, Volume 39, Issue 1, pp 434–446 | Cite as

Anti-inflammatory and Anti-oxidative Activities of Paeonol and Its Metabolites Through Blocking MAPK/ERK/p38 Signaling Pathway

  • Xin Jin
  • Jing Wang
  • Zi-Ming Xia
  • Chang-Hui Shang
  • Qiu-Li Chao
  • Ya-Ru Liu
  • Hua-Ying Fan
  • Da-Quan Chen
  • Feng Qiu
  • Feng Zhao
Original Article


The possible protective and curative effects of paeonol on carrageenan-induced acute hind paw edema in rats and dextran sulfate sodium (DSS)-induced colitis in mice have been evaluated. After oral administration, paeonol (20 and 40 mg/kg) reduced the edema increase in paw volumes and also the development of DSS-induced murine colitis. Furthermore, anti-inflammatory and anti-oxidant activities of paeonol (1) together with its 10 metabolites (M2~M11) were investigated by using in vitro anti-inflammatory and anti-oxidant assays. M3 and M11 exhibited significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities (with EC50 values of 93.44 and 23.24 μM, respectively). All the metabolites except M8 showed hydroxyl radical scavenging activities, and M3 and M11 were the most potent agents (with EC50 values of 336.02 and 124.05 μM, respectively). Inhibitory effects of paeonol, M2~M11 on the overproduction of nitric oxide (NO), and the release of TNF-α were also tested. M3 and M11 potently inhibited lipopolysaccharide (LPS)-induced overproduction of NO in macrophage RAW 264.7. Western blot results demonstrated that paeonol, M3, and M11 downregulated the high expression of inducible nitric oxide synthase (iNOS) and COX-2 proteins, and the effects of M3 and M11 were more potent when compared with paeonol. These findings indicated that paeonol may play anti-inflammatory and anti-oxidant roles by changing to its active metabolites after absorption. In addition, further investigations on the mechanism showed that paeonol, M3, and M11 blocked the phosphorylation of MAPK/ERK 1/2 and p38, whereas they showed no effect on the phosphorylation of JNK. The above results suggested that pre-treatment with paeonol might be an effective therapeutic intervention against inflammatory diseases including colitis.


paeonol metabolite inflammation oxidative stress MAPK 



This work was supported by the State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, and the Taishan Scholar Project to Fenghua Fu, and the Scientific and Technological Project of Yantai City, as well as by the Undergraduate Scientific and Technological Innovation Project of Yantai University.

Conflict of interest

The authors report no conflicts of interest in this work.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Xin Jin
    • 1
  • Jing Wang
    • 1
  • Zi-Ming Xia
    • 1
  • Chang-Hui Shang
    • 1
  • Qiu-Li Chao
    • 1
  • Ya-Ru Liu
    • 1
  • Hua-Ying Fan
    • 1
  • Da-Quan Chen
    • 1
  • Feng Qiu
    • 2
  • Feng Zhao
    • 1
  1. 1.School of PharmacyYantai UniversityYantaiPeople’s Republic of China
  2. 2.Tianjin State Key Laboratory of Modern Chinese Medicine, School of Chinese Materia MedicaTianjin University of Traditional Chinese MedicineTianjinPeople’s Republic of China

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