Abstract
The medicinal herbal plant has been commonly used for prevention and intervention of disease and health promotions worldwide. Brazilein is a bioactive compound extracted from Caesalpinia sappan Linn. Several studies have showed that brazilein exhibited the immune suppressive effect and anti-oxidative function. However, the molecular targets of brazilein for inflammation prevention have remained elusive. Here, we investigated the mechanism underlying the inhibitory effect of brazilein on LPS-induced inflammatory response in Raw264.7 macrophage cells. We demonstrated that brazilein decreased the expression of IRAK4 protein led to the suppression of MAPK signaling and IKKβ, and subsequent inactivation of NF-κB and COX2 thus promoting the expression of the downstream target pro-inflammatory cytokines such as IL-1β, MCP-1, MIP-2, and IL-6 in LPS-induced Raw264.7 macrophage cells. Moreover, we observed that brazilein reduced the production of nitrite compared to the control in LPS-induced Raw264.7. Thus, we suggest that brazilein might be a useful bioactive compound for the prevention of IRAK-NF-κB pathway associated chronic diseases.
Highlights
The immune system is required for host defense and recognizes a variety of pathogen-associated molecular patterns (PAMPs) of invading microbial pathogens
We examined the inflammation-associated signaling which is influenced by brazilein in LPS-induced Raw264.7 macrophage cells
To evaluate the effect of brazilein on inflammation, we analyzed the expression of inflammatory genes or the level of nitric oxide (NO) by western blotting and cytokine assay
Summary
The immune system is required for host defense and recognizes a variety of pathogen-associated molecular patterns (PAMPs) of invading microbial pathogens. MyD88 activates the IL-1 receptor-associated kinase-4 (IRAK4) and tumor necrosis factor receptor-activated factor 6 (TRAF6) [10] These adaptor proteins lead to activation of transforming growth factor-beta-activated kinase 1 (TAK1) [11], which activate the downstream IκB kinase-α (IKKα) and IKKβ and mitogen-activated protein (MAP) 3-kinase pathways (extracellular signal-regulated protein kinase (ERK), c-Jun terminal kinase (JNK), and p38 MAPK) [12]. Transcriptional activation of interferon-regulatory factor 3 (IRF3) by these kinases regulates the expression of interferon-β (IFN-β) [17] The activation of these signaling pathways causes an excessive innate immune response, which can lead to chronic inflammatory diseases, such as cerebral ischemic injury [18], rheumatoid arthritis [19], and atherosclerosis [20]. We examined the inflammation-associated signaling which is influenced by brazilein in LPS-induced Raw264.7 macrophage cells
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