摘要
巨噬细胞介导的炎症反应和泡沫化是动脉粥样硬化(atherosclerosis,AS)的核心环节,但靶向调控CD40-CD40L通路的天然药物研究仍存在不足.研究旨在阐明corilagin通过这一通路抑制巨噬细胞活化的分子机制,为天然药物抗AS治疗提供新靶点.体外实验采用LPS诱导的RAW264.7巨噬细胞损伤模型,通过CCK-8、油红O染色及胆固醇检测发现,corilagin(IC50=41.25μmol/L)可显著抑制细胞增殖及泡沫化(p<0.05).进一步机制研究表明,corilagin下调CD40-CD40L-TRAF-1通路关键分子(mRNA及蛋白水平)及促炎因子(IL-6、IFN-γ),同时增加iNOS表达(p<0.05).通过联合CD40-CD40L抑制剂(DRI-C21045)验证,该通路被确认为corilagin作用的核心靶点.研究首次揭示corilagin通过调控CD40-CD40L-TRAF-1轴抑制巨噬细胞活化及脂质蓄积,为天然药物干预AS提供了新靶点和实验依据.
Although macrophage-mediated inflammatory responses and foam cell formation play pivotal roles in atherosclerosis(AS),research on natural compounds targeting the CD40-CD40L signaling pathway remains limited.This study aims to elucidate the molecular mechanism by which corilagin inhibits macrophage activation through this pathway,thereby providing novel therapeutic targets for natural product-based AS treatment.In vitro experiments utilizing an LPS-induced RAW264.7 macrophage injury model demonstrated that Corilagin(IC50=41.25μmol/L)significantly suppressed cell proliferation and foam cell formation(p<0.05),as determined by CCK-8 assay,Oil Red O staining,and cholesterol quantification.Mechanistic investigations revealed that Corilagin downregulated key components of the CD40-CD40L-TRAF-1 pathway(at both mRNA and protein levels)and proinflammatory cytokines(IL-6,IFN-γ),while upregulating iNOS expression(p<0.05).The essential role of this pathway was further confirmed through co-treatment with a specific CD40-CD40L inhibitor(DRI-C21045).This study provides the first evidence that Corilagin attenuates macrophage activation and lipid accumulation by modulating the CD40-CD40L-TRAF-1 axis,offering new insights into the potential application of natural products for AS intervention.
作者
张莉
高伟民
蔡静
王雨婷
倪若妍
喻卓
陈鹏
ZHANG Li;GAO Weimin;CAI Jing;WANG Yuting;NI Ruoyan;YU Zhuo;CHEN Peng(School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products,Kunming Medical University,Kunming 650500,Yunnan,China;College of Modern Biomedical Industry,Kunming Medical University,Kunming 650500,Yunnan,China;Department.of Cardiology,the First Affiliated Hospital of Kunming Medical University,Kunming 650032,Yunnan,China)
出处
《云南大学学报(自然科学版)》
北大核心
2025年第4期754-765,共12页
Journal of Yunnan University(Natural Sciences Edition)
基金
国家自然科学基金(82360088)
云南省科技厅–昆明医科大学联合专项重点项目(202201AY070001-001)
云南省教育厅科学研究基金(2024J0155).
