Unveiling the anti-inflammatory effects and mechanisms of LM49 in a carrageenan-induced acute inflammation model  

多酚化合物LM49对角叉菜胶诱导足肿胀小鼠的抗炎作用及机制研究

作　　者：Fan Yang Rui Li Wenting Liu Jian Sun Chengxiao Zhao Xiue Feng Qingshan Li 杨帆;李蕊;刘雯婷;孙舰;赵承孝;冯秀娥;李青山(山西医科大学药学院/教育部慢性肾病医药基础研究创新中心,山西太原030001;山西中医药大学基于炎性反应的重大疾病创新药物山西省重点实验室,山西太原030619)

机构地区：[1]School of Pharmaceutical Science,Medicinal Basic Research Innovation Center of Chronic Kidney Disease,Ministry of Education,Shanxi Medical University,Taiyuan 030001,Shanxi,China [2]Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on Chronic Inflammation,Shanxi University of Chinese Medicine,Taiyuan 030619,Shanxi,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2025年第1期41-54,共14页中国药学(英文版)

基　　金：The National Natural Science Foundation of China(Grant No.82003770);the National Science and Technology Major Project of China(Grant No.2018ZX09711001-001-017);the Key Research and Development Plan of Shanxi Province(Grant No.202102130501005)。

摘　　要：This study aimed to investigate the anti-inflammatory properties and underlying molecular mechanisms of 2,4',5'-trihydroxyl-5,2'-dibromo diphenylmethanone(LM49)using a carrageenan-induced paw edema model in mice,which serves as a well-established model for acute inflammation.Mice were randomly assigned into six groups,and acute inflammation was induced by injecting 1%carrageenan solution into the paw.To elucidate the anti-inflammatory effects and mechanisms of LM49,a comprehensive approach was employed,including pathology,transcriptomics,flow cytometry,RT-qPCR,Western blotting analysis,and molecular docking analysis.The results demonstrated that LM49 exerted a significant protective effect by reducing paw edema and lowering serum levels of pro-inflammatory cytokines IL-1βand TNF-a,while concurrently elevating anti-inflammatory cytokine IL-10 levels.Transcriptomic analysis identified 453 differentially expressed genes in the LM49-treated group.KEGG and GO enrichment analyses indicated that LM49 suppressed the NF-kB signaling pathway and modulated several other immuneinflammatory pathways.Molecular docking studies identified eight key targets of LM49 within the NF-kB signaling pathway.Furthermore,Western blotting analysis confirmed that LM49 inhibited the phosphorylation of p65 and IB-αand downregulated the expression of MYD88 and TLR4 in mouse paw tissues.These findings provided a foundational understanding of the anti-inflammatory effects and molecular mechanisms of LM49,paving the way for further in-depth studies in this field.本研究旨在评价2,4',5'-三羟基-5,2'-二溴二苯甲酮(LM49)对角叉菜胶诱导足肿胀模型小鼠的抗炎作用及潜在机制。小鼠随机分为6组,采用1%角叉菜胶溶液构建小鼠足肿胀模型。运用病理学、转录组学、流式细胞术、RT-qPCR、Western blot、分子对接等方法,研究LM49在角叉菜胶诱导的足肿胀模型中的抗炎作用及其机制。结果显示LM49可明显减轻小鼠足部水肿形成,降低血清促炎因子IL-1β和TNF-α水平,提高血清抑炎因子IL-10水平。转录组学分析显示,LM49组中有453个差异表达基因,KEGG和GO分析表明,LM49抑制NF-κB信号通路,并影响其他一些免疫炎症信号通路。分子对接揭示了LM49在NF-κB信号通路中的8个关键靶点。Westernblot结果证实,LM49能抑制小鼠足组织中p65和IκB-α的磷酸化,以及MYD88和TLR4的表达。本研究结果为进一步研究LM49的抗炎作用及分子机制提供了重要依据。

关 键 词：ANTI-INFLAMMATION TRANSCRIPTOMIC Molecular docking CARRAGEENAN 2 4' 5'-Trihydroxyl-5 2'-dibromo diphenylmethanone 

分 类 号：R961.1[医药卫生—药理学]