Open AccessAnti‐inflammatory effect of honokiol is mediated by PI3K/Akt pathway suppression 1
Author(s) -
KIM Byung Hun,
CHO Jae Youl
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00725.x
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , microbiology and biotechnology , wortmannin , downregulation and upregulation , chemistry , signal transduction , cd80 , cancer research , biology , biochemistry , cd40 , cytotoxic t cell , gene , in vitro
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 E 2 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.