Synthesis and Anti-Neuroinflammatory Activity of 1,7-diphenyl-1,4-heptadien-3-ones in LPS-Stimulated BV2 Microglia Via Inhibiting NF-κB/MAPK Signaling Pathways |
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| Authors: | Xuan Zhao Jiqing Fang Yu Jia Zi Wu Meihui Zhang Mingyu Xia Jinhua Dong |
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| Affiliation: | 1.Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang City 110016, China; (X.Z.); (Y.J.); (M.Z.);2.School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang City 110016, China; (J.F.); (Z.W.) |
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| Abstract: | 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 CU-19 and CU-21 reduced the level of NO, TNF-α, 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 CU-19 and CU-21 inhibited the nuclear translocation of NF-κB and phosphorylation of MAPKs (ERK, JNK, and p38). A preliminary pharmacokinetic study in rats revealed that the pharmacokinetic properties of CU-19 and CU-21 were dramatically ameliorated in comparison with the pharmacokinetic properties of curcumin. |
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| Keywords: | curcumin 1 7-diphenyl-1 4-heptadien-3-one neuroinflammation anti-inflammation BV2 cell synthesis |
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