TY - JOUR AB - 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 structurally modified from curcumin using a novel and concise method. HMPH was shown to exhibit potential anti‑inflammatory effects on lipopolysaccharide (LPS)‑activated RAW264.7 macrophages. Furthermore, LPS‑induced nitric oxide secretion 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 cyclooxygenase‑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 inflammatory pathway. In conclusion, HMPH may be considered a promising compound for reducing inflammation via targeting p65 NF‑κB translocation and interfering with MD2 binding. AD - School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80161, Thailand Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand Department of Microbiology, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand Department of Pre‑Clinic, Faculty of Science and Technology, Prince of Songkla University, Pattani Campus, Pattani 94000, Thailand AU - Jansakun,Chutima AU - Chulrik,Wanatsanan AU - Chaichompoo,Waraluck AU - Yotmanee,Pathumwadee AU - Lehboon,Kanokporn AU - Chunglok,Wilanee AU - Sattayakhom,Apsorn AU - Hiransai,Poonsit AU - Kamdee,Kornyok AU - Utaipan,Tanyarath AU - Suksamrarn,Apichart AU - Chunglok,Warangkana DA - 2021/03/01 DO - 10.3892/mmr.2021.11848 IS - 3 JO - Mol Med Rep KW - trienone curcumin NF‑κB MD2 PY - 2021 SN - 1791-2997 1791-3004 SP - 209 ST - 1,7‑Bis(4‑hydroxy‑3‑methoxyphenyl)‑1,4,6‑heptatrien‑3‑one alleviates lipopolysaccharide‑induced inflammation by targeting NF‑κB translocation in murine macrophages and it interacts with MD2 in silico T2 - Molecular Medicine Reports TI - 1,7‑Bis(4‑hydroxy‑3‑methoxyphenyl)‑1,4,6‑heptatrien‑3‑one alleviates lipopolysaccharide‑induced inflammation by targeting NF‑κB translocation in murine macrophages and it interacts with MD2 in silico UR - https://doi.org/10.3892/mmr.2021.11848 VL - 23 ER -