Anti-inflammatory effect of honokiol is mediated by PI3K/Akt pathway suppression
Aim: In this study, we investigated the regulatory effects of honokiol on various inflammatory events mediated by monocytes/macrophages (U937/RAW264.7 cells) and lymphocytes (splenic lymphocytes and CTLL-2 cells) and their putative action mechanism. Methods: In order to investigate the regulatory ef...
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Published in | Acta pharmacologica Sinica Vol. 29; no. 1; pp. 113 - 122 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
United States
Nature Publishing Group
01.01.2008
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Subjects | |
Online Access | Get full text |
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Summary: | Aim: In this study, we investigated the regulatory effects of honokiol on various inflammatory events mediated by monocytes/macrophages (U937/RAW264.7 cells) and lymphocytes (splenic lymphocytes and CTLL-2 cells) and their putative action mechanism. Methods: In order to investigate the regulatory effects, various cell lines and primary cells (U937, RAW264.7, CTLL-2 cells, and splenic lymphocytes) were employed and various inflammatory events, such as the production of inflammatory mediators, cell adhesion, cell proliferation, and the early signaling cascade, were chosen. Results: Honokiol strongly inhibited various inflammatory responses, such as: (i) the upregulation of nitric oxide (NO), pros- taglandin.E2 and TNF-α production and costimulatory molecule CD80 induced by lipopolysaccharide (LPS); (ii) the functional activation of β1-integrin (CD29) assessed by U937 cell-cell and cell-fibronectin adhesions; (iii) the enhancement of lymphocytes and CD8+CTLL-2 cell proliferation stimulated by LPS, phytohemaglutinin A (PHA), and concanavalin A or interleukin (IL)-2; and (iv) the transcriptional upregulation of inducible NO synthase, TNF-α, cyclooxygenase-2, IL- 12, and monocyte chemoattractant protein (MCP)- 1. These anti-inflammatory effects of honokiol seem to be mediated by interrupting the early activated intracellular signaling molecule phosphoinositide 3-kinase (PI3K)/Akt, but not Src, the extracellular signal-regulated kinase, and p38, according to pharmacological, biochemical, and functional analyses. Conclusion: These results suggest that honokiol may act as a potent anti-inflanunatory agent with multipotential activities due to an inhibitory effect on the PI3K/Akt pathway. |
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Bibliography: | macrophages and lymphocytes honokiol magnolol honokiol; magnolol; anti-inflammatory effects; macrophages and lymphocytes; phosphoinositide 3-kinase/Akt pathway anti-inflammatory effects R285 phosphoinositide 3-kinase/Akt pathway 31-1347/R ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1671-4083 1745-7254 |
DOI: | 10.1111/j.1745-7254.2008.00725.x |