Anti-atherosclerotic potential of baicalin mediated by promoting cholesterol efflux from macrophages via the PPARγ-LXRα-ABCA1/ABCG1 pathway

• Published in: Biomedicine & pharmacotherapy Vol. 83; pp. 257 - 264
• Main Authors: He, Xin-Wei, Yu, Dan, Li, Wei-Ling, Zheng, Zhou, Lv, Chen-Ling, Li, Cai, Liu, Peng, Xu, Chun-Qiang, Hu, Xiao-Fei, Jin, Xiao-Ping
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.10.2016
• Subjects: Animals; Atherosclerosis; Atherosclerosis - blood; Atherosclerosis - drug therapy; Atherosclerosis - metabolism; ATP Binding Cassette Transporter 1 - metabolism; ATP Binding Cassette Transporter, Sub-Family G, Member 1 - metabolism; Baicalin; Biological Transport - drug effects; Body Weight - drug effects; Carotid Arteries - drug effects; Carotid Arteries - pathology; Cell Line; Cholesterol - metabolism; Cholesterol efflux; Flavonoids - pharmacology; Flavonoids - therapeutic use; Foam Cells - drug effects; Foam Cells - pathology; Humans; Internal Medicine; Lipids - blood; Liver X Receptors - metabolism; LXRα; Macrophages - drug effects; Macrophages - metabolism; Male; Medical Education; Models, Biological; PPAR gamma - metabolism; PPARγ; Rabbits; RNA, Small Interfering - metabolism; scavenger receptor class B type I; ATP binding cassette transporters A1; SR-BI; low density lipoprotein; ATP binding cassette transporters G1; LXRα; cluster of differentiation 36; total cholesterol; class A scavenge receptors; HDL; LDL; Atherosclerosis; PPARg; CD36; SR-A s; Baicalin; Cholesterol efflux; ABCA1; Oxidized-low density lipoprotein; Liver X receptor alpha; ox-LDL; Triglyceride; PPARγ; TC; TG; LXRa; high density lipoprotein; peroxisome proliferator-activated receptor gamma; ABCG1; SR-As
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2016.06.046

Abstract Background Atherosclerosis (AS) is associated with severe cardiovascular disease. The anti-inflammatory, anti-oxidation, and lipid regulating properties of baicalin suggest potential as an anti-atherosclerotic agent. We therefore investigated whether baicalin can protect against the development of atherosclerosis in an AS rabbit model and explored the underling mechanisms in THP-1 macrophages. Methods and results In vivo, treatment with baicalin markedly decreased atherosclerotic lesion sizes and lipid accumulation in AS rabbit carotid arteries. Western blotting revealed that the protein expression levels of both peroxisome proliferator-activated receptor gamma (PPARγ) and liver X receptor alpha (LXRα) were up-regulated in the baicalin group compared with the model group. In vitro, baicalin restricted oxidized-low density lipoprotein (ox-LDL)-induced intracellular lipid accumulation and foam cell formation in THP-1 macrophages. Molecular data showed that baicalin significantly increased the expression levels of PPARγ, LXRα, ATP binding cassette transporters (ABC) A1 and ABCG1. Cell transfection experiments (including PPARγ and LXRα siRNAs) suggested that the effects of baicalin are mediated by the PPARγ-LXRα signalling pathway, which stimulates the expression of ABCA1 and ABCG1. Conclusion These results suggest that baicalin potentially exerts anti-atherosclerosis effects, possibly through the PPARγ-LXRα-ABCA1/ABCG1 pathway, by promoting efflux of cholesterol from macrophages and delaying the formation of foam cells.