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

doi:10.5246/jcps.2025.01.004

Abstract

Abstract:

This study aimed to investigate the anti-inflammatory properties and underlying molecular mechanisms of 2,4ʹ,5ʹ-trihydroxyl-5,2ʹ-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-1β and TNF-α, 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-κB signaling pathway and modulated several other immune-inflammatory pathways. Molecular docking studies identified eight key targets of LM49 within the NF-κB signaling pathway. Furthermore, Western blotting analysis confirmed that LM49 inhibited the phosphorylation of p65 and IκB-α and 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.

Key words: Anti-inflammation, Transcriptomic, Molecular docking, Carrageenan, 2,4?,5?-Trihydroxyl-5,2?-dibromo diphenylmethanone

Supporting:

Fan Yang, Rui Li, Wenting Liu, Jian Sun, Chengxiao Zhao, Xiue Feng, Qingshan Li. Unveiling the anti-inflammatory effects and mechanisms of LM49 in a carrageenan-induced acute inflammation model[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(1): 41-54.

Figures/Tables 7

Table 1. Primers used for the RT-qPCR study.

Table 2. LM49 and some protein macromolecular docking box parameters.

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