Ellipticine Conveys Protective Effects to Lipopolysaccharide-Activated Macrophages by Targeting the JNK/AP-1 Signaling Pathway
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Ellipticine, a natural product from Ochrosia elliptica, has been broadly investigated for its anticancer effects. Although inflammation has been clearly identified as a key factor in the onset and progression of cancer, the relationship between ellipticine and inflammation remains unknown. Hence, the aims of the present study were to assess the effects of ellipticine on the inflammatory responses to lipopolysaccharide (LPS)-induced macrophages and to potentially identify the underlying mechanisms involved. Viability testing showed that ellipticine was not significantly toxic to Raw264.7 cells and actually conveyed protective effects to LPS-stimulated Raw264.7 cells and human peripheral blood monocytes by decreasing the secretion of inflammatory factors (TNF-α and IL-6). The results of western blot analysis and electrophoretic mobility shift assays showed that ellipticine markedly suppressed LPS-induced activation of the JNK/AP-1 (c-Fos and c-Jun) signaling pathway, but not ERK/p38/NF-κB pathway (p65 and p50) activation. Furthermore, ellipticine reduced the inflammatory response and mortality in a mouse model of LPS-induced endotoxic shock. Collectively, these data indicate that ellipticine may be a potential therapeutic agent for the treatment of inflammation-associated diseases.
KEY WORDSellipticine inflammation macrophages JNK/AP-1
This work was supported by grants from the National Natural Science Foundation of China (grant no. 81871612), the Fund of State Key Laboratory of Trauma, Burn, and Combined Injury (grant no. SKLJYJF03, SKLZZ201709), and the Fund of Basic Science and Frontier Q8 Technology Research of Chongqing (grant no. cstc2017jcyjAX0159).
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Conflict of interest
The authors declare that they have no conflict of interest.
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