Synthesis and Anti-inflammatory Effects of Oxaprozin-Paeonol Ester

Oxaprozin is a common anti-inflammatory drug in the clinic. Oral medication of oxaprozin potentially induces the GI perforation, which is caused by the local irritation of its carboxylic acid group. Paeonol is an active ingredient of peony, and has anti-inflammatory and anti-oxidant effects. So oxaprozin-paeonol ester (OPE) was designed to avoid the GI complications and enhence corresponding anti-inflammatory. The topical anti-inflammatory effects of OPE was evaluated in a 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mouse ear edema model. The results showed that topical treatment of OPE could effectively improve the TPA-induced ear edema and its anti-inflammatory effect is 2 times higher than that of oxaprozin and 4 times than that of paeonol. Moreover, OPE treatment could effectively mitigate the expression of IL-1, IL-6, and TNF-, and its effect is better than that of oxaprozin or paeonol. Furthor study demonstrated that topical treatment of OPE could obviously down-regulate the activation of factor kappa-B (NF-B) by blocking IB kinase (IKK) activities. Accordingly, OPE might be used as a promising anti-inflammatory agent for inflammation-associated skin diseases.