Abstract

Trienones are curcuminoid analogues and are minor constituents in the rhizomes of numerous Curcuma plant species. Studies investigating the biological activities of trienones, particularly their anti-inflammatory activities, are limited. In the present study, the trienone 1,7-bis(4-hydroxy-3- methoxyphenyl)-1,4,6-heptatrien-3-one (HMPH) was struc- turally modified from curcumin using a novel and concise method. HMPH was shown to exhibit potential anti-inflamma- tory effects on lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Furthermore, LPS-induced nitric oxide secre- tion in RAW264.7 cells was markedly and dose-dependently inhibited by HMPH; in addition, HMPH had a greater efficacy compared with curcumin. This inhibition was accompanied by the suppression of inducible nitric oxide synthase and cyclo- oxygenase-2 expression, as well as pro-inflammatory cytokine secretion. To elucidate the molecular mechanism underlying the anti-inflammatory effects of HMPH, the effects of this compound on nuclear factor-κB (NF-κB) translocation were assessed. HMPH significantly inhibited the translocation of p65 NF-κB into the nucleus to a greater extent than curcumin, thus indicating that HMPH has more potent anti-inflammatory activity than curcumin. In addition, an in silico modelling study revealed that HMPH possessed stronger binding energy to myeloid differentiation factor 2 (MD2) compared with that of curcumin, and indicated that the anti-inflammatory effects of HMPH may be through upstream inhibition of the inflam- matory pathway. In conclusion, HMPH may be considered a promising compound for reducing inflammation via targeting p65 NF-κB translocation and interfering with MD2 binding.