title: Anti-inflammatory bioactivities of honokiol through inhibition of protein kinase C, mitogen-activated protein kinase, and the NF-kappaB pathway to reduce LPS-induced TNFalpha and NO expression.
abstract: Much recent research has demonstrated that honokiol, a phenolic compound originally isolated from Magnolia officinalis, has potent anticancer activities; however, the detailed molecular mechanism of its anti-inflammatory activity has not yet been fully addressed. In this study we demonstrated that honokiol inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha secretion in macrophages, without affecting the activity of the tumor necrosis factor-alpha converting enzyme. At the same time, honokiol not only inhibited nitric oxide expression in LPS-stimulated murine macrophages but also inhibited the LPS-induced phosphorylation of ERK1/2, JNK1/2, and p38. By means of confocal microscope analysis we demonstrated that phosphorylation and membrane translocation of protein kinase C-alpha, as well as NF-kappaB activation, were inhibited by honokiol in LPS-stimulated macrophages. Furthermore, it was found that honokiol neither antagonizes the binding of LPS to cells nor alters the cell surface expression of toll-like receptor 4 and CD14. Our current results have exhaustively described the anti-inflammatory properties of honokiol, which could lead to the possibility of its future pharmaceutical application in the realm of immunomodulation.
authors.affiliation: Department of Cosmeceutics, China Medical University, Taichung, Taiwan.
authors.forename: Louis Kuoping
authors.initials: LK
authors.lastname: Chao
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Liao
authors.forename: Chen-Lung
authors.initials: CL
authors.lastname: Ho
authors.forename: Eugene I-Chen
authors.initials: EI
authors.lastname: Wang
authors.forename: Chao-Chin
authors.initials: CC
authors.lastname: Chuang
authors.forename: Huan-Wen
authors.initials: HW
authors.lastname: Chiu
authors.forename: Lang-Bang
authors.initials: LB
authors.lastname: Hung
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Hua
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000276:immunology / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000276:immunology / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D009569:Nitric Oxide / Q000276:immunology*; D011493:Protein Kinase C / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D017705:Lignans; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D009569:Nitric Oxide; D011493:Protein Kinase C; D014409:Tumor Necrosis Factor-alpha; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols