Molecular and Cellular Biochemistry

, Volume 407, Issue 1–2, pp 89–95 | Cite as

Anti-inflammatory effect of procyanidin B1 on LPS-treated THP1 cells via interaction with the TLR4–MD-2 heterodimer and p38 MAPK and NF-κB signaling

  • Jing Xing
  • Rui Li
  • Nan Li
  • Jian Zhang
  • Yueqing Li
  • Ping Gong
  • Dongna Gao
  • Hui Liu
  • Yu ZhangEmail author


Anti-inflammatory effects of procyanidin B1 have been documented; however, the molecular mechanisms that are involved have not been fully elucidated. Molecular docking models were applied to evaluate the binding capacity of lipopolysaccharide (LPS) and procyanidin B1 with the toll-like receptor (TLR)4/myeloid differentiation factor (MD)-2 complex. LPS-induced production of the proinflammatory cytokine tumor necrosis factor (TNF)-α in a human monocyte cell line (THP1) was measured by ELISA. mRNA expression of MD-2, TLR4, TNF receptor-associated factor (TRAF)-6, and nuclear factor (NF)-κB was measured by real-time PCR with or without an 18-h co-treatment with procyanidin B1. In addition, protein expression of phosphorylated p38 mitogen-activated protein kinase (MAPK) and NF-κB was determined by Western blotting. Structural modeling studies identified Tyr296 in TLR4 and Ser120 in MD-2 as critical sites for hydrogen bonding with procyanidin B1, similar to the sites occupied by LPS. The production of TNF-α was significantly decreased by procyanidin B1 in LPS-treated THP1 cells (p < 0.05). Procyanidin B1 also significantly suppressed levels of phosphorylated p38 MAPK and NF-κB protein, as well as mRNA levels of MD-2, TRAF-6, and NF-κB (all p < 0.05). Procyanidin B1 can compete with LPS for binding to the TLR4–MD-2 heterodimer and suppress downstream activation of p38 MAPK and NF-κB signaling pathways.


Anti-inflammatory LPS Procyanidin B1 THP1 cells TLR4–MD-2 heterodimer 



This study was supported by the Young Starting Foundation of the First Affiliated Hospital, Dalian Medical University (QN2012008) and the 2013 Dalian Science and Technology Planning Project (guidance project).

Conflict of interest

The authors do not have any conflicts of interest to declare.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Jing Xing
    • 1
  • Rui Li
    • 1
  • Nan Li
    • 1
  • Jian Zhang
    • 1
  • Yueqing Li
    • 2
  • Ping Gong
    • 1
  • Dongna Gao
    • 1
  • Hui Liu
    • 1
  • Yu Zhang
    • 1
    Email author
  1. 1.Emergency DepartmentFirst Affiliated Hospital of Dalian Medical UniversityDalianChina
  2. 2.College of Pharmaceutical Science and TechnologyDalian University of TechnologyDalianChina

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