Abstract
AimsAtherosclerosis is the main cause of cardiovascular disease and is widely treated with statins. However, there are a few cases of intolerable adverse reactions by statins; thus, there is still a need for new drugs to prevent atherosclerosis. The inflammation associated with the activation of Toll-like receptor 4 (TLR4) and nuclear factor κB (NFκB) has been shown to be an important factor in the development of atherosclerosis. In the current study, we investigated the anti-inflammatory action of the fungal alkaloid fumigaclavine C (FC), its effects on the TLR4 and NFκB signaling pathway, and its potential relevance as an anti-atherosclerotic agent. Main methodsThe inhibitory effects of FC on tumor necrosis factor α (TNFα) production were determined by enzyme-linked immunosorbent assays (ELISA). The mRNA and protein expression of TLR4 and p65NFκB were detected by quantitative real-time polymerase chain reaction and western blot analysis, respectively. The effect of FC on NFκB was determined using the Dual-Luciferase reporter assay. Key findingsFC reduced TNFα production in LPS-stimulated human whole blood and RAW 264.7 macrophages via reduced IκBα phosphorylation associated with the decreased expression of p65NFκB. FC also suppressed LPS-induced TLR4 overexpression at the mRNA and protein level. SignificanceFC attenuated TNFα via the TLR4-NFκB signaling transduction pathway, suggesting that this alkaloid might serve as a promising molecule for anti-inflammatory treatment of atherosclerosis.
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