Synthesis and biological evaluation of curcumin derivatives containing NSAIDs for their anti-inflammatory activity.

Oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) was frequently associated with serious adverse effects. Inspired by curcumin-a naturally traditional Chinese medicine, a series of curcumin derivatives containing NSAIDs, used for transdermal application, were synthesized and screened for their anti-inflammatory activities in vitro and in vivo. Compared with curcumin and parent NSAID (salicylic acid and salsalate), topical application of A11 and B13 onto mouse ear edema, prior to TPA treatment markedly suppressed the expression of IL-1β, IL-6 and TNF-α, respectively. Mechanistically, A11 and B13 blocked the phosphorylation of IκBα and suppressed the activation of p65 and IκBα. It was found that A11 and B13 may be potent anti-inflammatory agents for the treatment of inflammatory diseases.