Although various physiological activities of compounds obtained from Paeonia lactiflora have been reported, the effects of P. lactiflora extract (PLE) on early atherosclerosis remain unclear. Therefore, in this study, we investigated the in vitro and in vivo antiatherosclerosis and in vitro antioxidant effects of PLE and its compounds. PLE suppresses the tumor necrosis factor (TNF)-α-induced capacity of THP-1 cells to adhere to human umbilical vein endothelial cells (HUVECs), vascular cell adhesion molecule (VCAM)-1 expression, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in HUVECs. PLE also suppresses TNF-α-induced nuclear translocation of NF-κB p65 from cytosol as well as the enhanced TNFA and C-C motif chemokine ligand 2 (CCL2) mRNA expression in HUVECs. We identified and quantified the following PLE compounds using high-performance liquid chromatography with diode array detection: methyl gallate, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, benzoic acid, benzoylpaeoniflorin, and paeonol. Among these, methyl gallate had the strongest inhibitory effect on monocyte adherence to TNF-α-induced HUVECs and the VCAM-1 expression. Reverse transcriptase real-time quantitative polymerase chain reaction showed that PLE compounds had a dissimilar inhibition effect on TNF-α-induced mRNA expression levels of CCL2, TNFA, and IL6 in HUVECs. Except for paeonol, the compounds inhibited lipopolysaccharide (LPS)-induced reactive oxygen species production in RAW264.7 cells. In vivo, oral administration of PLE improved TNF-α-induced macrophage infiltration to the vascular endothelium and expression of VCAM-1, as well as IL6 and TNFA gene expression in the main artery of mice. PLE could be useful as a nutraceutical material against early atherosclerosis via the combined effects of its components.
Keywords: NF-κB; Paeonia lactiflora; VCAM-1; atherosclerosis; monocyte adhesion; vascular inflammation.