Background: 3,4-dihydroxycinnamic acid and its derivatives exhibit numerous biologic activities. Such activities
have not previously been reported for 3,5-dihydroxycinnamic acid derivatives. In this study, ten derivatives of 3,5-
dihydroxycinnamic acid were synthesized and their anti-inflammatory activities were tested in 12-O-tetradecanoylphorbol
13-acetate-induced mouse ear edema. Molecular biological studies have shed lights on their anti-inflammatory mechanism.
Methods: Anti-inflammatory activities of ten new synthesized derivatives of 3,5-dihydroxycinnamic acid were tested in
12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema, and their anti-inflammatory mechanism was studied by
ELISA, real-time RT-PCR, MPO assay and AA-induced mouse ear edema.
Results: Compound 7 showed a pronounced anti-inflammatory effect and the inhibition rate was 65.6% at a dose of
1.6mg/ear. This compound acted by reducing mRNA and protein synthesis of tumor necrosis factor-α, interleukins 1β and
6, and also by decreasing the levels of activated neutrophil infiltrates. Furthermore, compound 7 significantly suppressed
arachidonic acid-induced edema as well. Cell-based assays showed that compound 7 inhibited the production of cyclooxygenase-
2-catalyzed prostaglandin E2 from lipopolysaccharide-treated RAW 264.7 cells, and also inhibited 5-lipoxygenase
production from A23187-treated RBL-1 cells, and consequently reduced leukotriene B4 production.
Conclusion: This investigation revealed that some of the derivatives of 3,5-dihydroxycinnamic acid exhibit a more pronounced
anti-inflammatory effect than 3,4-dihydroxycinnamic acid. Therefore, 3,5-dihydroxycinnamic acid derivatives,
especially compound 7, represent potential value for antiinflammatory drug development.