Paeoniflorin inhibits VSMCs proliferation and migration by arresting cell cycle and activating HO-1 through MAPKs and NF-κB pathway.

Abstract

The proliferation, migration and inflammation of vascular smooth muscle cells (VSMCs) contributes to the pathogenesis and progression of atherosclerosis. Paeoniflorin (PF) as active compound in the Rhizoma Atractylodes macrocephala has been used for various diseases like cancer, splenic asthenia, anaphylaxis and anorexia. This study aimed to explore whether and how PF regulated the inflammation, proliferation and migration of VSMCs under ox-LDL stimulation. Here, we found that PF dose-dependently inhibited ox-LDL-induced VSMCs proliferation and migration, and decreased inflammatory cytokines and chemokine overexpression. Mechanistically, PF prevented p38, ERK1/2 and NF-κB phosphorylation, and arrested cell cycle in S phase. Meanwhile, PF regulated the HO-1 and PCNA expression. Furthermore, PF blocked the foam cell formation in macrophages induced by ox-LDL. These results indicate that PF antagonizes the ox-LDL-induced VSMCs proliferation, migration and inflammation through activation of HO-1, cell cycle arrest and then suppression of p38, ERK1/2/MAPK and NF-κB signaling pathways.

• Authors: Weifeng Li, Wenbing Zhi, Fang Liu, Jinmeng Zhao, Qing Yao, Xiaofeng Niu
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 54 Pg. 103-111 (Jan 2018) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 29121532 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Glucosides
• Interleukin-6
• Membrane Proteins
• Monoterpenes
• NF-kappa B
• Tumor Necrosis Factor-alpha
• peoniflorin
• Heme Oxygenase-1
• Hmox1 protein, mouse
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Atherosclerosis (drug therapy)
• Cell Cycle Checkpoints (drug effects)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Enzyme Activation
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Glucosides (therapeutic use)
• Heme Oxygenase-1 (metabolism)
• Humans
• Interleukin-6 (metabolism)
• Macrophages (immunology)
• Male
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred Strains
• Monoterpenes (therapeutic use)
• Muscle, Smooth, Vascular (drug effects)
• NF-kappa B (metabolism)
• Signal Transduction
• Tumor Necrosis Factor-alpha (metabolism)