International immunopharmacology最新文献

{"title":"Expression of concern: \"Integrating network pharmacology and animal experimental validation to investigate the mechanism of lotus leaf in obesity\" [Int. Immunopharmacol. 145 (2025) 113719].","authors":"Haojing Li, Wenli Li, Yuanyuan Wu, Huimin Wu, Xiaojun Cai","doi":"10.1016/j.intimp.2026.117017","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117017","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"185 ","pages":"117017"},"PeriodicalIF":5.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470387","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":"MSTO1 promotes hepatocellular carcinoma progression and represents a potential target for immunotherapy.","authors":"Xiangdong Li, Haoliang Zhu, Minhao Chen, Chuanwei Jiang, Wenjie Yu, Yuhao Xiao, Jie Wei, Xiangyu Li, Chenyu Jiao, Sheng Han, Liyong Pu","doi":"10.1016/j.intimp.2026.117358","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117358","url":null,"abstract":"<p><p>The incidence of hepatocellular carcinoma (HCC) has increased over recent decades. While significant progress has been achieved in immunotherapy, the five-year survival rate is still unsatisfactory because of the low response rate and acquired resistance in a few patients, which reflects the complexity of the immune microenvironment in HCC. In this study, TCGA-LIHC, ICGC-LIRI-JP, and GEO data sets were used to verify the role of MSTO1 in the pathogenesis and progression of HCC. We then identified spatial distribution and cellular source of MSTO1 expression using single-cell RNA-sequencing and spatial transcriptomics. We investigated possible downstream mechanism of MSTO1 with virtual knockdown, DepMap, and scRNA-seq analysis. We evaluated the importance of MSTO1 for clinical treatment from the perspective of immune infiltration, cell-cell communication, immunotherapy databases, and orthotopic HCC model treated by AAV8-shMsto1. MSTO1 was upregulated in HCC and correlated with clinical features, including poor overall survival and advanced tumor stage. Functionally, MSTO1 promoted colony formation, migration, invasion, and in vivo progression of HCC. Mechanistically, HSP90AB1 was a potential downstream effector of MSTO1, related to MYC signaling pathway. Additional pathway analysis of the trajectories and metabolites revealed a correlation between the MSTO1⁺ malignant cells with MYC signaling, metabolic pathway, as well as an immunosuppressive microenvironment. MSTO1 knockdown and anti-PD-1 therapy might play a synergistic role in the treatment of HCC. Overall, MSTO1 plays an important role during the development of HCC, and it was also associated with survival or response to immunotherapy. The progression of HCC may be associated with HSP90AB1 and MYC, and targeting MSTO1 may effectively enhance the efficacy of anti-PD-1 therapy.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"188 ","pages":"117358"},"PeriodicalIF":5.6,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897253","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":"Targeted drug delivery of rosuvastatin via nanoemulgel: A step towards more effective rheumatoid arthritis therapy.","authors":"Vrushali Pathade, Shweta Nene, Shreya Ratnam, Kamatham Pushpa Tryphena, Etikala Amulya, Ganesh Vambhurkar, Saurabh Srivastava","doi":"10.1016/j.intimp.2026.117351","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117351","url":null,"abstract":"<p><p>The intent of the current study was the repurposing of rosuvastatin (RSV), an anti-hyperlipidemic drug, for the management of rheumatoid arthritis (RA). Transdermal delivery of RSV, a repurposed drug, loaded in nanoemulgel (NEG) improves the permeation of the drug through the skin and reaches the desired site of action. This thereby enhances the concentration of the drug at the site of action, reducing the side effects associated with other routes of delivery, further showing anti-inflammatory potential in the management of RA. Nanoemulsion (NE) was prepared by the spontaneous emulsification method. The globule size and polydispersity index of the developed NE were evaluated by Malvern ZetaSizer. Furthermore, RSV-NEG has been developed and characterized. In vivo efficacy of RSV-NEG was evaluated in complete Freund's adjuvant-induced RA in rats. Pro-inflammatory cytokine concentrations in rat serum were quantified by enzyme-linked immunosorbent assay. The globule size and polydispersity index of 0.4% w/w RSV NE were found to be 8.96 ± 0.19 nm and < 0.3, respectively. The developed NEG showed pseudoplastic shear thinning behavior and an average drug content of 97.54 ± 0.36%. The RSV demonstrated 28-fold higher permeation from RSV-NEG compared to free RSV gel. The animals treated with RSV-NEG exhibited anti-inflammatory potential along with significantly reduced (****p < 0.0001) paw thickness and arthritis scores compared to the negative control group. The promising findings with permeability after topical application and anti-inflammatory potential emphasize the ability of RSV-NEG to manage RA effectively.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"188 ","pages":"117351"},"PeriodicalIF":5.6,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897280","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":"Vitamin D receptor regulates macrophage polarization and cuproptosis via transcriptional activation of ATP7B to mitigate intrauterine adhesion fibrosis.","authors":"Min Yong, Xixi Wu, Jianguo Hu","doi":"10.1016/j.intimp.2026.117332","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117332","url":null,"abstract":"<p><strong>Background: </strong>Intrauterine adhesion (IUA) significantly contributes to female infertility, primarily characterized by abnormal fibrotic remodeling of the endometrium. The intricate interplay among various cellular components within the endometrial microenvironment plays a pivotal role in IUA pathophysiology. Among these implicated factors, the vitamin D receptor (VDR) has emerged as a potential regulator of fibrotic processes; however, its specific role and underlying mechanisms in IUA remain inadequately understood. This study aimed to investigate the role of VDR in IUA pathogenesis and its impact on endometrial macrophage behavior.</p><p><strong>Methods: </strong>To investigate VDR's role in IUA, we conducted a comprehensive analysis of clinical endometrial samples from patients diagnosed with IUA. Complementary to this, we performed in vitro experiments using bone marrow-derived macrophages (BMDMs) obtained from both wild-type (WT) and VDR conditionnal knockout (VDR-cKO) mice. Furthermore, in vivo studies were carried out using an IUA mouse model alongside VDR-cKO mice to assess the physiological relevance of our findings.</p><p><strong>Results: </strong>Our investigation revealed a marked reduction in VDR expression within endometrial macrophages from IUA patients. In vitro assessments indicated that VDR deficiency led to enhanced pro-inflammatory M1 polarization, evidenced by increased level of iNOS and decreased CD206 in BMDMs. Mechanistically, VDR conditional knockout was found to induce cuproptosis, characterized by downregulation of ATP7B and upregulation of DLAT. Additionally, we demonstrated that VDR transcriptionally activates ATP7B expression, with luciferase reporter assays confirming VDR's direct binding to the ATP7B promoter. In vivo experiments further established that macrophage-specific VDR knockout intensified endometrial fibrosis, heightened M1 polarization, and increased cuproptosis in the IUA mouse model, while administration of a VDR agonist effectively reversed these phenotypic alterations.</p><p><strong>Conclusion: </strong>Our findings reveal a novel mechanistic pathway by which macrophage-specific VDR deficiency exacerbates IUA pathogenesis through dysregulation of the ATP7B-cuproptosis axis and promotion of profibrotic M1-like macrophage polarization. These insights suggest that VDR agonism may represent a promising therapeutic approach for the prevention and treatment of IUA, warranting further investigation into its clinical applicability.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"188 ","pages":"117332"},"PeriodicalIF":5.6,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897341","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":"Quercetin attenuates emamectin benzoate-induced myocardial PANoptosis in chickens: Critical role of the MAPK/NF-κB signaling pathway and mitochondrial dynamics.","authors":"Yong Liu, Bai He, Li Li, Chunhua Wang, Liping Zhang, Qingchun Mu, De Cai","doi":"10.1016/j.intimp.2026.117349","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117349","url":null,"abstract":"<p><p>Emamectin benzoate (EMB) is a highly effective and widely detected environmental insecticide whose potential to induce severe cardiotoxicity and localized myocardial inflammation has raised substantial biomedical concerns. Quercetin (Que), a ubiquitous plant-derived natural antioxidant, has shown promise in mitigating exogenous chemical-induced toxicities, yet its precise immunopharmacological mechanism against EMB-induced cardiotoxicity remains to be fully elucidated. This study investigated the protective effects and mechanisms of Que. against EMB-induced cardiotoxicity by integrating network toxicology, transcriptomics, and in vivo/in vitro experimental validation. Multi-omics analysis identified MAPK8, MAPK3, and CASP3 as key responsive targets conserved across species. Functional enrichment revealed that these targets are predominantly involved in the MAPK/NF-κB signaling pathway and mitochondrial organization. Molecular docking and targeted intervention experiments confirmed that Que. potentially targets and binds to JNK (encoded by MAPK8), thereby blocking the EMB-activated signaling axis. This molecular interaction effectively restored mitochondrial dynamics and prevented mitochondrial DNA leakage into the cytoplasm, ultimately alleviating myocardial PANoptosis. Collectively, our findings demonstrate that Que. serves as a natural antagonist against chemical-induced cardiotoxicity by modulating the MAPK/NF-κB axis, offering a promising therapeutic strategy for mitigating pesticide-related immunotoxicological risks.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"188 ","pages":"117349"},"PeriodicalIF":5.6,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897272","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":"Kaempferol for the treatment of asthma: A review of pre-clinical evidence on therapeutic potential and mechanism.","authors":"Yu Zhao Lee, Fui-Ling Voon, Hong Yee Chung, Jaimah Shakwat, Chau Ling Tham, Yu-Cheng Ho, Ming Tatt Lee","doi":"10.1016/j.intimp.2026.117364","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117364","url":null,"abstract":"<p><p>Asthma remains a significant global health burden characterised by high clinical heterogeneity and immunological complexity. Despite currently available therapies, limitations like steroid insensitivity and adverse side effects persist. Furthermore, recent biologics' high costs and accessibility remain a constraint. This emphasised the need for innovative alternative treatments. Kaempferol, a naturally occurring flavanol found in various fruits, vegetables, and medicinal plants, has gained considerable attention for its multifaceted pharmacological properties. This review critically assesses existing preclinical evidence regarding the therapeutic potential and molecular mechanisms of kaempferol in experimental asthma models. Preclinical in vivo and in vitro studies consistently demonstrate that kaempferol targets three critical dimensions of asthma pathogenesis: airway inflammation, hyperresponsiveness, and airway remodelling. Mechanistically, it suppresses the infiltration of inflammatory cells and reduces the secretion of pro-inflammatory cytokines, chemokines, and IgE. These effects are achieved by modulating key signalling pathways, including NF-κB, MAPKs, JAK/STAT, Nrf2, and NOX4-mediated autophagy. Furthermore, kaempferol alleviates smooth muscle hypercontractility and suppresses airway remodelling by mitigating subepithelial fibrosis, mucus hypersecretion, and epithelial-to-mesenchymal transition. Its translational strengths include potential steroid-sparing effects. Despite this, its clinical application is hindered by poor oral bioavailability and a lack of direct human trials. Rigorous clinical validation and advanced targeted delivery systems are required to establish kaempferol as a viable therapeutic agent for asthma management.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"188 ","pages":"117364"},"PeriodicalIF":5.6,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897282","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":"Comment on \"Hyperglycemia-triggered STAT3 activation drives thromboinflammation via NETs formation to promote hemorrhagic transformation after stroke\".","authors":"Yuan Yang","doi":"10.1016/j.intimp.2026.117356","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117356","url":null,"abstract":"<p><p>This correspondence provides a critical perspective on the recent study by Zhao et al. defining the hyperglycemia-STAT3-neutrophil extracellular trap-thromboinflammation axis in post-ischemic stroke hemorrhagic transformation. Beyond three core unresolved scientific gaps concerning cell-type specificity, tissue plasminogen activator-associated pathological context, and glycemic model heterogeneity, we extend the discussion to supplementary translational constraints, the upstream regulatory role of mitochondrial oxidative stress, and implications for clinical trial design. These viewpoints aim to further enhance the translational potential of this promising therapeutic target.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"188 ","pages":"117356"},"PeriodicalIF":5.6,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891589","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":"7,8-Dihydroxyflavone alleviates chronic prostatitis/chronic pelvic pain syndrome via modulation of the TrkB/AKT/ERK/SIRT3 signaling axis.","authors":"Peiqi Zhao, Wenhui Li, Yuyao Song, Bin Shen, Yi He, Jing Jin, Zhi He, Jinlai Gao","doi":"10.1016/j.intimp.2026.117333","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117333","url":null,"abstract":"<p><p>Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urological condition marked by ongoing oxidative stress and persistent inflammation, which complicates clinical management. This study examined the therapeutic effects and underlying mechanisms of 7,8-Dihydroxyflavone (7,8-DHF) in an experimental autoimmune prostatitis (EAP) mouse model, induced via subcutaneous immunization with prostate antigen in Complete Freund's Adjuvant. Mice were administered daily intraperitoneal injections of 7,8-DHF (5 mg/kg) and subsequently underwent a series of evaluations: prostate index measurement, abdominal tactile allodynia assessment using Von Frey filaments, cystometric analysis for urinary function, histological examinations with HE and Masson staining, quantitative PCR for pro-inflammatory cytokines, biochemical assays for oxidative stress markers (MDA, SOD, CAT, total antioxidant capacity), and Western blot analysis to assess activation of the TrkB/AKT/ERK/SIRT3 signaling pathway. 7,8-DHF treatment significantly decreased the prostate index, alleviated pelvic tactile allodynia, and improved bladder function in EAP mice. Histopathological analysis showed notable reductions in inflammatory cell infiltration and collagen deposition, along with decreased expression of pro-inflammatory cytokines (IL-6, IL-17α, MCP-1, IL-1β). Mechanistically, 7,8-DHF enhanced antioxidant capacity by increasing SOD/CAT activities and decreasing MDA levels, which correlated with TrkB phosphorylation, subsequent AKT/ERK pathway activation, upregulated SIRT3 expression, and MnSOD deacetylation. In vitro experiments with RWPE-1 cells demonstrated that 7,8-DHF mitigates LPS-induced oxidative stress and inflammation through mechanisms dependent on SIRT3. Collectively, these findings elucidated that 7,8-DHF could ameliorate CP/CPPS by activating the TrkB/AKT/ERK/SIRT3 signaling pathway to suppress oxidative stress and inflammatory reactions, highlighting its potential value as a novel therapeutic candidate for the clinical management of CP/CPPS.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"188 ","pages":"117333"},"PeriodicalIF":5.6,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891634","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 interrelated NLRP3 and NF-κβ signaling pathways to develop enhanced tolerogenic dendritic cells: Promising prospect for autoimmune disorders.","authors":"Shiva Alipour, Amirhossein Mardi, Dariush Shanehbandi, Leili Aghebati-Maleki, Tohid Kazemi","doi":"10.1016/j.intimp.2026.117354","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117354","url":null,"abstract":"<p><p>Proper immune response needs a regulated interaction between adaptive and innate immunity and dendritic cells (DCs) as professional antigen presenting cells coordinate their interaction. In order to maintain the balance between tolerance and initiation of immune response, these DCs should be activated in a regulated manner which is managed by diverse signaling pathways including nuclear factor kappa light chain enhancer of activated B cells (NF-κβ) and NLR family pyrin domain containing 3 (NLRP3). According to the vital role of DCs in immunity, it is a promising strategy to induce tolerogenic DCs (TolDCs) to suppress autologous T cell responses in patients with autoimmune disorders and targeting inflammatory signaling pathways is a potent strategy for induction of mentioned TolDCs. NF-κβ and NLRP3 signaling pathways play significant role in maturation, antigen presentation, and inflammatory function of DCs and finally affect their immune response which subsequently contributes to differentiation of T cells. According to the stated vital role of signaling pathways in DCs and their involvement in progression of autoimmune disorders, in this study we will review NF-κβ and NLRP3 signaling pathways and their contribution to DCs' immunogenicity and functionality and it will be discussed that how these signaling pathways are strictly regulated. Furthermore, this review sheds light on therapeutic role of NF-κβ and NLRP3 targeting for induction of potent TolDCs for the benefit of patients with diverse autoimmune disorders. Finally, due to the well-known role of NF-κβ as primary needed signal for assembly and full function of NLRP3 inflammasome we will mention the cross-talk between NF-κβ and NLRP3 pathways and highlight their interrelated targeting as a mechanistically rational approach that warrants future experimental investigation to evaluate effects of their simultaneous modulation for induction of favorable TolDC vaccines with both NF-κβ and NLRP3 being suppressed that not only disrupts the immunogenic function of DCs by inhibition of NF-κβ, but also prevents full activation of NLRP3 inflammasome.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"188 ","pages":"117354"},"PeriodicalIF":5.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887474","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":"The active ingredient madecassoside in Huyan no. 1 formula ameliorates D-gal-induced renal aging through the AMPK/MAPK/AP-1 signaling pathway.","authors":"Liyan Huang, Siyao Yu, Yining He, Yunyu Fang, Weiyi Yan, Kaizhi Wen, Xiaofan Yin, Chao Han, Xiaolin Zhu, Weiming He","doi":"10.1016/j.intimp.2026.117339","DOIUrl":"https://doi.org/10.1016/j.intimp.2026.117339","url":null,"abstract":"<p><strong>Background: </strong>Renal aging accelerates overall organismal aging. The traditional Chinese medicine formula Huyan I (HY-1) has been shown to slow the decline in kidney function, but its pharmacological mechanism is unclear. This study focuses on its active component, madecassoside (MA), aiming to elucidate how it delays renal aging.</p><p><strong>Methods: </strong>HY-1 was evaluated in a D-galactose-induced mouse model using renal functional, histopathological, inflammatory, and molecular assessments. Serum-absorbed constituents were characterized by UHPLC-MS/MS and analyzed using network pharmacology, molecular docking, MM/GBSA binding free-energy calculations, and molecular dynamics simulations. The anti-senescent effects of madecassoside (MA) were validated in vivo and in D-galactose-treated HK-2 cells. Transcriptomic sequencing and pharmacological pathway modulation were used to investigate the involvement and hierarchical relationship of the AMPK and MAPK/AP-1 signaling axes.</p><p><strong>Results: </strong>Both HY-1 and MA ameliorated renal pathological injury, improved the expression levels of aging-related proteins (p53, p21, p16), promoted AMPK phosphorylation, and reduced senescence-associated secretory phenotype (SASP) factors (IL-1β, IL-6, TNF-α) in mouse serum, thereby slowing overall aging. MA also reduced intracellular peroxide accumulation in HK-2 cells, restored mitochondrial membrane potential, and improved mitochondrial function. Transcriptomic analysis revealed that MA may exert anti-aging effects by suppressing the MAPK signaling pathway (inhibiting phosphorylation of p38, ERK, JNK) and reducing nuclear phosphorylation of c-Fos and c-Jun, affecting AP-1 transcription factor formation. When AMPK phosphorylation was inhibited, MA's anti-aging effect was abrogated, and MAPK pathway activation was enhanced.</p><p><strong>Conclusion: </strong>As the one of the principal active ingredients of HY-1, MA delays renal aging by promoting AMPK phosphorylation to maintain mitochondrial function and reduce peroxide accumulation, while inhibiting the MAPK signaling pathway to decrease AP-1 transcription factor synthesis.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"188 ","pages":"117339"},"PeriodicalIF":5.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887442","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}