کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5554429 | 1558868 | 2017 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Fumigaclavine C exhibits anti-inflammatory effects by suppressing high mobility group box protein 1 relocation and release Fumigaclavine C exhibits anti-inflammatory effects by suppressing high mobility group box protein 1 relocation and release](/preview/png/5554429.png)
A previous study demonstrated that Fumigaclavine C (FC) had a potential immunosuppressive activity against concanavalin A-induced hepatitis in mice. However, the precise mechanisms of the anti-inflammatory and hepatoprotective effects of FC are incompletely delineated. This study further investigated the protective effects of FC on lipopolysaccharide (LPS)-induced murine RAW264.7 cells and the underlying molecular mechanism in liver kupffer cells. FC differentially attenuated the production of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interferon gamma (IFN-γ), and high mobility group box protein 1 (HMGB-1). Intriguingly, FC significantly suppressed LPS-induced HMGB-1 nucleo-cytoplasmic shuttling relocation and release. FC notably decreased the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), protein kinase C beta II (PKCβII), and protein kinase C gamma (PKCγ). PKCβII/γ played an important part in this signaling pathway cascade. Furthermore, the docking simulation revealed that FC could directly bind to the HMGB-1 B box interfering with Lys90 and Leu145. All of these results indicated that FC exhibited anti-inflammatory and hepatoprotective effects through suppressing HMGB-1 relocation and release by interfering with Lys90 and Leu145.
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Journal: European Journal of Pharmacology - Volume 812, 5 October 2017, Pages 234-242