TY - JOUR T1 - 5,6,7-trimethoxyflavone suppresses pro-inflammatory mediators in lipopolysaccharide-induced RAW 264.7 macrophages and protects mice from lethal endotoxin shock. AU - Rim,Hong-Kun, AU - Yun,Chang Hyeon, AU - Shin,Ji-Sun, AU - Cho,Young-Wuk, AU - Jang,Dae Sik, AU - Ryu,Jong Hoon, AU - Park,Haeil, AU - Lee,Kyung-Tae, Y1 - 2013/10/24/ PY - 2013/07/09/received PY - 2013/10/14/revised PY - 2013/10/16/accepted PY - 2013/10/29/entrez PY - 2013/10/29/pubmed PY - 2014/8/16/medline KW - 5,6,7-Trimethoxyflavone KW - Cyclooxygenase-2 KW - Inducible nitric oxide synthase KW - Inflammation KW - Nuclear factor-kappa B KW - Sepsis SP - 847 EP - 55 JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JO - Food Chem Toxicol VL - 62 N2 - 5,6,7-Trimethoxyflavone (TMF), methylations of the hydroxyl groups of oroxylin A or baicalein, was found to significantly inhibit the productions of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. However, no report has been issued on the anti-inflammatory potential of TMF and the underlying molecular mechanism. In the present study, we investigated the anti-inflammatory effects of TMF in LPS-induced RAW 264.7 macrophages and LPS-induced septic shock in mice. TMF dose-dependently inhibits iNOS and COX-2 at the protein, mRNA, and promoter binding levels and that these inhibitions cause attendant decreases in the productions of NO and PGE2. TMF inhibits the productions and mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 induced by LPS. Furthermore, TMF suppress the transcriptional activity of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1), and nuclear translocations of NF-κB, AP-1, and signal transducer and activator of transcription 1/3 (STAT1/3). Pretreatment with TMF increase the survival rate of mice with LPS-induced endotoxemia and reduced the serum levels of cytokines. Taken together, these findings suggest that TMF down-regulates the expressions of the pro-inflammatory iNOS, COX-2, TNF-α, IL-1β, and IL-6 genes in macrophages by interfering with the activation of NF-κB, AP-1, and STAT1/3. SN - 1873-6351 UR - https://www.unboundmedicine.com/medline/citation/24161485/567_trimethoxyflavone_suppresses_pro_inflammatory_mediators_in_lipopolysaccharide_induced_RAW_264_7_macrophages_and_protects_mice_from_lethal_endotoxin_shock_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-6915(13)00700-X DB - PRIME DP - Unbound Medicine ER -