摘要：
Aim: To investigate the mechanisms of anti-atherosclerotic action of ezetimibe in rat vascular smooth muscle cells (VSMCs) in vitro. Methods: VSMCs of SD rats were cultured in the presence of Chol:MβCD (10 μg/mL) for 72 h, and intracellular lipid droplets and cholesterol levels were evaluated using Oil Red O staining, HPLC and Enzymatic Fluorescence Assay, respectively. The expression of caveolin-1，sterol response element-binding protein-1 (SREBP-1) and ERK1/2 were analyzed using Western blot assays. Translocation of SREBP-1 and ERK1/2 was detected with immunofluorescence. Results: Treatment with Chol: MβCD dramatically increased the cellular levels of total cholesterol (TC)，cholesterol ester (CE) and free cholesterol (FC) in VSMCs, which led to the formation of foam cells. Furthermore, Chol:MβCD treatment significantly decreased the expression of caveolin-1, and stimulated the expression and nuclear translocation of SREBP-1 in VSMCs. Co-treatment with ezetimibe (3 μmol/L) significantly decreased the cellular levels of TC, CE and FC, which was accompanied by elevation of caveolin-1 expression, and by a reduction of SREBP-1 expression and nuclear translocation. Co-treatment with ezetimibe dose-dependently decreased the expression of phosphor-ERK1/2 (p-ERK1/2) in VSMCs. The ERK1/2 inhibitor PD98059 (50 μmol/L) altered the cholesterol level and the expression of p-ERK1/2, SREBP-1 and caveolin-1 in the same manner as ezetimibe did. Conclusion: Ezetimibe suppresses cholesterol accumulation in rat VSMCs in vitro by regulating SREBP-1 and caveolin-1 expression, possibly via the MAPK signaling pathway.
作者机构：
[LI Juan; LI Shun-Xiang] School of Pharmacy, Hunan University of Chinese Medicine;[ZHAO Jian-ping] The National Center for Natural Products Research
会议名称：
第十四届全国中药和天然药物学术研讨会暨第十三届中药全球化联盟大会
会议时间：
2014-8-27
会议地点：
北京
会议主办单位：
中国药学会
会议论文集名称：
第十四届全国中药和天然药物学术研讨会暨第十三届中药全球化联盟大会论文集
关键词：
Acorus calamus Linn.;sesquiterpenoids
摘要：
Objective To study the chemical components from the ethanol extract of rhizomas Acori Calami from Hunan Province.Methods Components were isolated and purified through various chromatographic methods and recrystallization,and identified by spectroscopic data.Results 30 sesquiterpenoids were isolated and indentified as follows:6 guaiane-type sesquiterpenoids,11 cadinane-type sesquiterpenoids,3 elemane-type sesquiterpenoids,2eudesmane-type sesquiterpenoids,3 acorane-type sesquiterpenoids,2aromadendrane-type sesquiterpenoids,1 prelacinane-type sesquiterpene,1oppositane-type sesquiterpene and 1 oplopanane-type sesquiterpene.Conclusion 10 compounds were new sesquiterpenoids.4 compounds were isolated from Acorus genus for the first time.
作者机构：
[Li, Shun-Xiang; Yang, Yun-Bo; Zheng, Xi-Long; Liao, Duan-Fang; Qin, Li] Hunan Univ Chinese Med, Sch Pharm, Div Stem Cell Regulat & Applicat, Changsha 410208, Hunan, Peoples R China.;[Yang, Yun-Bo; Zhu, Neng] Cent S Univ, Xiang Ya Hosp 2, Changsha, Hunan, Peoples R China.;[Qin, Li] South China Univ, Inst Pharm & Pharmacol, Hengyang, Hunan, Peoples R China.;[Zhu, Neng] South China Univ, Affiliated Hosp 2, Hengyang, Hunan, Peoples R China.;[Yang, Yun-Bo; Yang, Yi-Xin] Western Univ, London Hlth Sci Ctr, Matthew Mailing Ctr Translat Transplantat Studies, London, ON, Canada.
通讯机构：
[Liao, Duan-Fang] H;Hunan Univ Chinese Med, 1 Xiangzui Rd, Changsha 410208, Hunan, Peoples R China.
关键词：
Ezetimibe;Inflammation;Mitogen-activated protein kinase;Nuclear factor kappa-light-chain-enhancer of activated B cells;Macrophage
摘要：
Inflammation plays a crucial role in atherosclerosis. Monocytes/ macrophages are involved in the inflammatory process during atherogenesis. Here, we performed daily gavage of ezetimibe in apolipoprotein E-deficient mice fed with a high-fat diet and found that ezetimibe administration decreased the level of C-reactive protein significantly. To investigate the potential molecular mechanism, we employed microarray analysis on the cultured macrophages treated with Chol: M beta CD in the presence or absence of ezetimibe. We found that ezetimibe dramatically down-regulated the expression of the tumor necrosis factor-a (TNF-alpha) gene. Consistent with the microarray results, TNF-alpha protein levels were inhibited by ezetimibe. Moreover, ezetimibe suppressed the promoter activity of TNF-alpha but not TNF-alpha lacking the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) binding domain in THP-1 cells treated with phorbol myristate acetate and Chol: M beta CD. Furthermore, treatment of THP-1 macrophages with ezetimibe resulted in the degradation of l kappa B and subsequently inhibited nuclear translocation of NF-kappa B and its transcriptional activity. Inhibition of the mitogen-activated protein kinase (MAPK) pathway using PD98059 attenuated the reduction effect of ezetimibe on the expression of NF-kappa B. Collectively, our results demonstrated that the anti-inflammatory properties of ezetimibe in THP-1 macrophages are, at least in part, through suppression of NF-kappa B activation via the MAPK pathway. These data provide direct evidence for the potential application of ezetimibe in the prevention and treatment of inflammatory diseases. (C) 2014 S. Karger AG, Basel
