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Archives of Pharmacal Research

, Volume 41, Issue 3, pp 314–323 | Cite as

Dihydropyranoaurone compound damaurone D inhibits LPS-induced inflammation and liver injury by inhibiting NF-κB and MAPK signaling independent of AMPK

  • Zheng Wang
  • Sun-O Ka
  • Young Taek Han
  • Eun Ju Bae
Research Article

Abstract

Recently, we reported the synthesis of damaurone D (DD), originally derived from Rosa damascene, and its anti-inflammatory effect in macrophages. Here, we investigated the molecular mechanism underlying the anti-inflammatory effect of DD in macrophages and further tested whether DD is protective against lipopolysaccharide (LPS)-induced liver injury. DD inhibited LPS-stimulated expression of pro-inflammatory genes and cytokine/chemokine secretion in a concentration-dependent manner in RAW 264.7 cells and thioglycolate-elicited mouse peritoneal macrophages. DD suppressed LPS-stimulated nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, as demonstrated by reduction in IκB kinase α/β phosphorylation, IκBα degradation, and levels of phosphorylated ERK, JNK, and p38 MAPK. The luciferase reporter activity of NF-κB and activator protein 1 was also attenuated by DD pretreatment. Furthermore, DD treatment induced AMP-activated protein kinase (AMPK) activation in cells and mouse liver, although the anti-inflammatory effect of DD was similar in dominant-negative AMPK-overexpressing cells. Lastly, DD-treated mice were protected against LPS-induced acute liver injury, based on morphologic and immunohistochemical observations; reduction in the plasma levels of aspartate aminotransferase, TNF-α, and MCP-1; and a decrease in inflammatory gene expression. In summary, our findings indicate that DD can protect against LPS-stimulated inflammation and liver injury at least partly by suppression of NF-κB and MAPK signaling pathways.

Keywords

Macrophages Anti-inflammation LPS Liver injury NF-κB MAPKs 

Notes

Acknowledgements

This work was partially supported by the research fund of Woosuk University.

Compliance with ethical standards

Conflict of interest

The authors have declared that no conflict of interest exists.

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Copyright information

© The Pharmaceutical Society of Korea 2017

Authors and Affiliations

  • Zheng Wang
    • 1
  • Sun-O Ka
    • 2
  • Young Taek Han
    • 3
  • Eun Ju Bae
    • 1
  1. 1.College of PharmacyWoosuk UniversityWanjuRepublic of Korea
  2. 2.Department of BiochemistryChonbuk National University Medical SchoolJeonjuRepublic of Korea
  3. 3.College of PharmacyDankook UniversityCheonanRepublic of Korea

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