Hypocholesterolemic atherosclerosis

Probucol, a hypocholesterolemic drug that possesses antioxidant activity, inhibits the ex vivo release of IL-1 from LPS-stimulated macrophages of mice pretreated orally with 100 mg/kg/day of this compound [94,95]. This compound has been shown to inhibit LPS-induced zinc-lowering effect, is cited as direct evidence for the inhibition of IL-1 release, and may be useful candidate for the treatment of atherosclerosis [95,96]. An amino-dithiol-one derivative (RP 54745) blocked the proliferative action of IL-1 P on murine thymocytes in vitro and also inhibited the production of IL-1 in mouse peritoneal macrophages in vitro and in vivo. The compound RP 54745 selectively inhibited the expression of IL-la and IL-1 3 mRNA while TNFa mRNA was unaffected [97, 98]. 

Hypercholesterolemia is well established as a risk factor for atherosclerosis. Dietary flavonoids are thought to protect against the disease by exerting hypocholesterolemic effects. However, clinical studies are not conclusive enough to provide the supporting evidence. Recent clinical studies on both normo- and hypercholesterolemic subjects with different flavonoids sources lasting 1-13... 

Prasad, K. 2005. Hypocholesterolemic and antiatherosclerotic effect of flax lignan complex isolated from flaxseed. Atherosclerosis 179, 269-275. 

Seetharamaiah, G.S. and Chandrasekharan, S. 1989. Studies on hypocholesterolemic activity of rice bran oil. Atherosclerosis 78, 219-223. 

F Hirata, KFujita, Y Ishikura, KHosoda, TIshikawa, H Nakamura. Hypocholesterolemic effect of sesame lignan in humam. Atherosclerosis 122 135-136, 1996. 

Ramirez-Tortosa, M.C., Mesa, M.D., Aguilera, M.C., Quiles, J.L., Baro, L., Ramirez-Tortosa, C.L., Martinez-Victoria, E., and Gil, A., Oral administration of a turmeric extract inhibits LDL oxidation and has hypocholesterolemic effects in rabbits with experimental atherosclerosis. Atherosclerosis, 147 (2), 371-378,1999. 

Hypercholesterolemia. Diet has long been considered to play an important role in hypercholesterolemia and atherosclerosis, but most of the emphasis has been on dietary fat and cholesterol. Several clinical and experimental studies demonstrate that replacement in the diet of animal protein with soy protein had a striking hypocholesterolemic effect (74,75). 

Kurushima, H., Hayashi, K., Toyota, Y, Kambe, M., and Ka-jiyama, G. (1995) Comparison of Hypocholesterolemic Effects Induced by Dietary Linoleic Acid and Oleic Acid in Hamsters, Atherosclerosis 114, 213-221. 

Kurmukov AG, Aizikov MI, Rasulova SA, Makhmudov OKh (1986) Hypolipidemic, hypocholesterolemic and antisclerotic effects of the rotenoid glycoside amorphine. Farmakol Toksikol 49(6) 54-57 Kurmukov AG, Aizikov MI, Rasulova SA, Sidiakin GP, Sham ianov ID, Malikov VM (1991a) The angioprotector and hypolipidemic activity of leucomisine on experimental atherosclerosis. Farmakol Toksikol 54(3) 35-37 (in Russian)... 

Carew, T.E., Schwenke, D.C., and Steinberg, D. (1987) Antiatherogenic Effect of Probucol Unrelated to Its Hypocholesterolemic Effect Evidence That Antioxidants In Vivo Can Selectively Inhibit Low Density Lipoprotein Degradation in Macrophage-Rich Fatty Streaks and Slow the Progression of Atherosclerosis in the Watanabe Heritable Hyperlipidemic Rabbits, Proc. Natl. Acad. Sci. USA 84, 7725-7729. 

Cholesterol esterase (CEase) plays important roles in the hydrolysis of sterol esters. This enzyme has stimulated research interest as a target in atherosclerosis and for the development of hypocholesterolemic agents since the 1990s. Peng and coworkers developed the synthesis ofphosphaisocoumarins and investigated these compounds as potential inhibitors of pancreatic cholesterol esterase (CEase) (10EJMC1955). 

Phytosterols (PS) are plant sterols and stanols widely distributed in plant sources that resemble cholesterol in terms of structure and physiological functions. The cholesterol-lowering capacity of PS is well documented in animal and human studies. However, recent studies suggest that the beneficial effects of PS are not only limited to their hypocholesterolemic capacity as they can also act as immunomodulatory, anti-inflammatory, and antidiabetic agents. Further, there is a growing body of evidence which supports that they play an important role in the prevention of other diseases such as cancer and atherosclerosis. Nevertheless, the mechanisms by which PS exert their beneficial functions, the physiological relevance of PS, and their potential adverse effects are not yet fully understood. Therefore, the main aim of this chapter is to provide a contemporaneous overview of the beneficial properties of PS, their mechanism of action, and safety. 

Saponins derived from the root of the plant have shown hypocholesterolemic activity in monkeys on a high cholesterol diet (also see quillaia) Male rats fed a complex of alfalfa top saponins (1% of diet for 6 months) showed reduced levels of serum cholesterol and triglycerides, with no evidence of toxicity. Alfalfa top saponins have also shown hypocholesterolemic activity and prevention of atherosclerosis. ... 

Hirata, F, Fujita, K, Ishikura, Y, Hosoda, K, Ishikawa, T and Nakamura, H (1996) Hypocholesterolemic effect of sesame lignan in humans. Atherosclerosis, 122, 135-136. 

Other compounds that have been reported to have hypocholesterolemic properties in humans include Metrazol, D-thyroxine, erythritol plus tetranicotinate, 3-hydroxy-3-methylglutaric acid, aminazine, neomycin, phenindione 17-(3-hydroxy-l-propyTiyl)-3-methoxyestra-l,3,5, (10)-trien-17B-ol,17a-hydrocinnamate, Fradiomycin.Metamucil, an oral hydrophilic colloid, and cholestyramine " lowered serum cholesterol and Increased bile acid excretion. Several series of compounds with members having serum cholesterol lowering possibilities have been prepared. Further investigation of several of the individual compounds may show whether or not they are effective against atherosclerosis. 

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