title: Luteolin and chicoric acid synergistically inhibited inflammatory responses via inactivation of PI3K-Akt pathway and impairment of NF-κB translocation in LPS stimulated RAW 264.7 cells.
abstract: Synergistic anti-inflammatory effects of luteolin and chicoric acid, two abundant constituents of the common dandelion (Taraxacum officinale Weber), were investigated in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Co-treatment with luteolin and chicoric acid synergistically reduced cellular concentrations of nitric oxide (NO) and prostaglandin E2 (PGE2) and also inhibited expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, co-treatment reduced the levels of proinflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. Both luteolin and chicoric acid suppressed oxidative stress, but they did not exhibit any synergistic activity. Luteolin and chicoric acid co-treatment inhibited phosphorylation of NF-κB and Akt, but had no effect on extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38. This anti-inflammatory signaling cascade coincides with that affected by luteolin treatment alone. These results suggest that luteolin plays a central role in ameliorating LPS-induced inflammatory cascades via inactivation of the NF-κB and Akt pathways, and that chicoric acid strengthens the anti-inflammatory activity of luteolin through NF-κB attenuation.
authors.affiliation: Department of Smart Foods and Drugs, Inje University, Gimhae, Republic of Korea.
authors.forename: Chung Mu
authors.initials: CM
authors.lastname: Park
authors.forename: Kyong-Suk
authors.initials: KS
authors.lastname: Jin
authors.forename: Yong-Woo
authors.initials: YW
authors.lastname: Lee
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Song
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002109:Caffeic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D015232:Dinoprostone / Q000096:biosynthesis; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D047311:Luteolin / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013386:Succinates / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D002109:Caffeic Acids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D021122:Protein Subunits; D013386:Succinates; D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D015232:Dinoprostone; D047311:Luteolin; C100435:chicoric acid