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


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.


Macrophages Anti-inflammation LPS Liver injury NF-κB MAPKs 



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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