Curcumin inhibits cellular cholesterol accumulation by regulating SREBP-1/caveolin-1 signaling pathway in vascular smooth muscle cells

• Published in: Acta pharmacologica Sinica Vol. 29; no. 5; pp. 555 - 563
• Main Authors: Yuan, Hao-Yu, Kuang, Shuang-Yu, Zheng, Xing, Ling, Hong-Yan, Yang, Yun-Bo, Yan, Peng-Ke, Li, Kai, Liao, Duan-Fang
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.05.2008
• Subjects: Animals; Caveolin 1 - metabolism; Cells, Cultured; Cholesterol - metabolism; Curcumin - pharmacology; Dose-Response Relationship, Drug; Fluorescent Antibody Technique, Indirect; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Smooth, Vascular - metabolism; Random Allocation; Rats; Signal Transduction; SREBP-1; Sterol Regulatory Element Binding Protein 1 - metabolism; Time Factors; 姜黄色素; 胆固醇积聚; 血管平滑肌细胞
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1111/j.1745-7254.2008.00783.x

Aim： To investigate the protective effect and the possible mechanism of curcumin on anti-atherosclerosis. Methods： Morphological changes of atherosclerotic lesions taken from apoE knockout （apoE^-/-） mice were determined by hematoxylineosin staining. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC. The protein expression of caveolin- 1 was quantified by Western blotting. Translocation and the expression of sterol response element-binding protein-1 （SREBP-1） were indirectly detected by an immunofluorescence analysis. Results： The administration of 20 mg.kg^-1.d^-1 curcumin to apoE^-/- mice for 4 months induced a 50% reduction of atherosclerotic lesions and yielded a 5- fold increase in the caveolin-1 expression level as compared to the model group. Rat vascular smooth muscle cells （VSMC） pretreated with 50 mg.L^-1 ox-lipid density lipoprotein（ox-LDL） for 48 h increased cellular lipid contents, and stimulated SREBP-1 translocation, but decreased the caveolin-1 expression level. Lipid-loaded cells exposed to curcumin at various concentrations （12.5, 25, and 50 μmol.L^-1） for different durations （0, 6, 12, 24, and 48 h） significantly diminished the number and area of cellular lipid droplets, total cholesterol, cholesterol ester, and free choles- terol accompanying the elevation of the caveolin- 1 expression level （approximately 3-fold）; the translocation of SREBP-1 from the cytoplasm to the nucleus was inhibited compared with the models. Lipid-loaded VSMC exposed to N-acetylLeu-Leu-norleucinal, a SREBP- 1 protease inhibitor, showed increased nuclear trans- location of SREBP-1, reduced caveolin-1 expression level, and upregulated cellu- lar lipid levels. Condusion： Curcumin inhibits ox-LDL-induced cholesterol accu- mulation in cultured VSMC through increasing the caveolin-1 expression via the inhibition of nuclear translocation of SREBP- 1.