Suppression of Inflammatory Responses by Handelin, a Guaianolide Dimer from Chrysanthemum boreale, via Downregulation of NF-魏B Signaling and Pro-inflammatory Cytokine Production

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• 作者：Yuna Pyee ; Hwa-Jin Chung ; Tae Jun Choi ; Hyen Joo Park ; Ji-Young Hong ; Ju Sun Kim ; Sam Sik Kang ; Sang Kook Lee
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：April 25, 2014
• 年：2014
• 卷：77
• 期：4
• 页码：917-924
• 全文大小：453K
• 年卷期：v.77,no.4(April 25, 2014)
• ISSN：1520-6025

文摘

The anti-inflammatory activity of handelin (1), a guaianolide dimer from Chrysanthemum boreale flowers, was evaluated in vivo, and the effects on mediators nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor-伪 (TNF-伪), and interleukin-1尾 (IL-1尾) and the nuclear factor-魏B (NF-魏B) and ERK/JNK signaling pathways were investigated in vitro. Compound 1 inhibited lipopolysaccharide (LPS)-induced production of NO and PGE₂ in cultured mouse macrophage RAW 264.7 cells. The suppression of NO and PGE₂ production by 1 was correlated with the downregulation of mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Compound 1 also suppressed the induction of pro-inflammatory cytokines TNF-伪 and IL-1尾 in LPS-stimulated RAW 264.7 cells. To further clarify the transcriptional regulatory pathway in the expression of iNOS and COX-2 by 1, the role of NF-魏B was determined in RAW 264.7 cells. Compound 1 inhibits the binding activity of NF-魏B into the nuclear proteins. The transcriptional activity of NF-魏B stimulated with LPS was also suppressed by 1, which coincided with the inhibition of I魏B degradation. Compound 1 also suppressed the activation of mitogen-activated protein kinases, including ERK and JNK signaling. In addition, the LPS-stimulated upregulation of miRNA-155 expression was suppressed by 1. The oral administration of 1 inhibited acute inflammation in carrageenan-induced paw and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema models. The serum level of IL-1尾 was also inhibited by 1 in a carrageenan-induced paw edema model. These findings suggest that the suppression of NF-魏B activation and pro-inflammatory cytokine production may be a plausible mechanism of action for the anti-inflammatory activity of handelin.