Silymarin Constituents Enhance ABCA1 Expression in THP-1 Macrophages

Springer Science and Business Media LLC - Tập 21 Số 1 - Trang 55
Limei Wang1, Susanne Rotter1, Angela Ladurner1, Elke H. Heiß1, Nicholas H. Oberlies2, Verena M. Dirsch1, Atanas G. Atanasov1
1Department of Pharmacognosy, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria
2Department of Chemistry & Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, USA

Tóm tắt

Silymarin is a hepatoprotective mixture of flavonolignans and flavonoids extracted from the seeds of milk thistle (Silybum marianum L. Gaertn). This study investigates the effect of major bioactive constituents from silymarin, silybin A, silybin B, isosilybin A, isosilybin B, silydianin, silychristin, isosilychristin, and taxifolin, on the expression of ABCA1, an important cholesterol efflux transporter, in THP-1-derived macrophages. Four of the studied compounds, isosilybin A, silybin B, silychristin and isosilychristin, were found to significantly induce ABCA1 protein expression without affecting cell viability. Moreover, isosilybin A, a partial PPARγ agonist, was found to promote cholesterol efflux from THP-1 macrophages in a concentration-dependent manner. These findings first show ABCA1 protein up-regulating activity of active constituents of silymarin and provide new avenues for their further study in the context of cardiovascular disease.

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Tài liệu tham khảo

Atanasov, 2015, Discovery and resupply of pharmacologically active plant-derived natural products: A review, Biotechnol. Adv., 33, 1582, 10.1016/j.biotechadv.2015.08.001

Kvasnicka, 2003, Analysis of the active components of silymarin, J. Chromatogr. A, 990, 239, 10.1016/S0021-9673(02)01971-4

Gazak, 2007, Silybin and silymarin—New and emerging applications in medicine, Curr. Med. Chem., 14, 315, 10.2174/092986707779941159

Weidmann, 2012, Dihydroquercetin: More than just an impurity?, Eur. J. Pharmacol., 684, 19, 10.1016/j.ejphar.2012.03.035

Lee, 2003, Molecular structure and stereochemistry of silybin a, silybin b, isosilybin a, and isosilybin b, isolated from silybum marianum (milk thistle), J. Nat. Prod., 66, 1171, 10.1021/np030163b

Saller, 2001, The use of silymarin in the treatment of liver diseases, Drugs, 61, 2035, 10.2165/00003495-200161140-00003

Skottova, 1998, Silymarin as a potential hypocholesterolaemic drug, Physiol. Res., 47, 1

Krecman, 1998, Silymarin inhibits the development of diet-induced hypercholesterolemia in rats, Planta Med., 64, 138, 10.1055/s-2006-957391

Skottova, 2003, Effects of polyphenolic fraction of silymarin on lipoprotein profile in rats fed cholesterol-rich diets, Pharmacol. Res., 47, 17, 10.1016/S1043-6618(02)00252-9

Sobolova, 2006, Effect of silymarin and its polyphenolic fraction on cholesterol absorption in rats, Pharmacol. Res., 53, 104, 10.1016/j.phrs.2005.09.004

Fried, 2012, Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis c unsuccessfully treated with interferon therapy: A randomized controlled trial, JAMA, 308, 274, 10.1001/jama.2012.8265

Oram, 2001, Abca1: The gatekeeper for eliminating excess tissue cholesterol, J. Lipid Res., 42, 1173, 10.1016/S0022-2275(20)31566-2

Oram, 2000, Tangier disease and abca1, BBA Mol. Cell Biol. Lipids, 1529, 321, 10.1016/S1388-1981(00)00157-8

Clee, 2002, Association between increased arterial-wall thickness and impairment in abca1-driven cholesterol efflux: An observational study, Lancet, 359, 37, 10.1016/S0140-6736(02)07277-X

Phillips, 2014, Molecular mechanisms of cellular cholesterol efflux, J. Biol. Chem., 289, 24020, 10.1074/jbc.R114.583658

Chawla, 2001, A ppar gamma-lxr-abca1 pathway in macrophages is involved in cholesterol efflux and atherogenesis, Mol. Cell, 7, 161, 10.1016/S1097-2765(01)00164-2

Atanasov, 2014, Identification of isosilybin a from milk thistle seeds as an agonist of peroxisome proliferator-activated receptor gamma, J. Nat. Prod., 77, 842, 10.1021/np400943b

Wang, 2014, Natural product agonists of peroxisome proliferator-activated receptor gamma (ppar-gamma): A review, Biochem. Pharmacol., 92, 73, 10.1016/j.bcp.2014.07.018

Wilson, 2000, Investigation of the alamar blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity, Eur. J. Biochem., 267, 5421, 10.1046/j.1432-1327.2000.01606.x

Ladurner, 2012, 2-(2,4-dihydroxyphenyl)-5-(E)-propenylbenzofuran promotes endothelial nitric oxide synthase activity in human endothelial cells, Biochem. Pharmacol., 84, 804, 10.1016/j.bcp.2012.06.029

Ozasa, 2011, Pioglitazone enhances cholesterol efflux from macrophages by increasing abca1/abcg1 expressions via ppar gamma/lxr alpha pathway: Findings from in vitro and ex vivo studies, Atherosclerosis, 219, 141, 10.1016/j.atherosclerosis.2011.07.113

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