Biomolecules & Therapeutics最新文献

{"title":"Crebanine Protects HUVECs from LPS-Induced Inflammation and Oxidative Stress by Suppressing NF-κB Pathway.","authors":"Hao Chen, Liyuan Luo, Yunzhu Guo, Yong Liu, Weidan Luo","doi":"10.4062/biomolther.2025.215","DOIUrl":"10.4062/biomolther.2025.215","url":null,"abstract":"<p><p>Endothelial dysfunction induced by inflammation and oxidative stress represents a critical pathological mechanism in cardiovascular and cerebrovascular diseases, including sepsis and atherosclerosis. Although crebanine has been reported to possess anti-inflammatory and analgesic properties, its effects on inflammation and oxidative stress in endothelial cells remain unknown. In this study, we assessed cell viability, apoptosis, and migration using the Cell Counting Kit-8 (CCK-8), flow cytometry, and a wound healing assay, respectively. The levels of reactive oxygen species (ROS) and the expression of inflammatory and oxidative stress markers were determined by qRT-PCR, enzyme-linked immunosorbent assay (ELISA), and Western blotting analysis. Our results demonstrated that crebanine alleviated lipopolysaccharide (LPS)-induced apoptosis and dysfunction in human umbilical vein endothelial cells (HUVECs). Crebanine treatment inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), ROS, and malondialdehyde (MDA), while it enhanced the activity of the antioxidant enzyme superoxide dismutase (SOD). Mechanistically, crebanine suppressed LPS-induced activation of the NF-κB signaling pathway in HUVECs. Furthermore, the improvement effect of crebanine on the inflammation and dysfunction in LPS-treated HUVECs was reversed by diprovocim, an NF-κB activator. These findings suggest that crebanine ameliorates LPS-induced inflammation and oxidative stress in HUVECs by inhibiting the NF-κB signaling pathway, indicating its potential therapeutic value for treating vascular endothelial dysfunction-related diseases.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"423-433"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Adenosine Receptors in Sleep Deprivation-Induced Depression-Like Behaviors.","authors":"Nan Ju Lee, Yi-Sook Jung","doi":"10.4062/biomolther.2025.263","DOIUrl":"10.4062/biomolther.2025.263","url":null,"abstract":"<p><p>Sleep deprivation (SD) disrupts homeostatic regulation and increases vulnerability to stress and mood disorders. This study investigated the duration-dependent effects of SD and elucidated the distinct roles of adenosine A₁ receptors (A₁R) and A_2A receptors (A_2AR) in behavioral and molecular alterations induced by 24, 48, and 72 h of SD in mice. SD for 48 h and 72 h, but not 24 h, significantly increased immobility time in the tail suspension test (TST) and forced swim test (FST), accompanied by elevated plasma corticosterone (CORT) levels, indicating a duration-dependent stress response. Hippocampal A₁R mRNA expression was significantly reduced, whereas A_2AR mRNA expression was markedly increased at 48 h and 72 h of SD. Pharmacological blockade of either A₁R (DPCPX) or A_2AR (SCH 58261) significantly attenuated SD-induced depression-like behaviors and CORT elevation, whereas activation of A₁R with the agonist CPA exacerbated depression-like behavior at 24 h and 48 h of SD. These findings suggest that A_2AR upregulation may represent a pathological response to prolonged SD, whereas A₁R downregulation may reflect compensatory adaptation to sustained receptor activation. Taken together, our results demonstrate that A₁R and A_2AR play distinct roles in SD-induced depression-like behaviors.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"356-364"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Celafolin A-1 Ameliorates Subretinal Fibrosis via Inhibition of Crystallin Alpha B in a Laser-Induced Choroidal Neovascularization Mouse Model.","authors":"Eunhye Yu, Sun Mi Gu, Haechan Kim, Jun Gu Kim, Bang Yeon Hwang, Jung Kee Min, Jaesuk Yun","doi":"10.4062/biomolther.2025.103","DOIUrl":"10.4062/biomolther.2025.103","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is a leading cause of blindness in people over 65 years old. Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for neovascular AMD (nAMD); however, fibrosis remains an unmet medical need due to the lack of effective medications. This study evaluated eight natural products from <i>Celastrus orbiculatus</i>, which has been reported to have anti-inflammatory effects, for their effects on the fibrotic pathological process as well as choroidal neovascularization (CNV). We investigated the half-maximal inhibitory concentration (IC₅₀) values of these compounds on VEGF and alphasmooth muscle actin (α-SMA, a fibrosis marker) expression-induced by human acute monocytic cell (THP-1) conditioned media in retinal pigment epithelium cells (ARPE-19). Four compounds reduced both VEGF and α-SMA at 10 μM, with three-Celafolin A-1, COFH5645, and COFH543435-showing the highest potency. Intravitreal injections of the compound in a mouse model of CNV induced by laser photocoagulation confirmed its efficacy. Celafolin A-1 significantly reduced α-SMA and VEGF expression and decreased hyper-reflective lesions and CNV areas. Binding affinity measurements using biolayer interferometry identified an interaction between Celafolin A-1 and crystallin alpha B (Cryab), a protein involved in stress responses and fibrosis. Celafolin A-1 reduced the expression levels of Cryab as well as its phosphorylated form at Ser45, indicating that its mechanism involves the regulation of Cryab phosphorylation. Taken together, Celafolin A-1 exhibits dual inhibitory effects on VEGF and fibrosis, suggesting it as a candidate for the treatment of nAMD.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"434-447"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"γ-Oryzanol Ameliorates Endothelial Replicative Senescence via Downregulation of SGLT2 Expression to Attenuate NADPH-Driven Oxidative Stress.","authors":"Saugat Shiwakoti, Kushal Sharma, Dal-Seong Gong, Ju-Young Ko, In-Young Lee, Hyun-Jung Kim, Min-Ho Oak","doi":"10.4062/biomolther.2025.133","DOIUrl":"10.4062/biomolther.2025.133","url":null,"abstract":"<p><p>Replicative senescence in endothelial cells is characterized by an irreversible cell cycle arrest and impaired endothelial function, contributing to vascular aging and cardiovascular disease. Natural compounds are being actively studied for their potential to delay cellular senescence and protect vascular health. Among them, rice bran has demonstrated several vascular benefits that are mainly attributed to gamma-oryzanol (γ-Orz), a major bioactive component in rice bran. However, its role in regulating endothelial replicative senescence and the underlying molecular mechanisms remain unclear. This study aimed to explore the protective effects of rice bran extract (RBE) and γ-Orz on replicative senescence in porcine coronary artery endothelial cells (PCAECs). Replicative senescence was modeled in PCAECs by serial passaging from P1 to P3 with varying concentrations of RBE and γ-Orz. Senescence was evaluated by measuring senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, oxidative stress, and the expression of cell cycle regulatory proteins. RBE and γ-Orz significantly reduced SA-β-gal activity, improved proliferation, and decreased oxidative stress in P3 cells, along with downregulation of senescence-related proteins p53, p21, and p16. Additionally, γ-Orz suppressed sodium-glucose co-transporter 2 expression, reduced NADPH oxidase overexpression, and restored eNOS levels. These findings indicate that RBE and γ-Orz delay endothelial senescence by alleviating oxidative stress, highlighting their potential to reduce cardiovascular disease risk associated with endothelial senescence.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"401-412"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aβ₁₋₄₀ Enhances Platelet Sensitivity to Thrombin via NADPH Oxidase-ROS Signaling and Integrin α_IIbβ_₃ Engagement.","authors":"Been Kim, Bo Kyung Lee, Jung-Ae Kim, Yi-Sook Jung","doi":"10.4062/biomolther.2025.227","DOIUrl":"10.4062/biomolther.2025.227","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is increasingly recognized as a disorder with significant vascular involvement, with microvascular damage and thromboinflammation often preceding classical amyloid pathology by several years. Elevated levels of prothrombin and thrombin, along with aberrant platelet activation, have been reported in individuals with AD. We hypothesized that platelet hyperactivity in AD results from an exaggerated response to thrombin in the presence of elevated amyloid beta 1-40 (Aβ₁₋₄₀), a peptide that accumulates during the early stages of AD. Platelet activation in response to Aβ₁₋₄₀ and thrombin was assessed using aggregation assays with an aggregometer, adhesion measurements by confocal microscopy, and spreading via both confocal microscopy and scanning electron microscopy. Reactive oxygen species (ROS) production and integrin α_IIbβ₃ activation were quantified by flow cytometry. The roles of NADPH oxidase (NOX), ROS, and integrin signaling were examined using selective inhibitors. Aβ₁₋₄₀ significantly enhanced thrombin-induced platelet adhesion, aggregation, and spreading via NOX-derived ROS and integrin α_IIbβ₃ activation. Aβ₁₋₄₀ also promoted platelet binding to fibrinogen and cerebrovascular endothelial cells, accompanied by distinct morphological changes. Inhibition of NOX or integrin α_IIbβ₃ significantly reduced these effects. These findings identify a novel Aβ₁₋₄₀-NOX-ROS-integrin α_IIbβ₃ axis that drives platelet hyperactivation and cerebrovascular interactions in AD. Targeting this pathway with antithrombotic or antioxidative strategies may offer therapeutic potential in mitigating AD-associated vascular pathology.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"365-378"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring <i>LEPR</i>-Linked Metabolic Diversity through Gut Microbiome-Metabolome Network Analysis in Non-Obese Adults.","authors":"Kyeong-Seog Kim, Joo-Youn Cho, Ye Chan Park, Jang Hee Hong, Jin-Gyu Jung, Jung Sunwoo","doi":"10.4062/biomolther.2025.161","DOIUrl":"10.4062/biomolther.2025.161","url":null,"abstract":"<p><p>Genetic variation in the leptin receptor (<i>LEPR</i>) gene has been implicated in metabolic regulation, while the gut microbiome and circulating metabolites are increasingly recognized as mediators of host metabolic phenotype. However, the systems-level interactions among <i>LEPR</i> genotypes, gut microbial composition, and serum metabolomic profiles remain poorly understood, particularly in healthy individuals. We conducted a cross-sectional study involving 37 healthy Korean adults. Three <i>LEPR</i> single nucleotide polymorphisms (rs1137101, rs1173100, rs790419) were genotyped. Untargeted metabolomics of fasting serum was performed using gas chromatography-time-of-flight mass spectrometry, and gut microbiome composition was profiled by 16S rRNA gene sequencing. Statistical analysis included principal component analysis, Mann-Whitney U tests, and Spearman correlations. Network analysis integrating microbiome, metabolomic, and clinical phenotype data was conducted using Cytoscape. A total of 54 serum metabolites were identified. <i>LEPR</i> genotypes, particularly rs1137101 and rs1173100, were associated with differences in metabolites such as pimelic acid, malonic acid, and 2,4-dihydroxybutyric acid. Firmicutes negatively correlated with saturated fatty acids and organic acids, whereas Actinobacteria positively correlated with cholesterol and amino acids. Network analysis revealed indole-3-acetate and cholesterol as central nodes linking microbial taxa with body mass index and leptin levels. However, no direct molecular pathways connecting leptin or its receptor were identified. <i>LEPR</i> genetic variation is associated with distinct serum metabolomic patterns and microbiome-host networks in healthy adults. Although no direct leptin signaling links were found, network-level associations suggest indirect genetic influences on metabolic states through microbiome-metabolome interactions. These findings advance understanding of personalized metabolic regulation and gene-microbiome interplay.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"448-460"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quinoxaline Derivatives in Cancer Therapy: Insights into Mechanisms of Action and Therapeutic Applications.","authors":"Jinan Alhuwayshil, Nouf Alnajim, Sarah Bin Dulaym, Jehan Alamre, Arwa Alsubait, Afrah E Mohammed, Sahar S Alghamdi","doi":"10.4062/biomolther.2025.061","DOIUrl":"10.4062/biomolther.2025.061","url":null,"abstract":"<p><p>Cancer continues to be a leading cause of morbidity and mortality globally, which necessitates the development of more effective and less toxic therapies. Quinoxaline derivatives, a class of heterocyclic compounds with versatile chemical structures, have emerged as promising candidates for anticancer drug development. These derivatives exhibit a range of biological activities and have shown significant efficacy against various tumors. However, the therapeutic potential of quinoxaline derivatives, particularly in clinical applications, remains underexplored, highlighting the need for further research to optimize their use as anticancer agents. This systematic review aims to provide an updated analysis of quinoxaline derivatives' anticancer potential, focusing on their mechanisms of action and therapeutic applications in oncology. Following PRISMA guidelines, a thorough search was conducted in MEDLINE/PubMed and Science Direct for studies from 2020 to 2024. Relevant keywords were used to identify studies on quinoxaline derivatives and their anticancer properties, resulting in the selection of 77 studies based on pharmacological activity and mechanisms. The review included 77 studies exploring various anticancer activities of quinoxaline derivatives. Key findings indicate that these compounds effectively inhibit cancer cell growth through multiple mechanisms, including the inhibition of topoisomerases, kinases, and other critical proteins involved in cancer progression. Additionally, they demonstrate strong antiproliferative and pro-apoptotic effects across several cancer cell lines, highlighting their broad therapeutic potential. Quinoxaline derivatives represent a promising class of compounds in anticancer therapy due to their diverse biological activities and multiple molecular targets. The development of these derivatives as targeted therapies holds the potential for more effective cancer treatments.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"291-324"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phage Display Technology: Design, Library Construction, and Panning Strategies for Antibody Development.","authors":"Hobin Yang","doi":"10.4062/biomolther.2025.158","DOIUrl":"10.4062/biomolther.2025.158","url":null,"abstract":"<p><p>Phage display technology serves as a powerful <i>in vitro</i> platform for discovering antigen-specific antibodies, enabling the rapid identification and engineering of monoclonal antibodies for therapeutic applications. This review discusses key factors such as phagemid vector, antibody fragment formats, in-frame selection strategies, and effective library size in the context of maximizing functional diversity. Based on these factors, a detailed comparison of phage display antibody libraries is provided, including naïve, synthetic, and semi-synthetic formats, with emphasis on their distinctive features and design strategies. Furthermore, major panning strategies-solid-phase, liquid-phase, and cell-based panning-are compared, highlighting their respective strengths and limitations for isolating functional binders with regard to antigen presentation, epitope accessibility, and selection fidelity. Collectively, the refinement of library design and selection methodologies has led to the development of numerous approved antibodies, establishing phage display as a foundational technology in antibody drug discovery. Ultimately, this review aims to facilitate the effective application of phage display technology in developing antibody-based therapeutics.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"325-344"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploratory Proteomic Profiling Reveals Potential Mediators of 5-FU Response under p53 Deficiency in Colon Cancer Cells.","authors":"Seonyong Lee, Jiwon Lee, Ga Seul Lee, Jeong Hee Moon, Joohee Jung","doi":"10.4062/biomolther.2024.234","DOIUrl":"10.4062/biomolther.2024.234","url":null,"abstract":"<p><p>Mutations in p53 have been implicated in poor prognosis and reduced sensitivity to 5-fluorouracil (5-FU) treatment in colon cancer. While p53-dependent mechanisms have been widely studies, less is known about how p53 deficiency reshapes cellular signaling and contributes to 5-FU resistance. In this study, we aimed to profile proteomic alterations associated with p53 loss by comparing colon cancer cells with and without p53 expression. Differentially expressed proteins (DEPs) related to cell cycle regulation were of particular interest, as 5-FU treatment induced G1 phase arrest in HCT116 p53 wild-type (WT) cells, whereas p53 knockout (KO) cells predominantly showed S phase arrest. We identified several DEPs in p53 deficient cells following 5-FU treatment. Notably, F3 expression was increased, while aldehyde dehydrogenase family 1 member A4 (ALDH1A3), histone deacetylase 2 (HDAC2), and protein S100-A4 (S100A4) were decreased. The expression levels of these genes were associated with overall survival in patients with colon cancer. These findings highlight proteomic alterations linked to p53 deficiency and support a proposed model in which differential regulation of specific proteins may be associated with reduced sensitivity to 5-FU, providing a basis for future mechanistic and functional studies.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"391-400"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147301749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pluviatolide Attenuates Type I Hypersensitivity through Regulation of Mast Cell Activation.","authors":"Seon Young Kim, Jeong Won Park, Juhyun Shin, Ji-Ae Lee, Sun-Hee Leem, Min Geun Jo, Min Yeong Choi, Wahn Soo Choi, Keun Young Min, Geunwoong Noh, Sung-Jin Bae, Yung Hyun Choi, Hyuk Soon Kim","doi":"10.4062/biomolther.2025.164","DOIUrl":"10.4062/biomolther.2025.164","url":null,"abstract":"<p><p>This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrow-derived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptorindependent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 2","pages":"413-422"},"PeriodicalIF":4.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}