Zijin Qiu ,&nbsp;Yongxin Wu ,&nbsp;Yingxiao Zhang ,&nbsp;Huanhuan Huang ,&nbsp;Hailing Yang ,&nbsp;Qian Xiao","doi":"10.1016/j.intimp.2025.115617","DOIUrl":"10.1016/j.intimp.2025.115617","url":null,"abstract":"<div><h3>Background</h3><div>Astragalus polysaccharide (APS) has been shown to alleviate muscle atrophy. This study investigated the effects and underlying mechanisms of APS on D-galactose (D-gal)-induced mitochondrial autophagy in C2C12 myoblasts.</div></div><div><h3>Methods</h3><div>Cell viability in C2C12 myoblasts was assessed using the CCK-8 assay. To further elucidate the role of APS, we evaluated skeletal muscle cell diameter and mitochondrial autophagy in C2C12 myoblasts, with and without O-GlcNAc transferase (OGT). Immunofluorescence staining for myosin heavy chain (MyHC) and western blot analysis were employed. Co-immunoprecipitation (Co-IP) experiments and immunofluorescence staining were conducted to examine the interaction between OGT and PTEN-induced putative kinase 1 (PINK1). In vivo, male C57BL/6 J mice were treated with D-gal to induce sarcopenia, and APS was administered to assess its effects on muscle function and mitochondrial health.</div></div><div><h3>Results</h3><div>APS promoted mitophagy in vitro by inducing O-GlcNAcylation through OGT. Knockdown of OGT significantly weakened the protective effects of APS. OGT modifies PINK1 with O-GlcNAcylation through the S425 site. In vivo, APS treatment significantly improved grip strength and muscle mass in D-gal-induced sarcopenia mice. Histological analysis showed increased cross-sectional area of gastrocnemius muscle fibers, and Western blot analysis revealed enhanced expression of LC3II, PINK1, and Parkin in muscle tissues.</div></div><div><h3>Conclusion</h3><div>Collectively, APS promotes OGT-mediated O-GlcNAcylation to stabilize PINK1, thereby facilitating mitophagy in D-gal-treated C2C12 myoblasts in vitro. In vivo, APS improves muscle function and mitochondrial health in a mouse model of sarcopenia. These findings suggest that APS could serve as a potential therapeutic agent for muscle atrophy and related conditions.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115617"},"PeriodicalIF":4.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212530","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":"Therapeutic potential of polysaccharides in inflammation: current insights and future directions","authors":"Thananjeyan Balasubramaniyam ,&nbsp;Hye-Bin Ahn ,&nbsp;Juhee Lim ,&nbsp;Abhishikta Basu ,&nbsp;Jacek Z. Kubiak ,&nbsp;Shailima Rampogu ,&nbsp;Vinod Kumar Nathan","doi":"10.1016/j.intimp.2025.115538","DOIUrl":"10.1016/j.intimp.2025.115538","url":null,"abstract":"<div><div>Polysaccharides from plants, microorganisms, algae, and animals exhibit significant anti-inflammatory potential, offering safe and effective therapeutic options for diseases like inflammatory bowel disease and arthritis. This review synthesizes their sources, structural modifications, and mechanisms, including modulation of NF-κB and MAPK pathways. In vitro models (e.g., RAW264.7 macrophages, THP-1 cells) demonstrate reductions in pro-inflammatory cytokines (e.g., TNF-α and IL-1β by 30–40 % at doses of 50–200 μg/mL), while in vivo models (e.g., DSS-induced colitis, collagen-induced arthritis) show decreased Disease Activity Index and improved histopathological outcomes at doses of 50–200 mg/kg. Chemical modifications, such as sulfation, enhance bioactivity, though challenges like bioavailability, inconsistent methodologies, and variable dosing persist. A comprehensive Table 3 summarizes sources, compounds, models, doses, and effects, while critical evaluations highlight methodological limitations and propose standardized assays (e.g., ELISA, qPCR). Future directions include nanotechnology for improved delivery, bioinformatics for structural optimization, and randomized clinical trials to validate preclinical findings, paving the way for novel polysaccharide-based therapies.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115538"},"PeriodicalIF":4.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206352","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":"Engineering scFv immunotherapies: From CAR T cells to bispecific antibodies","authors":"Mohammad Chand Jamali ,&nbsp;Amged Gaffer Mostafa Gaffer ,&nbsp;Hakeem Ghani Hassan ,&nbsp;Sana Abdul-Jabbar Ali ,&nbsp;Mahaboob Khan Sulaiman ,&nbsp;Anam Tariq ,&nbsp;Nasrin Mansuri ,&nbsp;Ashit Kumar Dutta ,&nbsp;Mustafa Mudhafar","doi":"10.1016/j.intimp.2025.115597","DOIUrl":"10.1016/j.intimp.2025.115597","url":null,"abstract":"<div><div>Single-chain variable fragments (scFvs) have become indispensable tools in cancer immunotherapy due to their high specificity, modularity, and cost-effective production. These engineered antibody fragments enable precise targeting of tumor antigens, driving innovations in chimeric antigen receptor (CAR) T cell therapy, bispecific T-cell engagers, immune checkpoint blockade, and nanoparticle delivery systems. Their compact size enhances tumor penetration compared to full-length antibodies, while recombinant production allows rapid customization. This review examines the expanding therapeutic applications of scFvs across multiple modalities, including their critical role in CAR-T cell engineering where scFv affinity determines efficacy and safety. We explore bispecific engagers that redirect T cells to tumors, checkpoint inhibitors that restore antitumor immunity, and targeted drug delivery platforms. Clinical successes in hematologic malignancies are highlighted alongside ongoing challenges in solid tumors, particularly regarding antigen heterogeneity and immunosuppressive microenvironments. Key advances in scFv optimization are discussed, focusing on half-life extension strategies, stability engineering, and combinatorial approaches to overcome limitations like rapid clearance and on-target/off-tumor toxicity. By synthesizing recent preclinical and clinical developments, this review demonstrates how scFv-based therapies continue to transform precision oncology through targeted immune modulation.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115597"},"PeriodicalIF":4.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199163","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":"Polyphyllin I induces pyroptosis in diffuse large B-cell lymphoma by activating the caspase-6/ZBP1/NLRP3 signaling pathway","authors":"Yulian Liu ,&nbsp;Mengyue Fan ,&nbsp;Yuanxin Chen ,&nbsp;Chuanmin Zhang ,&nbsp;Lijuan Wang ,&nbsp;Yao Fu","doi":"10.1016/j.intimp.2025.115592","DOIUrl":"10.1016/j.intimp.2025.115592","url":null,"abstract":"<div><div>Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive and heterogeneous hematological malignancy of B-cell origin, commonly observe in clinical practice. Chemotherapy resistance poses a significant challenge to DLBCL treatment, necessitating novel therapies. Polyphyllin I (PPI) exhibits anticancer effects on various cancer cells, but its impact on DLBCL remains unclear. This study investigated the mechanism underlying PPI in treating DLBCL, specifically focusing on the caspase-6/ZBP1/NLRP3 pathway involved in pyroptosis and apoptosis. The role caspase-6 plays in regulating pyroptosis is unknown. We hypothesized PPI activates this pathway, triggering tumor cell death. Through both in vitro and in vivo experiments, we found that PPI significantly promoted DLBCL cell pyroptosis and apoptosis by activating the caspase-6/ZBP1/NLRP3 pathway. These findings suggest that the caspase-6 pathway has the potential to be developed as a novel treatment for DLBCL. Further research is needed to explore the clinical application of PPI in lymphoma treatment and its potential synergies with other drugs.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115592"},"PeriodicalIF":4.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199107","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}