A novel alkaloid antioxidant, Boldine and synthetic antioxidant, reduced form of RU486, inhibit the oxidation of LDL in-vitro and atherosclerosis in vivo in LDLR(-/-) mice.
A corollary to the oxidation hypothesis of atherosclerosis is that the consumption of antioxidants is beneficial. However, the literature is divided in support of this conclusion. In this study, Boldine, an alkaloid of Peumus boldus and reduced form of RU486, was tested for their antioxidant potency both in, in vitro oxidation system and in mouse models. Boldine decreased the ex-vivo oxidation of low-density lipoprotein (LDL). Two different in vivo studies were performed to study the effect of these compounds on the atherosclerotic lesion formation in LDLR(-/-) mice. In study I, three groups of LDLR(-/-) mice (N = 12 each) were fed an atherogenic diet. Group 1 was given vehicle and group 2 and 3 were given 1mg of Boldine or Red RU per day for 12 weeks. In study II, two groups of LDLR(-/-) mice N = 10 each) were fed an atherogenic diet. Group 1 was given vehicle and group 2 was given 5mg of Boldine per day. The results indicated that there was a decrease in lesion formation reaching a 40% reduction due to Boldine and 45% reduction by Red RU compared to controls. The in vivo tolerance of Boldine in humans (has been used as an herbal medicine in other diseases) should make it an attractive alternative to Vitamin E.
Santanam
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N
Department of Pathology, LSU Health Science Center, 533 Bolivar St, New Oreleans, LA 70112, USA.
Penumetcha
M
M
Speisky
H
H
Parthasarathy
S
S
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001060:Aporphines / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015735:Mifepristone / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects*; D011336:Probability; D012016:Reference Values; D012680:Sensitivity and Specificity
D000975:Antioxidants; D001060:Aporphines; D008077:Lipoproteins, LDL; D015735:Mifepristone; C011686:boldine