title: Curcumin and its major metabolites inhibit the inflammatory response induced by lipopolysaccharide: translocation of nuclear factor-κB as potential target.
abstract: The aim of the present study was to investigate and compare the anti‑inflammatory activities of curcumin and its three metabolites, tetrahydrocurcumin, hexahydrocurcumin and octahydrocurcumin in lipopolysaccharide (LPS)‑stimulated RAW 264.7 macrophage cells. The results demonstrated that overproduction of nitric oxide (NO) was potently inhibited following treatment with curcumin and its three metabolites. In addition, curcumin and tetrahydrocurcumin significantly inhibited the release of prominent cytokines, including tumor necrosis factor‑α (TNF‑α) and interleukin‑6 (IL‑6); however, hexahydrocurcumin and octahydrocurcumin did not significantly alter cytokine release. Furthermore, the present study investigated the effect of curcumin and its metabolites on the expression of inducible NO synthase (iNOS), cyclooxygenase‑2 (COX‑2) and activated‑nuclear factor kappa B (NF‑κB); the results showed that curcumin and its three metabolites significantly inhibited LPS‑mediated upregulation of iNOS and COX‑2 as well as NF‑κB activation. However, curcumin exerted a more potent effect on LPS‑stimulated RAW 264.7 cells compared to that of its three metabolites, of which tetrahydrocurcuim was found to be the most pharmacologically active. In conclusion, the results of the present study demonstrated that curcumin and its major metabolites inhibited the LPS‑induced inflammatory response via the mechanism of inhibiting NF‑κB translocation to the nucleus.
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Clinical Laboratory, Yantai Psychological Rehabilitation Hospital, Yantai, Shandong 265200, P.R. China.
authors.forename: Yudian
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China.
authors.forename: Daquan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Fu
authors.affiliation: Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D059748:Proteolysis; D051381:Rats
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; C569902:hexahydrocurcumin; C096277:tetrahydrocurcumin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D003474:Curcumin