Abstract
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), prostaglandin 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-inflammatory agent with multipotential activities due to an inhibitory effect on the PI3K/Akt pathway.
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This work was supported by a Korea Research Foundation Grant (KRF-2006-C00455 to Jae Youl Cho).
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Kim, B., Cho, J. Anti-inflammatory effect of honokiol is mediated by PI3K/Akt pathway suppression. Acta Pharmacol Sin 29, 113–122 (2008). https://doi.org/10.1111/j.1745-7254.2008.00725.x
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DOI: https://doi.org/10.1111/j.1745-7254.2008.00725.x
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