Immunopharmacology and Immunotoxicology最新文献

{"title":"Silver nanoparticle-conjugated pyrimidine-based BN6 methanimine derivative improves DSS-induced inflammatory bowel disease in zebrafish.","authors":"Karthikeyan Ramamurthy, Magesh Santhanakrishnan, Jagan Kannan, Coimbatore Ravindran Cibikeerthivas, Vellapandian Chitra, Rajakrishnan Rajagopal, Ahmed Alfarhan, Bader O Almutairi, Ki Choon Choi, Kathiravan Muthu Kumaradoss, Senthilkumar Palaniappan, Jesu Arockiaraj","doi":"10.1080/08923973.2026.2671717","DOIUrl":"10.1080/08923973.2026.2671717","url":null,"abstract":"<p><strong>Background: </strong>Treatment for inflammatory bowel diseases (IBD) include immunosuppressant and steroids for managing the inflammation. Also, these treatments have many negative complications, limited efficacy, and development of drug resistance.</p><p><strong>Objective: </strong>To synthesize the (Z)-N-(4-(2-chlorophenyl)-6-(4-nitrophenyl)pyrimidin-2-yl)-1-(furan-2-yl)methanimine (named BN6) derivative and examines its anti-inflammatory, antioxidant, and drug-delivery effectiveness of silver nanoparticle (AgNPs) nanoconjugates against dextran sulfate sodium (DSS) induced IBD in an <i>in-vivo</i> zebrafish model.</p><p><strong>Methods: </strong>The synthesis and evaluation of AgNPs-BN6 derivatives conducted through <i>in vitro</i> studies. The drug release profile was studied at pH 7.0, simulating intestinal conditions, and the entrapment efficiency was evaluated across a range of concentrations, from 10 to 160 μM. Inflammatory marker levels (<i>tnf-α</i>, <i>il-1β</i>, <i>cox-2</i>, and <i>il-10</i>), biochemical changes (SOD, CAT, GSH, and LDH), macrophage localization, oxidative stress and cellular damages were measured in a following AgNPs-BN6 treatment at concentrations of 40 μM, 80 μM, and BN6 (100 μM).</p><p><strong>Results: </strong>AgNPs-BN6 conjugate drug release at 80 μM peaked at over 80% within 5 h under intestinal pH, with a slight decrease noted at 10 h. The highest entrapment efficiency, 82.30 ± 0.25, was observed at 80 μM, showcasing a dose-dependent increase until that concentration. In the model group, inflammatory markers <i>tnf-α</i>, <i>il-1β</i>, and <i>cox-2</i> were particularly elevated, signaling inflammation, whereas AgNPs-BN6 treatment at 80 μM effectively lowered these markers, reinstating balance with inflammatory genes. Additionally, AgNPs-BN6 treatment reduces oxidative stress markers, demonstrating its antioxidant properties.</p><p><strong>Conclusion: </strong>AgNPs-BN6 derivatives, especially at 80 μM, possess substantial anti-inflammatory and antioxidant properties, emphasizing their potential as effective therapeutic agents for inflammatory disease.</p><p><strong>Clinical trail: </strong>Not Applicable.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"539-551"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874199","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":"Rituximab beyond oncology: targeting B-cell-mediated immunomodulatory therapy in neurodegenerative and neuropsychiatric disorders.","authors":"Trina Saha, Tanya Vats, Sidharth Mehan","doi":"10.1080/08923973.2026.2671714","DOIUrl":"10.1080/08923973.2026.2671714","url":null,"abstract":"<p><strong>Objective: </strong>Neurological and neuropsychiatric disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), autoimmune encephalitis (AE), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), are associated with neuroinflammation, oxidative stress, protein aggregation, and blood-brain barrier disruption. This review aimed to evaluate the immunomodulatory and neuroprotective potential of rituximab in these disorders and summarize its mechanisms of action, therapeutic efficacy, and clinical limitations.</p><p><strong>Materials and methods: </strong>A comprehensive review of preclinical and clinical studies investigating rituximab in neurodegenerative and neuropsychiatric disorders was conducted. Relevant evidence regarding B cell-mediated pathology, rituximab's mechanisms of action, therapeutic outcomes, adverse effects, and emerging clinical applications was analyzed and synthesized.</p><p><strong>Results: </strong>Rituximab, a chimeric monoclonal antibody targeting CD20-positive B cells, exerts therapeutic effects through complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and apoptosis induction. In MS, rituximab reduces pro-inflammatory cytokines, immune cell activation, and demyelination, thereby slowing disease progression. Preclinical findings in AD and PD suggest that rituximab mitigates B cell-mediated neuroinflammation and oxidative stress, contributing to neuroprotection. Furthermore, rituximab has demonstrated clinical efficacy in AE, NMOSD, and MOGAD by depleting pathogenic B cells and reducing relapse frequency. However, treatment-associated complications such as hypogammaglobulinemia, infections, and infusion-related reactions remain significant concerns requiring careful monitoring and dose optimization.</p><p><strong>Conclusions: </strong>Rituximab represents a promising immunomodulatory therapy for several neurological and neuropsychiatric disorders driven by B cell-mediated pathology. Its ability to modulate neuroinflammation and immune dysfunction highlights its therapeutic potential in neuroimmunology. Future studies should focus on improving central nervous system penetration, identifying predictive biomarkers of response, and exploring combination therapies to enhance efficacy and safety outcomes.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"583-618"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874242","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":"Pharmacovigilance analysis of vonoprazan: a disproportionality analysis based on the FDA adverse event reporting system database.","authors":"Boyi Liu, Wenchao Zhang, Ao Han, Danna Chen","doi":"10.1080/08923973.2026.2673951","DOIUrl":"10.1080/08923973.2026.2673951","url":null,"abstract":"<p><strong>Objective: </strong>Vonoprazan is a novel potassium-competitive acid blocker whose expanding clinical application necessitates comprehensive evaluation of its real-world safety profile.</p><p><strong>Methods: </strong>Utilizing the FAERS database, this study collected adverse event (AE) data associated with vonoprazan therapy from the first quarter of 2013 to the second quarter of 2025. Disproportionality analysis was performed using both the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) methods. Furthermore, a Weibull distribution model was employed to characterize the temporal risk patterns of the identified adverse events.</p><p><strong>Results: </strong>A total of 1315 reports of adverse events (AEs) associated with vonoprazan were identified in this study. Analysis revealed several potential safety signals, including: gastric cancer (ROR = 9.26, 95%CI: 5.48-15.65; IC = 3.21, IC025 = 1.83), dysgeusia (ROR = 2.31, 95%CI: 1.24-4.29; IC = 1.2, IC025 = 0.17), and esophageal candidiasis (ROR = 36.36, 95%CI: 18.16-72.82; IC = 5.18, IC025 = 1.92).</p><p><strong>Conclusion: </strong>Although signal detection analysis based on the FAERS database cannot establish causality, our study suggests that vonoprazan treatment may significantly increase the risks of nausea, hypertension, and gastric cancer, highlighting the need for enhanced monitoring in clinical practice. Future research should validate these signals through prospective trials and mechanistic studies to optimize the risk-benefit profile of vonoprazan therapy.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"701-711"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147963593","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":"Mono(2-ethylhexyl) phthalate modulates bone marrow-derived APCs and exacerbates allergic lung inflammation <i>via</i> PPARγ-dependent pro-inflammatory signaling.","authors":"Hsin-Han Tseng, Yu-Wei Chang, Ting-I Lin, Hui-Chun Yang, Shin-Ting Wu, Jau-Ling Suen","doi":"10.1080/08923973.2026.2671722","DOIUrl":"10.1080/08923973.2026.2671722","url":null,"abstract":"<p><strong>Background: </strong>Mono(2-ethylhexyl) phthalate (MEHP), the active metabolite of the plasticizer di-(2-ethylhexyl) phthalate (DEHP), has been implicated in the rising prevalence of allergic diseases. However, its immunotoxic mechanisms remain incompletely understood. In this study, we investigated the immunomodulatory effects of MEHP under tolerable daily intake (TDI)-equivalent exposure conditions using both <i>in vivo</i> and <i>in vitro</i> approaches.</p><p><strong>Methods: </strong>An ovalbumin (OVA)-induced allergic lung inflammation model was used in C57BL/6 mice chronically exposed to DEHP or MEHP. Cytokine profiles in bronchoalveolar lavage fluid (BALF) and anti-OVA IgE levels in serum were assessed using ELISA. <i>In vitro</i>, granulocyte-macrophage colony-stimulating factor <b>(</b>GM-CSF)-differentiated bone marrow-derived antigen-presenting cells (BM-APCs) were treated with MEHP, with or without PPARγ antagonist or agonist. Surface marker expression and cytokine production were evaluated by flow cytometry and ELISA, and IκBα phosphorylation was assessed by immunoblotting.</p><p><strong>Results: </strong>TDI-equivalent DEHP or MEHP exposure exacerbated allergic lung inflammation, with elevated Th2/Th1 cytokines in bronchoalveolar lavage fluid and serum anti-OVA IgE levels. <i>In vitro</i>, MEHP-treated BM-APCs showed increased IL-6 and IL-12 production, along with reduced IL-10, MHC class II, and CD86 expression. These effects were partially reversed by a modulator of peroxisome proliferator-activated receptor gamma (PPARγ) antagonist and recapitulated by a PPARγ agonist. MEHP also induced IκBα phosphorylation, suggesting activation of NF-κB independently of PPARγ.</p><p><strong>Conclusion: </strong>Mechanistically, our findings indicate that MEHP modulates APC cytokine profiles and surface phenotype through both PPARγ-dependent and -independent pathways. MEHP exposure aggravated lung inflammation and increased IgE levels at TDI-equivalent doses, supporting its pathogenic potential under physiologically relevant conditions.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"619-629"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874206","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":"From the lab to the feed: science communication through an immunological lens in the social media era.","authors":"Mohamed Abd El-Salam","doi":"10.1080/08923973.2026.2685542","DOIUrl":"10.1080/08923973.2026.2685542","url":null,"abstract":"","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"525-527"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301200","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":"Omarigliptin attenuates thioacetamide-induced hepatic fibrosis in rats by activating SIRT1/Nrf2 and inhibiting NF-κB/TGF-β1 pathways.","authors":"Abdulaziz Alarifi, Marwa Qadri, Daniyah A Almarghalani, Ali Alquraini, Faisal K Alkholifi, Fadhel A Alomar, Moudi M Alasmari, Aya A Shokry, Passant E Moustafa, Hany M Fayed, Marwa E Shabana","doi":"10.1080/08923973.2026.2673944","DOIUrl":"10.1080/08923973.2026.2673944","url":null,"abstract":"<p><strong>Background: </strong>Hepatic fibrogenesis, a reversible but serious condition characterized by excessive extracellular matrix deposition, can progress to cirrhosis. This study examined the multi-mechanistic protective effects of the dipeptidyl peptidase-4 inhibitor Omarigliptin (OMR) against thioacetamide (TAA)-induced hepatic fibrogenesis.</p><p><strong>Methods: </strong>Rats were grouped into control, TAA (100 mg/kg, IP, twice weekly, 6 weeks), and TAA plus OMR (2.5 or 5 mg/kg/day, orally, last 4 weeks).</p><p><strong>Results: </strong>TAA induced substantial liver damage, evidenced by elevated serum alanine aminotransferase, aspartate aminotransferase, triglycerides, and cholesterol, alongside decreased albumin and total protein. TAA further triggered oxidative stress, depleting glutathione and superoxide dismutase, raising malondialdehyde, and suppressing the SIRT1/Nrf2 axis. Additionally, TAA elevated pro-inflammatory (TNF-α, IL-1β, NF-κB p65) and pro-fibrotic (TGF-β1, α-SMA) markers, paralleled by histopathological injury and increased fibrosis scores. OMR treatment, particularly at 5 mg/kg, attenuated TAA-induced liver dysfunction, oxidative stress, inflammation, and fibrosis.</p><p><strong>Conclusion: </strong>OMR exerts hepatoprotective and anti-fibrotic effects against TAA-induced injury by activating SIRT1/Nrf2 and suppressing NF-κB and TGF-β1 signaling. These multi-mechanistic actions support its repurposing for fibrotic liver diseases.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"630-641"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972163","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":"Nano-enabled strategies for enhancing cancer immunotherapy: challenges, progress and perspective.","authors":"Hazem Mathkour","doi":"10.1080/08923973.2026.2673541","DOIUrl":"10.1080/08923973.2026.2673541","url":null,"abstract":"<p><strong>Objective: </strong>To review the role of nanotechnology in enhancing cancer immunotherapy, particularly immune checkpoint blockade (ICB), adoptive cell therapy (ACT), and cancer vaccines. It addresses key challenges in solid tumors, including poor drug delivery, immunosuppressive tumor microenvironment (TME), immune resistance, and treatment-related toxicity.</p><p><strong>Methods: </strong>A narrative review of recent preclinical and clinical studies was conducted to evaluate how nanoplatforms improve targeted delivery, modulate the TME, enhance immune activation, and support immunotherapeutic efficacy. Challenges related to biosafety, biodistribution, scalability, and clinical translation were also discussed.</p><p><strong>Results: </strong>Current findings demonstrate that nanotechnology-based platforms can significantly improve cancer immunotherapy outcomes. Nanomedicines enhance ICB by increasing intratumoral drug accumulation and reversing immune suppression within the TME. In ACT, nanoplatforms improve T cell persistence, function, and tumor infiltration. Nanoformulations also strengthen cancer vaccines through more efficient antigen delivery and enhanced antigen presentation.</p><p><strong>Conclusion: </strong>Preclinical and early clinical studies suggest that nano-immunotherapies can overcome important biological barriers and enhance antitumor immune responses while reducing systemic toxicity.</p><p><strong>Discussion: </strong>Overall, nano-immunotherapy represents a promising strategy for improving the efficacy of cancer immunotherapy, particularly in solid tumors. Despite progress, several challenges remain, including long-term safety concerns, variability in nanoparticle design, manufacturing scalability, regulatory issues, and limited clinical data. Further researches are needed to optimize delivery systems, ensure safety, and facilitate successful clinical translation toward more effective and personalized cancer treatments.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"675-700"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211143","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":"Statement of Retraction: Amygdalin Induces Apoptosis in Human Cervical Cancer Cell Line HeLa Cells.","authors":"","doi":"10.1080/08923973.2026.2675070","DOIUrl":"10.1080/08923973.2026.2675070","url":null,"abstract":"","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"738"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149700","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 comparative analysis of MSCs and their exosomes in osteoarthritis therapy: complementary roles and clinical translation.","authors":"Nada Khairi Younis, Hayder Naji Sameer, Hasanain Amer Naji, M M Rekha, Laxmidhar Maharana, Anima Nanda, Vipasha Sharma, Ashish Singh Chauhan, Rasim M Salih, Mohaned Adil, Farzaneh Yazdi","doi":"10.1080/08923973.2026.2673950","DOIUrl":"10.1080/08923973.2026.2673950","url":null,"abstract":"<p><strong>Objective: </strong>There is presently no cure for osteoarthritis (OA). Despite the promise of mesenchymal stem cell (MSC) transplantation, issues such as low cell survival and engraftment have shifted research toward MSC-derived exosomes (MSC-EXOs). Because they mirror the immunomodulatory and tissue-regenerative actions of MSCs without the safety and logistical issues of cell-based therapies, MSC-EXOs constitute an emerging class of medicines. This paper compares and contrasts MSCs and MSC-EXOs for OA treatment.</p><p><strong>Materials and methods: </strong>A literature search was conducted in PubMed, Google Scholar, Web of Science, Scopus, and ClinicalTrials.gov from 2000 to 2025 using keywords related to MSCs, exosomes, and osteoarthritis.</p><p><strong>Results: </strong>Using data from clinical trials that consistently show symptomatic relief but inconsistent evidence of structural cartilage regeneration, we describe MSC characteristics and assess their therapeutic benefits and limitations. The review further examines pathways by which MSC-EXOs mediate reparative effects in injured joint tissue, noting that while preclinical results are encouraging, clinical confirmation is lacking. MSC-EXOs have less developed evidence bases and greater regulatory uncertainty than MSCs, but offer advantages in safety, targeting, and scalability. Standardizing EXO manufacturing and purification, identifying optimal dosing schedules, establishing long-term safety profiles, and engineering EXOs for improved targeting and efficacy remain key translational challenges.</p><p><strong>Conclusions: </strong>MSC-EXO-based treatment demonstrates potential as a regenerative approach for OA.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"642-674"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971877","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":"Targeting alpha 7 nicotinic acetylcholine receptors by galantamine alleviates doxorubicin-induced cardiotoxicity <i>via</i> modulation of PI3K/AKT, Bax/Bcl-2, and NF-κB/TNF-α pathways.","authors":"Yasmeen M Abozaid, Marwa M Khalaf, Maha M Abdel-Fattah, Mohamed A Khattab, Basim Anwar Shehata Messiha","doi":"10.1080/08923973.2026.2673955","DOIUrl":"10.1080/08923973.2026.2673955","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin is a potent anthracycline employed in the management of several malignant conditions. While it serves as an effective anticancer agent, its therapeutic application is constrained by dose-dependent cardiotoxicity. Galantamine is a reversible competitive antagonist of cholinesterase utilized in the management of Alzheimer's disease.<b>Aim of the work</b>This work sought to ascertain the cardioprotective benefits of GALA versus cardiotoxicity triggered by DOX and elucidate the fundamental molecular pathways.</p><p><strong>Materials and methods: </strong>Rats were randomized to four groups, as follows: control, GALA (5 mg/kg, P.O.), DOX single dose (20 mg/kg, I.P), and DOX + GALA.</p><p><strong>Results: </strong>Unlike the DOX group, GALA pretreatment mitigated cardiotoxicity, as revealed by a notable drop in serum CK-MB and CTnI, along with marked improvement in the histopathological features of heart tissues. GALA also diminished oxidative damage, as recognized by reduced MDA and elevated GSH and SOD. Moreover, GALA pretreatment reduced DOX-induced inflammation, as revealed by a decline in NF-κB, along with TNF-α and IL-6. Furthermore, GALA pretreatment mitigated DOX's apoptotic effects, as revealed by reduced Bax and caspase-3, alongside an elevation in Bcl-2 and its upstream signaling pathway PI3K/AKT.</p><p><strong>Conclusion: </strong>These findings indicated that GALA's protective impact versus DOX-induced cardiotoxicity is attributed to its capability to modulate PI3K/AKT, Bax/Bcl-2, and NF-κB/TNF-α pathways.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"572-582"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972153","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}