Pycnogenol attenuates atherosclerosis by regulating lipid metabolism through the TLR4-NF-κB pathway.

Abstract

Atherosclerosis is a leading cause of death worldwide and is characterized by lipid-laden foam cell formation. Recently, pycnogenol (PYC) has drawn much attention because of its prominent effect on cardiovascular disease (CVD). However, its protective effect against atherosclerosis and the underlying mechanism remains undefined. Here PYC treatment reduced areas of plaque and lipid deposition in atherosclerotic mice, concomitant with decreases in total cholesterol and triglyceride levels and increases in HDL cholesterol levels, indicating a potential antiatherosclerotic effect of PYC through the regulation of lipid levels. Additionally, PYC preconditioning markedly decreased foam cell formation and lipid accumulation in lipopolysaccharide (LPS)-stimulated human THP-1 monocytes. A mechanistic analysis indicated that PYC decreased the lipid-related protein expression of adipose differentiation-related protein (ADRP) and adipocyte lipid-binding protein (ALBP/aP2) in a dose-dependent manner. Further analysis confirmed that PYC attenuated LPS-induced lipid droplet formation via ADRP and ALBP expression through the Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) pathway, because pretreatment with anti-TLR4 antibody or a specific inhibitor of NF-κB (PDTC) strikingly mitigated the LPS-induced increase in ADRP and ALBP. Together, our results provide insight into the ability of PYC to attenuate bacterial infection-triggered pathological processes associated with atherosclerosis. Thus PYC may be a potential lead compound for the future development of antiatherosclerotic CVD therapy.

• Authors: Hong Luo, Jing Wang, Chenhui Qiao, Ning Ma, Donghai Liu, Weihua Zhang
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 47 Pg. e191 (Oct 23 2015) ISSN: 2092-6413 [Electronic] United States
• PMID: 26492950 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Flavonoids
• NF-kappa B
• Plant Extracts
• Toll-Like Receptor 4
• pycnogenols

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Atherosclerosis (drug therapy, immunology, metabolism, pathology)
• Cell Line
• Flavonoids (therapeutic use)
• Foam Cells (drug effects, immunology, pathology)
• Humans
• Lipid Metabolism (drug effects)
• Male
• Mice
• NF-kappa B (immunology)
• Plant Extracts
• Signal Transduction (drug effects)
• Toll-Like Receptor 4 (immunology)