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.
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.
Chao
Louis Kuoping
LK
Department of Cosmeceutics, China Medical University, Taichung, Taiwan.
Liao
Pei-Chun
PC
Ho
Chen-Lung
CL
Wang
Eugene I-Chen
EI
Chuang
Chao-Chin
CC
Chiu
Huan-Wen
HW
Hung
Lang-Bang
LB
Hua
Kuo-Feng
KF
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
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