Pleiotropic effects of statins: new therapeutic targets in drug design

被引:0
作者
Onkar Bedi
Veena Dhawan
P. L. Sharma
Puneet Kumar
机构
[1] I.S.F College of Pharmacy,Department of Pharmacology
[2] Post Graduate Institute of Medical Education & Research (PGIMER),Department of Experimental Medicine and Biotechnology
[3] Post Graduate Institute of Medical Education & Research (PGIMER),Department of Pharmacology
来源
Naunyn-Schmiedeberg's Archives of Pharmacology | 2016年 / 389卷
关键词
Atherosclerotic; Statins; Pleiotropic effects; Anti-inflammatory; Rheumatoid arthritis;
D O I
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学科分类号
摘要
The HMG Co-enzyme inhibitors and new lipid-modifying agents expand their new therapeutic target options in the field of medical profession. Statins have been described as the most effective class of drugs to reduce serum cholesterol levels. Since the discovery of the first statin nearly 30 years ago, these drugs have become the main therapeutic approach to lower cholesterol levels. The present scientific research demonstrates numerous non-lipid modifiable effects of statins termed as pleiotropic effects of statins, which could be beneficial for the treatment of various devastating disorders. The most important positive effects of statins are anti-inflammatory, anti-proliferative, antioxidant, immunomodulatory, neuroprotective, anti-diabetes, and antithrombotic, improving endothelial dysfunction and attenuating vascular remodeling besides many others which are discussed under the scope of this review. In particular, inhibition of Rho and its downstream target, Rho-associated coiled-coil-containing protein kinase (ROCK), and their agonistic action on peroxisome proliferator-activated receptors (PPARs) can be viewed as the principle mechanisms underlying the pleiotropic effects of statins. With gradually increasing knowledge of new therapeutic targets of statins, their use has also been advocated in chronic inflammatory disorders for example rheumatoid arthritis (RA) and in systemic lupus erythematosus (SLE). In the scope of review, we highlight statins and their pleiotropic effects with reference to their harmful and beneficial effects as a novel approach for their use in the treatment of devastating disorders.
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页码:695 / 712
页数:17
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[1]  
Abe M(2010)The HMG-CoA reductase inhibitor pravastatin stimulates insulin secretion through organic anion transporter polypeptides Drug Metab Pharmacokinet 25 74-282
[2]  
Toyohara T(2010)Pravastatin provides antioxidant activity and protection of erythrocytes loaded primaquine Int J Med Sci 7 358-64
[3]  
Ishii A(2003)Production and purification of statins from Pleurotus ostreatus (Basidiomycetes) strains Zeitschrift für Naturforschung C 58 62-70
[4]  
Suzuki T(2001)Effect of statin therapy on C-reactive protein levels, the pravastatin inflammation/CRP evaluation (PRINCE), a randomized trial and cohort study JAMA 286 64-165
[5]  
Noguchi N(2003)Plasma concentration of C-reactive protein and the calculated Framingham Coronary Heart Disease Risk Score Circulation 108 161-559
[6]  
Akiyama Y(1995)Influence of nicotinic acid on serum cholesterol in man Arch Biochem Biophys 54 558-65
[7]  
Shiwaku HO(1905)Mechanism of action of MER-29, an inhibitor of cholesterol biosynthesis Biochem Biophys Res Commun 2 63-2192
[8]  
Nakagomi-Hagihara R(2011)The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection), a randomised placebo-controlled trial Lancet 377 2181-461
[9]  
Zheng G(2007)Effects of simvastatin and oral contraceptive agent on polycystic ovary syndrome, prospective, randomized, crossover trial J Clin Endocrinol Metab 92 456-1667
[10]  
Shibata E(2008)Statins reduce neuronal α-synuclein aggregation in in vitro models of Parkinson’s disease J Neurochem 105 1656-380