Protective effects of (4-(1,2,4-oxadiazol-5-yl)phenyl)-2-aminoacetamide derivatives to adjuvant-induced arthritis rats by regulating the NF-κB signaling pathway.

A series of (4-(1,2,4-oxadiazol-5-yl) phenyl)-2-aminoacetamide derivatives showed good anti-neuroinflammation in our previous study. Some studies have proven that the anti-inflammatory compounds effective for some specific diseases could also be used to treat other inflammatory diseases. In this study, the effects of these compounds on arthritis were further analyzed. First, in-vitro anti-inflammatory activity assessment indicated that these compounds have good anti-inflammatory activity. Among them, compound f15 showed the most prominent performance, it could significantly inhibit the production of relevant inflammatory factors in lipopolysaccharide (LPS)-induced RAW264.7 cells, with IC50 values of 1.55 ± 0.33, 3.83 ± 0.19, and 7.03 ± 0.24 μM against NO, IL-1β, and TNF-α production, respectively. Preliminary mechanism studies indicated that f15 blocked the excitation of nuclear factor κB (NF-кB) signaling pathway in a concentration-dependent manner. Furthermore, in-vivo experiment showed that f15 reduced secondary foot swelling and arthritic index in adjuvant-induced arthritis (AIA) rats and inhibited the production of TNF-α and IL-1β in serum. Histopathological analysis revealed that f15 alleviated inflammatory cell infiltration and synovial hyperplasia in rats with AIA. Thus, compound f15 could be considered to have the potential to be developed as a treatment for arthritis.