Brazilein Suppresses Inflammation through Inactivation of IRAK4-NF-κB Pathway in LPS-Induced Raw264.7 Macrophage Cells

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.

K313, a novel benzoxazole derivative, exhibits anti‐inflammatory properties via inhibiting GSK3β activity in LPS‐induced RAW264.7 macrophages

“…The GSK-3β inhibitor LiCl effectively inhibited inflammatory cytokines by the increasing GSK-3β (Ser9) phosphorylation and GSK-3β inactivation. 32,34 Compared to LiCl treatment, K313 better inhibited NO, IL-6, and TNF-α secretion. Furthermore, K313 and LiCl had a synergistic effect on inhibiting NO, IL-6, and TNF-α secretion ( Figure 6A-C).…”

“…LPS‐induction increased the constitutive activity of GSK‐3β to induce NO, TNF‐α, and IL‐6 secretion in RAW264.7 macrophages, but K313 had anti‐inflammatory effects by increasing the phosphorylated GSK‐3β (Ser9) levels to decrease GSK‐3β activation (Figure B). The GSK‐3β inhibitor LiCl effectively inhibited inflammatory cytokines by the increasing GSK‐3β (Ser9) phosphorylation and GSK‐3β inactivation . Compared to LiCl treatment, K313 better inhibited NO, IL‐6, and TNF‐α secretion.…”

“…The NF-κB signaling pathway is a well-known classical signaling pathway that produces various inflammatory cytokines in LPS-induced RAW264.7 macrophages. 32,33 Thus, we hypothesized that K313 might regulate the NF-κB signaling pathway to inhibit inflammatory cytokines. The highest level of phospho-NF-κB p65 protein expression was detected at 30 min ( Figure 4A), and K313 had no influence on phospho-NF-κB p65 protein levels in LPS-induced RAW264.7 macrophages ( Figure 4B).…”

Anti-Inflammatory Potential of Rape Flower in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages

“…It is produced from the conversion of arachidonic acid by the inducible cyclooxygenase isoform, COX-2, which is induced by cytokines and other activators 15 . Therefore, we next examined the effects of RFE on PGE 2 production in LPS-stimulated RAW 264.7 macrophages.…”

Tanshinone IIA inhibits lipopolysaccharide‑induced inflammatory responses through the TLR4/TAK1/NF‑κB signaling pathway in vascular smooth muscle cells

“…It then upregulates the expression of cytokines, including McP-1, IL-6, TNF-α, and NO (47). Several studies have indicated that NF-κB may serve an important role in LPS-induced inflammation in macrophages and VSMcs (48,49). As a downstream molecule of TAK1, a reduction in NF-κB may contribute to the anti-inflammatory mechanism of Tan IIA.…”