Kim Byung Hun, Cho Jae Youl
School of Bioscience and Biotechnology, and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea.
Acta Pharmacol Sin. 2008 Jan;29(1):113-22. doi: 10.1111/j.1745-7254.2008.00725.x.
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.
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.
Honokiol strongly inhibited various inflammatory responses, such as: (i) the upregulation of nitric oxide (NO), prostaglandin E2 and TNF-alpha production and costimulatory molecule CD80 induced by lipopolysaccharide (LPS); (ii) the functional activation of beta1-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-alpha, 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.
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.
在本研究中，我们探究了厚朴酚对由单核细胞/巨噬细胞（U937/RAW264.7细胞）和淋巴细胞（脾淋巴细胞和CTLL-2细胞）介导的各种炎症事件的调节作用及其可能的作用机制。
为了研究调节作用，使用了各种细胞系和原代细胞（U937、RAW264.7、CTLL-2细胞和脾淋巴细胞），并选择了各种炎症事件，如炎症介质的产生、细胞黏附、细胞增殖和早期信号级联反应。
厚朴酚强烈抑制各种炎症反应，例如：（i）脂多糖（LPS）诱导的一氧化氮（NO）、前列腺素E2和肿瘤坏死因子-α产生以及共刺激分子CD80的上调；（ii）通过U937细胞-细胞和细胞-纤连蛋白黏附评估的β1整合素（CD29）的功能激活；（iii）LPS、植物血凝素A（PHA）、伴刀豆球蛋白A或白细胞介素（IL）-2刺激的淋巴细胞和CD8+ CTLL-2细胞增殖的增强；以及（iv）诱导型NO合酶、肿瘤坏死因子-α、环氧化酶-2、IL-12和单核细胞趋化蛋白（MCP）-1的转录上调。根据药理学、生化和功能分析，厚朴酚的这些抗炎作用似乎是通过中断早期激活的细胞内信号分子磷酸肌醇3激酶（PI3K）/Akt介导的，而不是通过Src、细胞外信号调节激酶和p38介导。
这些结果表明，由于对PI3K/Akt途径的抑制作用，厚朴酚可能作为一种具有多种潜在活性的强效抗炎剂。
