RESUMEN
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 antiinflammatory activities, are limited. In the present study, the trienone 1,7bis(4hydroxy3methoxyphenyl)1,4,6heptatrien3one (HMPH) was structurally modified from curcumin using a novel and concise method. HMPH was shown to exhibit potential antiinflammatory effects on lipopolysaccharide (LPS)activated RAW264.7 macrophages. Furthermore, LPSinduced nitric oxide secretion in RAW264.7 cells was markedly and dosedependently 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 cyclooxygenase2 expression, as well as proinflammatory cytokine secretion. To elucidate the molecular mechanism underlying the antiinflammatory effects of HMPH, the effects of this compound on nuclear factorκB (NFκB) translocation were assessed. HMPH significantly inhibited the translocation of p65 NFκB into the nucleus to a greater extent than curcumin, thus indicating that HMPH has more potent antiinflammatory 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 antiinflammatory effects of HMPH may be through upstream inhibition of the inflammatory pathway. In conclusion, HMPH may be considered a promising compound for reducing inflammation via targeting p65 NFκB translocation and interfering with MD2 binding.