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Front Pharmacol


4–Carboxymethylascochlorin Inhibits Expression Levels of on Inflammation-Related Cytokines and Matrix Metalloproteinase-9 Through NF-κB/MAPK/TLR4 Signaling Pathway in LPS-Activated RAW264.7 Cells.


Park J Y, Ha S-H, Abekura F, Lim H, Magae J, Ha K-T, Chung T-W, Chang Y-C, Lee Y-C, Chung E Y, Ku J, Kim C-H
Front Pharmacol. 2019; 10:304.
PMID: 31001118.


Toll-like receptor 4 (TLR4) and matrix metalloproteinase-9 (MMP-9) are known to play important roles in inflammatory diseases such as arteriosclerosis and plaque instability. The purpose of this study was to perform the effect of 4–carboxymethylascochlorin (AS-6) on MMP-9 expression in lipopolysaccharide (LPS)-induced murine macrophages and signaling pathway involved in its anti-inflammatory effect. Effect of AS-6 on MAPK/NF-κB/TLR4 signaling pathway in LPS-activated murine macrophages was examined using ELISA, Western blotting, reverse transcription polymerase chain reaction (RT-PCR) and fluorescence immunoassay. MMP-9 enzyme activity was examined by gelatin zymography. AS-6 significantly suppressed MMP-9 and MAPK/NF-κB expression levels in LPS-stimulated murine macrophages. Expression levels of inducible nitric oxide synthase (iNOS), COX2, MMP-9, JNK, ERK, p38 phosphorylation, and NF-κB stimulated by LPS were also decreased by AS-6. Moreover, AS-6 suppressed TLR4 expression and dysregulated LPS-induced activators of transcription signaling pathway. The results of this study showed that AS-6 can inhibit LPS-stimulated inflammatory response by suppressing TLR4/MAPK/NF-κB signals, suggesting that AS-6 can be used to induce the stability of atherosclerotic plaque and prevent inflammatory diseases in an model.