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 Zhang

Mol Cell Biochem. 2015 Sep;407(1-2):89-95.

PMID: 26037075

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP20315257	Procyanidin B1		20315-25-7	Price