Xin-Wei He1, Dan Yu2, Wei-Ling Li3, Zhou Zheng4, Chen-Ling Lv5, Cai Li6, Peng Liu7, Chun-Qiang Xu8, Xiao-Fei Hu9, Xiao-Ping Jin1. 1. Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: doctorxinweihe@163.com. 2. Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: yd@enzemed.com. 3. Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: liwl@enzemed.com. 4. Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: zhengzhou@enzemed.com. 5. Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: 598298676@qq.com. 6. Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: licai@enzemed.com. 7. Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: xs_liup@enzemed.com. 8. Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: xucq@enzemed.com. 9. Department of Neurology, Taizhou Hospital, Affiliated Hospital of Wenzhou Medical University, Taizhou, Zhejiang, PR China. Electronic address: huxf@enzemed.com.
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.
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.