Suppression of inflammatory responses by handelin, a guaianolide dimer from Chrysanthemum boreale, via downregulation of NF-κB signaling and pro-inflammatory cytokine production.
JOURNAL OF NATURAL PRODUCTS(2014)
Abstract
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 E-2 (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) and the nuclear factor-kappa B (NF-kappa B) and ERK/JNK signaling pathways were investigated in vitro. Compound 1 inhibited lipopolysaccharide (LPS)-induced production of NO and PGE(2) in cultured mouse macrophage RAW 264.7 cells. The suppression of NO and PGE(2) 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-alpha and IL-1 beta 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-kappa B was determined in RAW 264.7 cells. Compound 1 inhibits the binding activity of NF-kappa B into the nuclear proteins. The transcriptional activity of NF-kappa B stimulated with LPS was also suppressed by 1, which coincided with the inhibition of I kappa 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 beta was also inhibited by 1 in a carrageenan-induced paw edema model. These findings suggest that the suppression of NF-kappa B activation and pro-inflammatory cytokine production may be a plausible mechanism of action for the anti-inflammatory activity of handelin.
MoreTranslated text
Key words
inflammatory responses,handelin,guaianolide dimer,pro-inflammatory
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined