Find in Library

A series of 1,7-diphenyl-1,4-heptadien-3-ones with various substituents (HO-, CH₃O-, CH₃-, Cl-) on the phenyl rings were synthesized and evaluated for anti-neuroinflammatory effects in LPS-stimulated BV2 microglia. The pharmacological results showed that the target compounds bearing methoxy groups greatly inhibited LPS-induced NO release, and that the active compounds <b>CU-19</b> and <b>CU-21</b> reduced the level of NO, TNF-<i>α</i>, IL-6 and PGE-2, downregulated the expression of COX-2 and iNOS in LPS-stimulated BV2 cells. A study of the mechanism of action revealed that <b>CU-19</b> and <b>CU-21</b> inhibited the nuclear translocation of NF-<i>κ</i>B and phosphorylation of MAPKs (ERK, JNK, and p38). A preliminary pharmacokinetic study in rats revealed that the pharmacokinetic properties of <b>CU-19</b> and <b>CU-21</b> were dramatically ameliorated in comparison with the pharmacokinetic properties of curcumin.