ASPP 092, a phenolic diarylheptanoid from Curcuma comosa suppresses experimentally-induced inflammatory ear edema in mice

Abstract

Curcuma comosa Roxb., family Zingiberaceae, exhibits diverse biological activities. This study was aimed to investigate the anti-inflammatory potential of a major phenolic diarylheptanoid isolated from C. comosa, ASPP 092 [(3S)-1-(3,4-dihydroxy-phenyl)-7-phenyl-(6E)-6-hepten-3-ol] in an experimentally-induced inflammatory ear edema model in mice. Ear edema in the mice was induced by the topical application of irritant, ethyl phenylpropiolate (EPP). The topical application of ASPP 092 at the edema site was directed immediately after the EPP application. The edematous responses were assessed at different time points by measuring the thickness of each ear before and after the EPP application followed by histopathology analysis. The expressions of major inflammatory cytokines were analyzed by real-time RT-PCR followed by the immunohistochemistry analysis of cyclooxygenase (COX-2). The topical application of ASPP 092 effectively suppressed the EPP-induced edematous formation in the ear of mice. Histopathological analysis showed substantial improvements in epidermal hyperplasia and inflammatory cell infiltration. ASPP 092 treatment also modulated the expressions of inflammatory cytokines including Tumor Necrosis Factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1β (IL-1β), and Matrix metalloproteinase-13 (MMP-13). The expressions of cyclooxygenases (COX) including COX-1 and COX-2 were significantly reduced by ASPP 092 treatment. For the first time, our results suggest the efficacy of ASPP 092 to suppress experimentally-induced inflammation in a preclinical model in mice; however, a more detailed evaluation of its mechanism of action is necessary before evaluating its efficacy and safety in randomized trials.