Brazilin selectively disrupts proximal IL-1 receptor signaling complex formation by targeting an IKK-upstream signaling components

Astragalin inhibits IL-1β-induced inflammatory mediators production in human osteoarthritis chondrocyte by inhibiting NF-κB and MAPK activation

“…Normally, NF-κB is present in cytoplasmic and bound to the repressor of NF-κB (IκBs). Once stimulated by IL-1β, IκB proteins are phosphorylated and degraded and NF-κB p65 translocates from the cytoplasm to the nucleus to regulate the production of inflammatory mediators [27][28][29]. In this study, we found that astragalin inhibited IL-1β-induced NF-κB activation in chondrocytes.…”

Post-translational control of NF-κB signaling by ubiquitination

“…PolyUb chains linked to TRAF6 interact with TAB 2 and activate TAB 2-associated TAK1, which activates the IKK complex by directly phosphorylating its activation loop. Alternatively, TRAF6 induces K63-linked poly-ubiquitination of IRAK1, which plays an essential role in the recruitment of IKK-c, and in activation of the IKK complex under particular conditions (Windheim et al 2008;Jeon et al 2014). In addition to TRAF6, Pellino protein families also possess a ring-like domain in the C-terminus that seems to function as an E3 Ub ligase and directly catalyzes polyubiquitination of IRAK1 in the IL-1R and TLR4 signaling pathways (Humphries and Moynagh 2015).…”

Brazilin plays an anti-inflammatory role with regulating Toll-like receptor 2 and TLR 2 downstream pathways in Staphylococcus aureus-induced mastitis in mice

“…Furthermore, many studies have shown that brazilin is involved in the regulation of either NF-κB or activator protein 1 (AP-1) activation [19,23]. It has been reported that the anti-inflammatory activity of brazilin involves the downstream pathway of TLR-mediated innate immune reactions [24]. Thus, the present study was performed to determine the effect of brazilin on the inflammatory response in the mouse model of S. aureus mastitis and to confirm the mechanism of action involved.…”